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Sample records for binding globulin shbg

  1. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

  2. Sex hormone-binding globulin (SHBG expression in ovarian carcinomas and its clinicopathological associations.

    Directory of Open Access Journals (Sweden)

    Ruixia Huang

    Full Text Available Sex hormone-binding globulin (SHBG is known as a carrier protein. It is classically thought to be mainly synthesized in the liver and then secreted into the circulating system, where it binds to sex steroids with a high affinity and modulates the bio-availability of the hormones. Other organs known to produce SHBG include brain, uterus, testis, prostate, breast and ovary, and the local expressed SHBG may play an important role in tumor development. However, SHBG expression status and its clinicopathological significance in ovarian cancer cells are not reported yet. In our present study, we examined and found the variable SHBG expression in four ovarian cancer cell lines (OV-90, OVCAR-3, SKOV-3 and ES-2 by immunocytochemistry and Western blotting. We then extended our study to 248 ovarian carcinoma samples, which were collected at The Norwegian Radium Hospital, Oslo University Hospital with complete clinical information, and discovered that SHBG was variably expressed in these ovarian carcinomas. Higher level of SHBG expression was significantly associated with more aggressive histological subtype (p = 0.022, higher FIGO stage (p = 0.018 and higher histological grade (grade of differentiation, p = 0.020, although association between SHBG expression and OS/PFS was not observed. Our results demonstrate that ovarian cancer cells produce SHBG and higher SHBG expression in ovarian carcinoma is associated with unfavorable clinicopathological features.

  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

    2009-01-01

    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...... used data from this SNP, or closely correlated SNPs, in 27 657 type 2 diabetes patients and 58 481 controls from 15 studies. We then used data from additional studies to estimate the difference in SHBG levels between type 2 diabetes patients and controls. The SHBG SNP rs1799941 was associated with type...... 2 diabetes [odds ratio (OR) 0.94, 95% CI: 0.91, 0.97; P = 2 x 10(-5)], with the SHBG raising allele associated with reduced risk of type 2 diabetes. This effect was very similar to that expected (OR 0.92, 95% CI: 0.88, 0.96), given the SHBG-SNP versus SHBG levels association (SHBG levels are 0.2...

  5. Sex-hormone binding globulin (SHBG) levels during pregnancy as predictors for pre-eclampsia and fetal growth restriction

    OpenAIRE

    Valdés R, Enrique; Lattes A, Karina; Muñoz S, Hernán; Ángel Cumsille, Miguel

    2012-01-01

    Background: Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). Aim: To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Patients and Methods: Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselectedpregnant wome...

  6. Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG).

    Science.gov (United States)

    Schöttner, M; Gansser, D; Spiteller, G

    1997-12-01

    Polar extracts of the stinging nettle (Urtica dioica L.) roots contain the ligans (+)-neoolivil, (-)-secoisolariciresinol, dehydrodiconiferyl alcohol, isolariciresinol, pinoresinol, and 3,4-divanillyltetrahydrofuran. These compounds were either isolated from Urtica roots, or obtained semisynthetically. Their affinity to human sex hormone binding globulin (SHBG) was tested in an in vitro assay. In addition, the main intestinal transformation products of plant lignans in humans, enterodiol and enterolactone, together with enterofuran were checked for their activity. All lignans except (-)-pinoresinol developed a binding affinity to SHBG in the in vitro assay. The affinity of (-)-3,4-divanillyltetrahydrofuran was outstandingly high. These findings are discussed with respect to potential beneficial effects of plant lignans on benign prostatic hyperplasia (BPH).

  7. [Sex-hormone binding globulin (SHBG) levels during pregnancy as predictors for pre-eclampsia and fetal growth restriction].

    Science.gov (United States)

    Valdés R, Enrique; Lattes A, Karina; Muñoz S, Hernán; Cumsille, Miguel Angel

    2012-05-01

    Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselected pregnant women during routine 11-14 week and 22-25 week ultrasound examinations, conforming two different study groups. Posteriorly, serum SHBG concentrations were determined in women who developed Pre-eclampsia, RCIU and their respective controls. Fifty five patients were included in the 11-14 weeks group. Nine women that developed PE, 10 that developed RCIU and 36 controls were selected from this group. There were no significant differences in SHBG levels between patients with PE, RCIU or controls (324.7 (26.6), 336.8 (33.9) and 377.5 (24.3) nmol/L, respectively). Fifty four women were included in the 22-25 weeks group. Eight women who developed Pre-eclampsia, 15 who developed RCIU and 31 controls were selected. Again, there were no significant differences in SHBG levels between patients with PE, RCIU or controls (345.5 (151.1), 383.8 (143.4) and 345.5 nmol/l (151.1), respectively). Maternal SHBG serum levels did not predict subsequent development of Pre-eclampsia and RCIU.

  8. 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....

  9. Effect of triiodothyronine (L-T/sub 3/) and weight loss on sex-hormone binding globulin (SHBG) in hirsute obese women

    Energy Technology Data Exchange (ETDEWEB)

    Cavaliere, H.; Medeiros Neto, G.A. (Sao Paulo Univ. (Brazil). Faculdade de Medicina)

    1984-06-01

    The effect of a 60-day period of treatment with L-T/sub 3/ (200 ..mu..g/day) was evaluated in hirsute obese women and normal controls. The obese patients were also submitted to a low calorie high protein diet. Mean initial weight significantly declined with a significant lowering of the mean DHEA-S level. There were changes in serum T/sub 3/ which rose in both obese and normal patients. Serum sex-hormone binding globulin levels at baseline studies were significantly higher in normal controls than in obese patients. At the end of the 60-day period of L-T/sub 3/ administration it was observed in both groups a 2-4 fold increase in serum SHBG levels but normal controls had significantly higher mean values than obese individuals.

  10. The effect of triiodothyronine (L-T3) and weight loss on sex-hormone binding globulin (SHBG) in hirsute obese women

    International Nuclear Information System (INIS)

    Cavaliere, H.; Medeiros Neto, G.A.

    1984-01-01

    The effect of a 60-day period of treatment with L-T 3 (200 μg/day) was evaluated in hirsute obese women and normal controls. The obese patients were also submitted to a low calorie high protein. Mean initial weight significantly declined with a significant lowering of the mean DHEA-S leves. There was changes in serum T 3 rose in both obese and normal patients. Serum sex-hormone binding globulin levels at baseline studies were significantly higher in normal controls than in obese patients. At the end of de 60-day period of L-T 3 administration it was observed in both groups a 2-4 fold increase in serum SHBG levels but normal controls had significantly higher mean values than obese individuals. (M.A.C.) [pt

  11. Autocrine and Paracrine Control of Breast Cancer Growth by Sex Hormone-Binding Globulin

    National Research Council Canada - National Science Library

    Rosner, Wiliam

    2003-01-01

    We propose that the expression of Sex Hormone-Binding Globulin (SHBG) by breast cancer cells is biologically regulated and that this SHBG functions to alter the effects of estrogens within the breast cancer cell...

  12. Autocine and Paracrine Control of Breast Cancer Growth by Sex Hormone-Binding Globulin

    National Research Council Canada - National Science Library

    Rosner, William

    2004-01-01

    We propose that the expression of Sex Hormone-Binding Globulin (SHBG) by breast cancer cells is biologically regulated and this SHBG functions to alter the effects of estrogens within the breast cancer cell...

  13. Modulation of SHBG binding to testosterone and estradiol by sex and morbid obesity.

    Science.gov (United States)

    Grasa, María Del Mar; Gulfo, José; Camps, Núria; Alcalá, Rosa; Monserrat, Laura; Moreno-Navarrete, José María; Ortega, Francisco José; Esteve, Montserrat; Remesar, Xavier; Fernández-López, José Antonio; Fernández-Real, José Manuel; Alemany, Marià

    2017-04-01

    Sex hormone-binding globulin (SHBG) binds and transports testosterone and estradiol in plasma. The possibility that SHBG is a mixture of transporting proteins has been postulated. We analyzed in parallel the effects of obesity status on the levels and binding capacity of circulating SHBG and their relationship with testosterone and estradiol. Anthropometric measures and plasma were obtained from apparently healthy young (i.e. 35 ± 7 years) premenopausal women ( n =  32) and men ( n =  30), with normal weight and obesity (BMI >30 kg/m 2 ). SHBG protein (Western blot), as well as the plasma levels of testosterone, estradiol, cortisol and insulin (ELISA) were measured. Specific binding of estradiol and testosterone to plasma SHBG was analyzed using tritium-labeled hormones. Significant differences in SHBG were observed within the obesity status and gender, with discordant patterns of change in testosterone and estradiol. In men, testosterone occupied most of the binding sites. Estrogen binding was much lower in all subjects. Lower SHBG of morbidly obese (BMI >40 kg/m 2 ) subjects affected testosterone but not estradiol. The ratio of binding sites to SHBG protein levels was constant for testosterone, but not for estradiol. The influence of gender was maximal in morbid obesity, with men showing the highest binding / SHBG ratios. The results reported here are compatible with SHBG being a mixture of at least two functionally different hormone-binding globulins, being affected by obesity and gender and showing different structure, affinities for testosterone and estradiol and also different immunoreactivity. © 2017 European Society of Endocrinology.

  14. Effect of anticonvulsants on plasma testosterone and sex hormone binding globulin levels.

    Science.gov (United States)

    Barragry, J M; Makin, H L; Trafford, D J; Scott, D F

    1978-01-01

    Plasma sex hormone binding globulin (SHBG) and testosterone levels were measured in 29 patients with epilepsy (16 men and 13 women), most of them on chronic therapy with anticonvulsant drugs. Sex hormone binding globulin concentrations were increased in both sexes and testosterone levels in male patients. It is postulated that anticonvulsants may induce hepatic synthesis of SHBG. PMID:569688

  15. 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 glucose metabolism and metabolic risk during puberty....

  16. In silico identification of anthropogenic chemicals as ligands of zebrafish sex hormone binding globulin

    International Nuclear Information System (INIS)

    Thorsteinson, Nels; Ban, Fuqiang; Santos-Filho, Osvaldo; Tabaei, Seyed M.H.; Miguel-Queralt, Solange; Underhill, Caroline; Cherkasov, Artem; Hammond, Geoffrey L.

    2009-01-01

    Anthropogenic compounds with the capacity to interact with the steroid-binding site of sex hormone binding globulin (SHBG) pose health risks to humans and other vertebrates including fish. Building on studies of human SHBG, we have applied in silico drug discovery methods to identify potential binders for SHBG in zebrafish (Danio rerio) as a model aquatic organism. Computational methods, including; homology modeling, molecular dynamics simulations, virtual screening, and 3D QSAR analysis, successfully identified 6 non-steroidal substances from the ZINC chemical database that bind to zebrafish SHBG (zfSHBG) with low-micromolar to nanomolar affinities, as determined by a competitive ligand-binding assay. We also screened 80,000 commercial substances listed by the European Chemicals Bureau and Environment Canada, and 6 non-steroidal hits from this in silico screen were tested experimentally for zfSHBG binding. All 6 of these compounds displaced the [ 3 H]5α-dihydrotestosterone used as labeled ligand in the zfSHBG screening assay when tested at a 33 μM concentration, and 3 of them (hexestrol, 4-tert-octylcatechol, and dihydrobenzo(a)pyren-7(8H)-one) bind to zfSHBG in the micromolar range. The study demonstrates the feasibility of large-scale in silico screening of anthropogenic compounds that may disrupt or highjack functionally important protein:ligand interactions. Such studies could increase the awareness of hazards posed by existing commercial chemicals at relatively low cost

  17. Sex hormone binding globulin, free estradiol index, and lipid profiles in girls with precocious puberty

    Directory of Open Access Journals (Sweden)

    Hyun-Wook Chae

    2013-06-01

    Full Text Available PurposeSex hormone-binding globulin (SHBG modulates the availability of biologically active free sex hormones. The regulatory role of SHBG might be important in the relationship between hormone levels and the modification of lipid profiles in girls with precocious puberty. However, few studies have evaluated the relationship of SHBG, free estradiol index (FEI, and lipid levels in these girls.MethodsOne hundred and nine girls less than 8 years of age with pubertal development were enrolled. FEI was calculated with SHBG and estradiol (E2. We analyzed SHBG between peak luteinizing hormone (LH≥5 (IU/L (group 1 and LH<5 (IU/L (group 2 through a gonadotropin releasing hormone stimulation test.ResultsBody mass index (BMI standard deviation score (SDS was higher in group 2 than in group 1 (P=0.004. Serum SHBG levels did not differ and FEI was not higher in group 1 (P=0.122. Serum cholesterol, HDL, and LDL did not differ; however, triglyceride levels were higher in group 2 (P=0.023. SHBG was negatively correlated with bone age advancement, BMI, BMI SDS, and FEI, and was positively correlated with HDL. However, SHBG was not correlated with E2 or peak LH.ConclusionSerum SHBG itself might not be associated with precocious puberty in girls, but it might be related to BMI and lipid profiles. Further studies are needed to reveal the relationship between sex hormone and obesity in girls with precocious puberty.

  18. 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...

  19. Sex hormone binding globulin - an important biomarker for predicting PCOS risk: A systematic review and meta-analysis.

    Science.gov (United States)

    Deswal, Ritu; Yadav, Arun; Dang, Amita Suneja

    2018-02-01

    Sex hormone-binding globulin (SHBG) is a glycoprotein which regulates bioavailability of sex steroid hormones. Interest in SHBG has escalated in recent years because of its inverse association with polycystic ovary syndrome (PCOS), obesity, insulin resistance, metabolic syndrome, and diabetes type II. This meta-analysis was performed to examine the associations of SHBG with PCOS and to correlate serum SHBG levels with various PCOS associated endocrine and metabolic dysregulation as well as to determine the effects of various therapeutic agents on serum SHBG levels in PCOS patients in order to assess the true accuracy of SHBG in the prediction of PCOS. A literature search was performed using Pub-Med, Science direct, google scholar, EMBASE, and Cochrane library. A total of 675 relevant records were identified, of which 62 articles were included. Meta-analysis using a random-effects model was performed using STATA version 13 to calculate standardized mean difference (SMD) with 95% confidence intervals (95 % CIs). SHBG levels in controls were significantly higher than that of PCOS patients (SMD= -0.83, 95%CI = -1.01, -0.64), with significant heterogeneity across studies (I 2 = 93.9% and p=0.000). Our results suggest that the lower serum SHBG levels are associated with the risk of PCOS. SHBG may also play an important role in various metabolic disturbances in PCOS patients. Therapeutic interventions improved SHBG levels in PCOS women which further reduced PCOS associated complications. Therefore, SHBG levels may prove to be a useful biomarker for the diagnosis and treatment of PCOS. Systematic review registration: PROSPERO CRD42017057972 Abbreviations: PCOS: polycystic ovary syndrome; SHBG: sex hormone-binding globulin.

  20. Human sex hormone-binding globulin gene expression- multiple promoters and complex alternative splicing

    Directory of Open Access Journals (Sweden)

    Rosner William

    2009-05-01

    Full Text Available Abstract Background Human sex hormone-binding globulin (SHBG regulates free sex steroid concentrations in plasma and modulates rapid, membrane based steroid signaling. SHBG is encoded by an eight exon-long transcript whose expression is regulated by a downstream promoter (PL. The SHBG gene was previously shown to express a second major transcript of unknown function, derived from an upstream promoter (PT, and two minor transcripts. Results We report that transcriptional expression of the human SHBG gene is far more complex than previously described. PL and PT direct the expression of at least six independent transcripts each, resulting from alternative splicing of exons 4, 5, 6, and/or 7. We mapped two transcriptional start sites downstream of PL and PT, and present evidence for a third SHBG gene promoter (PN within the neighboring FXR2 gene; PN regulates the expression of at least seven independent SHBG gene transcripts, each possessing a novel, 164-nt first exon (1N. Transcriptional expression patterns were generated for human prostate, breast, testis, liver, and brain, and the LNCaP, MCF-7, and HepG2 cell lines. Each expresses the SHBG transcript, albeit in varying abundance. Alternative splicing was more pronounced in the cancer cell lines. PL- PT- and PN-derived transcripts were most abundant in liver, testis, and prostate, respectively. Initial findings reveal the existence of a smaller immunoreactive SHBG species in LNCaP, MCF-7, and HepG2 cells. Conclusion These results extend our understanding of human SHBG gene transcription, and raise new and important questions regarding the role of novel alternatively spliced transcripts, their function in hormonally responsive tissues including the breast and prostate, and the role that aberrant SHBG gene expression may play in cancer.

  1. The association between sex hormone-binding globulin and type 2 diabetes in Nigerian men

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    Fayefori M. Abbiyesuku

    2013-07-01

    Full Text Available Background: Epidemiological studies have shown that sex hormone-binding globulin (SHBG has a role in glucose homeostasis in both men and women. However, a prospective study on Japanese-American subjects concluded that SHBG was not a significant risk factor in either men or women, suggesting ethnic differences. We were not aware of any evaluation of SHBG in subjects of African ancestry. Objectives: We investigated the association between SHBG and insulin resistance in type 2 diabetic diabetic men in a hospital in Nigeria. Method: Forty-eight male subjects with type 2 diabetes and 20 non-diabetic male subjects were recruited in this cross-sectional hospital-based study by the convenient sampling method.Height and circumferences around the waist and hip were measured to the nearest 0.5 cm and the waist–hip ratio was calculated from this measurement. Weight was measured and body mass index was calculated. Fasting plasma glucose concentration was measured by the glucose oxidase method with a between-run coefficient of variation of 3%. Insulin and SHBG were measured by means of enzyme-linked immunosorbent assay (ELISA. Results: There was a statistically-significant difference between test results for the diabetic and non-diabetic patients. The mean SHBG concentration was higher in the non-diabetic group (42.2 nmol/L than the diabetic group (30.5 nmol/L. A significant inverse association between insulin resistance and SHBG was observed (r = 0.353, p < 0.015. Conclusion: This study supported earlier observations that a significant inverse correlation exists between SHBG and insulin resistance and provides evidence that the relationship may extend to type 2 diabetic men of African ancestry in Nigeria.

  2. [Influence of water fluoride exposure on sex hormone binding globulin and testosterone in adult male].

    Science.gov (United States)

    Zhou, Tong; Yang, Rupu; Li, Shihong; Zheng, Guoqing; Xi, Yu; Cheng, Xuemin; Hou, Jiaxiang; Cui, Liuxin; Ba, Yue

    2013-03-01

    To explore the influence of water fluoride exposure on sex hormone binding globulin (SHBG) and testosterone in adult male. Cross-sectional study was conducted in three villages of Tongxu county including high fluoride group (HFG), defluoridation project group (DFPG) and control group (CG) based on the fluoride concentration in drinking water. Adult male who were born and raised in the village and aged 18 - 50 years old were recruited using cluster sampling. Fasting blood and morning urine samples were collected. The fluoride levels in drinking water and urine were detected by fluoride-ion selective electrode method. Serum SHBG level was determined using enzyme-linked immunosorbent assay (ELISA). The chemical luminescence immune analysis method was used to detect serum testosterone content. Serum SHBG level was 47.85 nmol/L in CG, 31.37 nmol/L in DFPG and 24.52 nmol/L in HFG respectively. There were significant difference among of three groups (P < 0.05). Serum testosterone level was 3.69 ng/ml in CG, 4.61 ng/ml in DFPG and 4.83 ng/ml in HFG respectively. Serum testosterone level in HFG was significantly higher than that in CG (P < 0.05). Serum SHBG level in HFG has positive correlation with serum testosterone (r = 0.230, P = 0.049), which has not been observed in DFPG and CG. Long-time fluorine exposure may affect serum SHBG and testosterone level in adult male.

  3. Relation of cigarette smoking in males of different ages to sex hormone binding globulin and testosterone

    International Nuclear Information System (INIS)

    El-Nabarawy, F.S.

    2002-01-01

    The relationship of cigarette smoking, age, total testosterone free testosterone and sex hormone binding globulin (SHBG) were examined by solid phase radioimmunoassay in 90 randomly chosen healthy males of different ages. The serum levels of these hormones were investigated for smokers compared with non-smokers, of the same ages in 3 groups (adolescent males, middle aged males, and old aged males). Results indicated that cigarette smokers showed increased serum levels of testosterone (60.0% higher, P> 0.05), free testosterone (51.0 higher, P > 0.005) in young adolescent males group, testosterone (27.8% higher, P > 0.001), free testosterone (21.3% higher, P > 0.001) in middle aged males group, and testosterone (21.0% higher, P > 0.001), free testosterone (16.8% higher, P > 0.4) in old ages males group. SHBG was calculated as a mean of free and total testosterone in each group. smokers showed higher mean values of SHBG than non-smokers. Age was positively associated with serum SHBG, it was found that SHBG increased by 17.2% from the youngest (> 18 years) to the oldest age (> 65 years)

  4. Low Levels of Sex Hormone-Binding Globulin Constitute an Independent Risk Factor for Arterial Stiffness in Korean Women

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    Kunhee Han

    2017-01-01

    Full Text Available The association between sex hormone-binding globulin (SHBG and arterial stiffness in women is not conclusive. In addition, obesity might also be involved in the relationship between SHBG and atherosclerosis. The aim of this study was to determine the relationship between SHBG and arterial stiffness in association with central obesity in women. This cross-sectional study included 381 women who participated in the health checkup programs in one hospital. The brachial-ankle pulse wave velocity (baPWV was measured as a marker for arterial stiffness. A negative correlation was observed between SHBG levels and baPWV (rho = −0.281. The relationship was significant even after adjusting for potential confounders (beta = −0.087 in fully adjusted model. After considering the interaction between central obesity and SHBG levels, the significant association was evident only in obese women (P for interaction = 0.025. Adjustment for a 10-year atherosclerotic cardiovascular disease (ASCVD risk scores, instead of each cardiovascular risk factor individually, did not affect the significance of the relationship between SHBG levels and baPWV. Serum levels of SHBG were negatively associated with arterial stiffness independent of cardiovascular risk factors or 10-year ASCVD risk scores in Korean women. The relationship may be potentiated by central obesity.

  5. Characterization of mini-protein S, a recombinant variant of protein S that lacks the sex hormone binding globulin-like domain

    NARCIS (Netherlands)

    van Wijnen, M.; Stam, J. G.; Chang, G. T.; Meijers, J. C.; Reitsma, P. H.; Bertina, R. M.; Bouma, B. N.

    1998-01-01

    Protein S is a vitamin K-dependent glycoprotein involved in the regulation of the anticoagulant activity of activated protein C (APC). Also, an anticoagulant role for protein S, independent of APC, has been described. Protein S has a unique C-terminal sex hormone binding globulin (SHBG)-like domain

  6. A portion of heifers attaining “early puberty” do not display estrus, are anovulatory and have altered sex hormone binding globulin concentrations

    Science.gov (United States)

    Cows with excess androstenedione (High A4) in the follicular fluid of dominant follicles attain puberty earlier than their low androstenedione counterparts. Furthermore, High A4 cows are anovulatory (chronic or sporadic) and have lower Sex Hormone Binding Globulin (SHBG) compared to Low A4 ovulator...

  7. Sex Hormone–Binding Globulin and Risk of Type 2 Diabetes in Women and Men

    Science.gov (United States)

    Ding, Eric L.; Song, Yiqing; Manson, JoAnn E.; Hunter, David J.; Lee, Cathy C.; Rifai, Nader; Buring, Julie E.; Gaziano, J. Michael; Liu, Simin

    2009-01-01

    BACKGROUND Circulating sex hormone–binding globulin levels are inversely associated with insulin resistance, but whether these levels can predict the risk of developing type 2 diabetes is uncertain. METHODS We performed a nested case–control study of postmenopausal women in the Women’s Health Study who were not using hormone therapy (359 with newly diagnosed type 2 diabetes and 359 controls). Plasma levels of sex hormone–binding globulin were measured; two polymorphisms of the gene encoding sex hormone–binding globulin, SHBG, that were robustly associated with the protein levels were genotyped and applied in mendelian randomization analyses. We then conducted a replication study in an independent cohort of men from the Physicians’ Health Study II (170 with newly diagnosed type 2 diabetes and 170 controls). RESULTS Among women, higher plasma levels of sex hormone–binding globulin were prospectively associated with a lower risk of type 2 diabetes: multivariable odds ratios were 1.00 for the first (lowest) quartile of plasma levels, 0.16 (95% confidence interval [CI], 0.08 to 0.33) for the second quartile, 0.04 (95% CI, 0.01 to 0.12) for the third quartile, and 0.09 (95% CI, 0.03 to 0.21) for the fourth (highest) quartile (P<0.001 for trend). These prospective associations were replicated among men (odds ratio for the highest quartile of plasma levels vs. the lowest quartile, 0.10; 95% CI, 0.03 to 0.36; P<0.001 for trend). As compared with homozygotes of the respective wild-type allele, carriers of a variant allele of the SHBG single-nucleotide polymorphism (SNP) rs6259 had 10% higher sex hormone–binding globulin levels (P = 0.005), and carriers of an rs6257 variant had 10% lower plasma levels (P = 0.004); variants of both SNPs were also associated with a risk of type 2 diabetes in directions corresponding to their associated sex hormone–binding globulin levels. In mendelian randomization analyses, the predicted odds ratio of type 2 diabetes per

  8. Low Sex Hormone-Binding Globulin Levels Associate with Prediabetes in Chinese Men Independent of Total Testosterone

    Science.gov (United States)

    Han, Bing; Li, Qin; Chen, Yi; Zhu, Chunfang; Chen, Yingchao; Xia, Fangzhen; Cang, Zhen; Lu, Meng; Chen, Chi; Lin, Dongping; Lu, Yingli

    2016-01-01

    Objective The association ns between prediabetes and androgens have been rarely reported, especially in Chinese men. We aimed to investigate whether androgens were associated with the prevalence of prediabetes diagnosed with new American Diabetes Association criteria in Chinese men and then to assess which androgen value was the most relevant factor. Methods A total of 2654 men (52.6±13.4 years old) were selected. Serum total testosterone (TT), sex hormone-binding globulin (SHBG) and free testosterone (FT) were measured. Covariance analysis of different androgen values were performed in age subgroups. Multinomial logistic regression was used for the association of TT, SHBG and FT with prediabetes and diabetes, as well as prediabetes in age subgroups. Results According to ADA new criteria, normoglycemia, prediabetes, and diabetes were diagnosed in 1405, 907 and 342 men, respectively. In covariance analysis, SHBG of prediabetes were found lower than that of normoglycemia but higher than that of diabetes (P prediabetes and diabetes. While, after full adjustment for age, residence area, economic status, waist circumference, metabolic factors, other two androgen values and HOMA-IR, only the associations of SHBG with prevalence of prediabetes and diabetes persisted statistically significant, especially in the elderly with prediabetes (all P for trend prediabetes and diabetes in Chinese men. Low serum SHBG was the most relevant factor for prediabetes and diabetes. Whether it is an independent predictor for incident prediabetes in Chinese men needs further explorations. PMID:27583401

  9. Endogenous Androgens and Sex Hormone-Binding Globulin in Women and Risk of Metabolic Syndrome and Type 2 Diabetes.

    Science.gov (United States)

    Fenske, Benjamin; Kische, Hanna; Gross, Stefan; Wallaschofski, Henri; Völzke, Henry; Dörr, Marcus; Nauck, Matthias; Keevil, Brian G; Brabant, Georg; Haring, Robin

    2015-12-01

    The association of endogenous androgens and sex hormone-binding globulin (SHBG) with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) mostly 23562 refers to small and selected study samples with immunoassay-based measurements. Thus, we investigated the association of hormone levels with MetS and T2DM in women from a large population-based sample. A total of 2077 women from the Study of Health in Pomerania were assessed at baseline (N = 3160, 1997-2001) and 5-year follow-up (N = 1711, 2002-2006). We investigated associations of total testosterone (T) and androstenedione measured by liquid chromatography-tandem mass spectrometry, SHBG by immunoassay, and free T and free androgen index with MetS and T2DM. Baseline prevalence of MetS and T2DM was 23.1% (N = 365) and 9.5% (N = 196), with an incidence of 17.7 and 7.0 per 1.000 person-years, respectively. Cross-sectional analyses yielded inverse associations of SHBG with MetS (relative risk [RR], 0.67; 95% confidence interval [CI], 0.60-0.74) and T2DM (RR, 0.61; 95% CI, 0.50-0.74) after multivariable adjustment. In longitudinal analyses, only age-adjusted models showed an inverse association of baseline SHBG with incident MetS (RR, 0.61; 95% CI, 0.51-0.73) and T2DM (RR, 0.58; 95% CI, 0.43-0.78). Multivariable-adjusted models stratified by menopausal status revealed an inverse association between SHBG and incident MetS risk in postmenopausal women (RR, 0.65; 95% CI, 0.51-0.81). This longitudinal population-based study revealed independent inverse associations of SHBG with MetS and T2DM, suggesting low SHBG as a potential risk marker for cardiometabolic morbidity, especially among postmenopausal women.

  10. Association of Serum Testosterone and Sex Hormone Binding Globulin Levels in Females with Acne Based on its Severity

    International Nuclear Information System (INIS)

    Kiayani, A. J.; Rehman, R. U.

    2016-01-01

    Background: Androgens are involved in the development of acne. The aim of this study was to find out if there was an association of serum testosterone and sex hormone binding globulin (SHBG) in females with acne based on its severity. Methods: It was a cross sectional study, conducted in Dermatology unit of Fauji Foundation Hospital (FFH), Rawalpindi. Duration of study was eight months. Adult females with acne were enrolled in the study. Patients were categorized into minor, mild, moderate groups. Blood samples were taken for serum testosterone and SHBG. Results: Five hundred and thirty-one adult female were enrolled into the study. The mean age was 21.49±4.73 years. Acne was graded as minor in 78 (14.7 percent) cases, mild in 248 (46.7 percent) and moderate in 205 (38.6 percent). There was no statistically significant relationship between the levels of serum testosterone (p=0.776) and SHBG (p=0.711) with acne severity. Conclusion: There was no association of serum testosterone and sex hormone binding globulin levels in females with acne based on its severity. (author)

  11. Low Sex Hormone-Binding Globulin Levels Associate with Prediabetes in Chinese Men Independent of Total Testosterone.

    Directory of Open Access Journals (Sweden)

    Hui Zhu

    Full Text Available The association ns between prediabetes and androgens have been rarely reported, especially in Chinese men. We aimed to investigate whether androgens were associated with the prevalence of prediabetes diagnosed with new American Diabetes Association criteria in Chinese men and then to assess which androgen value was the most relevant factor.A total of 2654 men (52.6±13.4 years old were selected. Serum total testosterone (TT, sex hormone-binding globulin (SHBG and free testosterone (FT were measured. Covariance analysis of different androgen values were performed in age subgroups. Multinomial logistic regression was used for the association of TT, SHBG and FT with prediabetes and diabetes, as well as prediabetes in age subgroups.According to ADA new criteria, normoglycemia, prediabetes, and diabetes were diagnosed in 1405, 907 and 342 men, respectively. In covariance analysis, SHBG of prediabetes were found lower than that of normoglycemia but higher than that of diabetes (P <0.05. In multinomial logistic regression, serum TT and SHBG were inversely associated with prediabetes and diabetes. While, after full adjustment for age, residence area, economic status, waist circumference, metabolic factors, other two androgen values and HOMA-IR, only the associations of SHBG with prevalence of prediabetes and diabetes persisted statistically significant, especially in the elderly with prediabetes (all P for trend <0.05.Serum androgen was inversely associated with prediabetes and diabetes in Chinese men. Low serum SHBG was the most relevant factor for prediabetes and diabetes. Whether it is an independent predictor for incident prediabetes in Chinese men needs further explorations.

  12. 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.

  13. Genetics Home Reference: corticosteroid-binding globulin deficiency

    Science.gov (United States)

    ... There may also be other genetic or environmental factors that influence whether an affected individual is more likely to develop pain or fatigue. Learn more about the gene associated with corticosteroid-binding globulin deficiency SERPINA6 Related Information What is a gene? What is a ...

  14. Effects of aerobic exercise training on serum sex hormone binding globulin, body fat index, and metabolic syndrome factors in obese postmenopausal women.

    Science.gov (United States)

    Kim, Jong-Won; Kim, Do-Yeon

    2012-12-01

    The percentage of obese postmenopausal women with metabolic syndrome is rising, and physical factors associated with the metabolic syndrome prevalence or incidence are also rising, including high body mass index (BMI), visceral fat area (VFA), low plasma sex hormone-binding globulin (SHBG) levels, and low cardiorespiratory fitness. Therefore, we investigated the influence of aerobic exercise on SHBG, body fat index (BFI), and metabolic syndrome factors in obese postmenopausal Korean women. Thirty healthy postmenopausal, women aged 53.46 ± 2.4 years and with over 32% body fat, were randomly assigned to an aerobic exercise group (EX; n=15) or to a "nonexercise" control (Con; n=15) group. The primary outcome measurements were serum SHBG, lipid profiles, insulin levels, and metabolic syndrome factors. Secondary outcome measurements were body composition, VFA, blood pressure (BP), and homeostasis model assessment of insulin resistance (HOMA-IR). Posttraining body weight and BFI (Pmetabolic syndrome factors (Pexercise group but not in the control group. SHBG levels also showed a significant positive correlation with high-density lipoprotein cholesterol (HDL-C) and significant negative correlations withglucose, diastolic blood pressure, fat mass, BMI, and percent body fat (Pexercise improves body composition, SHBG, insulin levels, and metabolic syndrome factors. These findings suggest that in obesepostmenopausal Korean women, 16 weeks of aerobic exercise is effective for preventing the metabolic syndrome caused by obesity.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Sex differences, endogenous sex-hormone hormones, sex-hormone binding globulin, and exogenous disruptors in diabetes and related metabolic outcomes.

    Science.gov (United States)

    Liu, Simin; Sun, Qi

    2016-12-19

    In assessing clinical and pathophysiological development of type 2 diabetes (T2D), the critical role of the sex steroids axis is underappreciated, particularly concerning the sex-specific relationships with many relevant cardiometabolic outcomes. In this issue of the Journal of Diabetes, we provide a comprehensive overview of these significant associations of germline variants in the genes governing the sex steroid pathways, plasma levels of steroid hormones, and sex hormone-binding globulin (SHBG) with T2D risk that have been observed in many clinical and high-quality large prospective cohorts of men and women across ethnic populations. Together, this body of evidence indicates that sex steroids and SHBG should be routinely incorporated into clinical characterization of T2D patients, particularly in screening prediabetic patients, such as those with metabolic syndrome, using plasma levels of SHBG. Given that several germline mutations in the SHBG gene have also been directly related to both plasma concentrations of SHBG and clinical manifestation of T2D, targeting signals in the sex steroid axis, particularly SHBG, may have significant utility in the prediction and treatment of T2D. Further, many of the environmental endocrine disrupting chemicals may exert their potential adverse effects on cardiometabolic outcomes via either estrogenic or androgenic signaling pathways, highlighting the importance of using the sex steroids and SHBG as important biochemical markers in both clinical and population studies in studying sex-specific mechanisms in the pathogenesis of T2D and its complications, as well as the need to equitably allocate resources in studying both men and women. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Effects of intraperitoneal insulin versus subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus

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    M Boering

    2016-06-01

    Full Text Available Aims Elevated sex hormone-binding globulin (SHBG concentrations have been described in patients with type 1 diabetes mellitus (T1DM, probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII, or subcutaneous (SC, influences SHBG concentrations among T1DM patients. Methods Post hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (±13 years, diabetes duration 23 (±11 years, and hemoglobin A1c (HbA1c 8.7 (±1.1 (72 (±12 mmol/mol. As secondary outcomes, testosterone, 17-β-estradiol, luteinizing hormone (LH, and follicle-stimulating hormone (FSH were analyzed. Results Estimated mean change in SHBG was −10.3nmol/L (95% CI: −17.4, −3.2 during CIPII and 3.7nmol/L (95% CI: −12.0, 4.6 during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was −6.6nmol/L (95% CI: −17.5, 4.3; −12.7nmol/L (95% CI: −25.1, −0.4 for males and −1.7nmol/L (95% CI: −24.6, 21.1 for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; −15.8nmol/L (95% CI: −24.2, −7.5 and −8.3nmol/L (95% CI: −14.4, −2.2, respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2U/L (95% CI: 0.1, 2.2 among males. Conclusions SHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids.

  20. Association of the pituitary-testicular axis function and sex hormone-binding globulin with melatonin secretion in morbidly obese men

    International Nuclear Information System (INIS)

    Ostrowska, Z.; Buntner, B.; Marek, B.; Zwirska-Korczala, K.

    1995-01-01

    A possible relationship between melatonin (MEL) secretion and pituitary-testicular function as well as the circadian rhythmicity of serum MEL, lutropin (LH), folitropin (FSH), estradiol (E 2 ), total testosterone (T) and sex hormone-binding globulin (SHBG) were evaluated in 16 men with the primary obesity (body mass index - BMI > 43 kg/m 2 ; waist-to-hip circumference ratio - WHR > 1.0) and in 17 healthy volunteers with normal body weight. The mean 24-h MEL level was significantly higher in obese patients than in healthy control individuals. Moreover, all obese men showed some abnormalities of MEL circadian pattern such as decreased ratio between day and night MEL levels, abnormal secretory peaks during the light hours and lower interindividual variability for timing amplitude. Abnormal circadian variations of MEL were associated with reduced 24-h mean values of LH, FSH, T and SHBG, whereas E 2 levels were elevated. (author). 49 refs, 4 figs, 2 tabs

  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.......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...

  2. Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: an individual participant data meta-analysis of observational studies.

    Directory of Open Access Journals (Sweden)

    Judith S Brand

    Full Text Available 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.We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI and individual MetS components.Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE.Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men.We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT with MetS and its individual components. Multivariable adjusted odds ratios (ORs and hazard ratios (HRs were calculated and effect modification by age and BMI was studied.Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77, 1.73 (95% CI 1.62-1.85 and 1.46 (95% CI 1.36-1.57 for TT, SHBG and FT, respectively and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36, 1.44 (95% 1.30-1.60 and 1.14 (95% 1.01-1.28 for TT, SHBG and FT, respectively. Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension.Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.

  3. A simple ligand-binding assay for thyroxine-binding globulin on reusable Sephadex columns

    International Nuclear Information System (INIS)

    Bastomsky, C.H.; Kalloo, H.; Frenkel-Leith, D.B.; McGill Univ., Montreal, Quebec

    1977-01-01

    A method for the assay of thyroxine-binding globulin on reusable Sephadex G-25 columns is described. It depends upon elution by diluted iodothyronine-free serum of protein-bound [ 125 I]thyroxine from the columns under conditions where binding to thyroxine-binding prealbumin and albumin are abolished. It is simple, rapid and precise, and permits determinations inlarge numbers of samples. Values (mg/l; mean +- S.D.) were: normals 31.6+-5.4, hyperthyroid 28.3+-4.8, hypothyroid 40.6+-7.5, oral contraceptives 40.1+-6.8, pregnant 50.3+-5.4, cirrhotics 20.7+-4.3. Concentrations were reduced in serum heated at 56degC, while the uptake of [ 125 I]triiodothyronine was increased. There was a significant negative correlation between thyroxine-binding globulin concentration and triiodothyronine uptake in the heated serum samples and in euthyroid subjects

  4. The association of testosterone, sex hormone-binding globulin, and insulin-like growth factor-1 with bone parameters in Korean men aged 50 years or older.

    Science.gov (United States)

    Kim, Hye-Jung; Koo, Hyung Suk; Kim, Young-Sang; Kim, Moon Jong; Kim, Kwang-Min; Joo, Nam-Seok; Haam, Ji-Hee

    2017-11-01

    Testosterone and insulin-like growth factor-1 (IGF-1) are essential factors for the maintenance of bone health in men. However, the results for the association of testosterone and IGF-1 with bone parameters were not consistent in prior studies. We evaluated the relationship of testosterone, sex hormone-binding globulin (SHBG), and IGF-1 with bone mineral density (BMD) and bone turnover markers (BTMs) in Korean men. We enrolled 1227 men aged ≥50 years in this cross-sectional study. Serum levels of total testosterone (TT), SHBG, IGF-1, osteocalcin, and C-terminal cross-linking telopeptide of type I collagen (CTX) were measured. Free testosterone (FT) was calculated using Vermeulen's method. BMD was measured by dual-energy X-ray absorptiometry. TT level was not related to BMD or BTMs in the unadjusted model; however, after adjusting for SHBG and IGF-1, the association between TT and BTMs was significant (β = -0.139 for osteocalcin and β = -0.204 for CTX). SHBG levels were negatively associated with lumbar BMD, and positively associated with BTMs in all models. As SHBG level increased, the prevalence of osteopenia or osteoporosis defined by BMD significantly increased (OR of 1SD change, 1.24). IGF-1 levels were significantly related with BMD, but not with BTMs. Meanwhile, FT levels were positively associated with BMD and negatively associated with BTMs. In conclusion, SHBG levels were independently related with bone parameters and osteopenia in men aged ≥50 years. IGF-1 levels were positively associated with BMD, but not with BTMs. SHBG may play a role in regulating age-related bone loss in men after middle-age.

  5. 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

    Gc globulin is an important protein of the plasma actin-scavenger system. As such, it has been shown to bind free actin and prevent hypercoagulation and shock in patients with massive actin release resulting from severe tissue injuries. Treatment of such patients with Gc globulin could therefore...

  6. 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

      Gc globulin is an important protein of the plasma actin-scavenger system. As such, it has been shown to bind free actin and prevent hypercoagulation and shock in patients with massive actin release resulting from severe tissue injuries. Treatment of such patients with Gc globulin could therefore...

  7. 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. Copyright 2010 Elsevier Inc. All rights reserved.

  8. SHBG is an important factor in stemness induction of cells by DHT in vitro and associated with poor clinical features of prostate carcinomas.

    Science.gov (United States)

    Ma, Yuanyuan; Liang, Dongming; Liu, Jian; Wen, Jian-Guo; Servoll, Einar; Waaler, Gudmund; Sæter, Thorstein; Axcrona, Karol; Vlatkovic, Ljiljana; Axcrona, Ulrika; Paus, Elisabeth; Yang, Yue; Zhang, Zhiqian; Kvalheim, Gunnar; Nesland, Jahn M; Suo, Zhenhe

    2013-01-01

    Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog. Moreover, sex hormone binding globulin (SHBG) was also simultaneously upregulated in these cells. When the SHBG gene was blocked by SHBG siRNA knock-down, the induction of Oct3/4, Nanog, CD44 and CD90 by DHT was also correspondingly blocked in these cells. Immunohistochemical evaluation of clinical samples disclosed weakly positive, and areas negative for SHBG expression in the benign prostate tissues, while most of the prostate carcinomas were strongly positive for SHBG. In addition, higher levels of SHBG expression were significantly associated with higher Gleason score, more seminal vesicle invasions and lymph node metastases. Collectively, our results show a role of SHBG in upregulating stemness of prostate cancer cells upon DHT exposure in vitro, and SHBG expression in prostate cancer samples is significantly associated with poor clinicopathological features, indicating a role of SHBG in prostate cancer progression.

  9. SHBG is an important factor in stemness induction of cells by DHT in vitro and associated with poor clinical features of prostate carcinomas.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Ma

    Full Text Available Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog. Moreover, sex hormone binding globulin (SHBG was also simultaneously upregulated in these cells. When the SHBG gene was blocked by SHBG siRNA knock-down, the induction of Oct3/4, Nanog, CD44 and CD90 by DHT was also correspondingly blocked in these cells. Immunohistochemical evaluation of clinical samples disclosed weakly positive, and areas negative for SHBG expression in the benign prostate tissues, while most of the prostate carcinomas were strongly positive for SHBG. In addition, higher levels of SHBG expression were significantly associated with higher Gleason score, more seminal vesicle invasions and lymph node metastases. Collectively, our results show a role of SHBG in upregulating stemness of prostate cancer cells upon DHT exposure in vitro, and SHBG expression in prostate cancer samples is significantly associated with poor clinicopathological features, indicating a role of SHBG in prostate cancer progression.

  10. SHBG Is an Important Factor in Stemness Induction of Cells by DHT In Vitro and Associated with Poor Clinical Features of Prostate Carcinomas

    Science.gov (United States)

    Ma, Yuanyuan; Liang, Dongming; Liu, Jian; Wen, Jian-Guo; Servoll, Einar; Waaler, Gudmund; Sæter, Thorstein; Axcrona, Karol; Vlatkovic, Ljiljana; Axcrona, Ulrika; Paus, Elisabeth; Yang, Yue; Zhang, Zhiqian; Kvalheim, Gunnar; Nesland, Jahn M.; Suo, Zhenhe

    2013-01-01

    Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog. Moreover, sex hormone binding globulin (SHBG) was also simultaneously upregulated in these cells. When the SHBG gene was blocked by SHBG siRNA knock-down, the induction of Oct3/4, Nanog, CD44 and CD90 by DHT was also correspondingly blocked in these cells. Immunohistochemical evaluation of clinical samples disclosed weakly positive, and areas negative for SHBG expression in the benign prostate tissues, while most of the prostate carcinomas were strongly positive for SHBG. In addition, higher levels of SHBG expression were significantly associated with higher Gleason score, more seminal vesicle invasions and lymph node metastases. Collectively, our results show a role of SHBG in upregulating stemness of prostate cancer cells upon DHT exposure in vitro, and SHBG expression in prostate cancer samples is significantly associated with poor clinicopathological features, indicating a role of SHBG in prostate cancer progression. PMID:23936228

  11. Evaluación de la globulina transportadora de hormonas esteroidales (SHBG) durante el embarazo como factor predictor de pre-eclampsia y restricción del crecimiento intrauterino

    OpenAIRE

    Valdés R,Enrique; Lattes A,Karina; Muñoz S,Hernán; Ángel Cumsille,Miguel

    2012-01-01

    Background: Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). Aim: To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Patients and Methods: Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselectedpregnant wome...

  12. 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

  13. Cortisol-binding globulin and meat quality in five European lines of pigs

    NARCIS (Netherlands)

    Geverink, N.A.; Foury, A.; Plastow, G.S.; Gil, L.; Gispert, M.; Hortós, M.; Font I Furnols, M.; Gort, G.; Moisan, M.P.; Mormède, P.

    2006-01-01

    The gene (Cbg) encoding cortisol-binding globulin (CBG) has been proposed as a candidate gene to explain genetic variation in cortisol secretion and carcass composition in pigs. The objective of this study was to evaluate the association between CBG and pork quality in 5 European breeding lines,

  14. Is the sex hormone binding globulin related to preeclampsia independent of insulin resistance

    International Nuclear Information System (INIS)

    Rahmanian, M.; Salari, Z.; Mirmohammadkhani, M.; Ghorbani, R.

    2014-01-01

    Objective: To evaluate the association between Sex Hormone Binding Globulin and preeclampsia in Iranian women considering the probable confounding effect of insulin resistance. Methods: The case-control study was conducted at the Semnan University of Medical Sciences, Iran, and comprised pregnant women who received prenatal care at Amiralmomenin Hospital in 2011. Cases represented patients admitted because of preeclampsia, while controls were randomly selected eligible pregnant women without hypertension and/or proteinuria. Fasting blood sugar and insulin were assessed for all participants as well as their blood concentration of Sex Hormone Binding Globulin. The Homeostasis Model Assessment of Insulin Resistance Score was used. The correlation between dependant and independent variables was reported by crude and adjusted odds ratio applying logistic regression models. SPSS 16.0 was used for statistical analysis. Results: Of the 100 pregnant women in the study, 45(45%) were cases. Insulin resistance was found to be significantly more frequent in the cases compared to the controls (adjusted odds ratio=2.78; 95% Confidence Interval: 1.11, 6.90; p<0.01). There was a significant reverse correlation between level of Sex Hormone Binding Globulin in blood and being a case of preeclampsia (adjusted odds ratio=0.99; 95% Confidence Interval: 0.98, 1.00; p=0.04). Conclusion: Independent of insulin resistance, every 1nmol/l increase in Sex Hormone Binding Globulin, decreases the odds of preeclampsia by 1%, notifying Sex Hormone Binding Globulin as an important biomarker about its etiology and prediction. (author)

  15. Thyroxine binding to serum thyronine-binding globulin in thyroidectomized adult and normal neonatal rats

    International Nuclear Information System (INIS)

    Young, R.A.; Meyers, B.; Alex, S.; Fang, S.L.; Braverman, L.E.

    1988-01-01

    The amount of tracer [125I]T4 bound to serum thyronine-binding globulin (TBG) was measured by polyacrylamide gel electrophoresis in adult thyroidectomized (TX) rats and normal 1-day to 4-week-old rat puts. Thyroidectomy was associated with the appearance of significant amounts of [125I]T4 binding to serum TBG in lean rats, but not in obese Zucker rats. Treatment of the TX rats in vivo with replacement doses of T4 prevented this increase in TBG binding, but enrichment of serum from TX rats with T4 did not. Significant amounts of tracer [125I]T4 binding to TBG was present in serum from 1- to 3-week-old normal rat pups, but not in 1-day- or 4-week-old pups. There were significantly higher levels of TBG binding of [125I]T4 in serum from 2-week-old rat pups raised in litters of 16 pups compared to those raised in litters of 4 pups. All manipulations that result in the appearance of TBG in rat serum also result in either weight loss or a slowing in the rate of growth, suggesting that the appearance of TBG in rat serum has a nutritional component. This possibility is further supported by the observations that increases in TBG binding of [125I]T4 are not found in obese Zucker rats fed a low protein-high carbohydrate diet for 14 days or fasted for 7 days, or after thyroidectomy, perhaps owing to the large stores of fuel in the obese rat

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. Isolation, characterization and radioimmunoassay of corticosteroid-binding globulin (CBG) in human serum - clinical significance and comparison to thyroxine-binding globulin (TBG)

    International Nuclear Information System (INIS)

    Bernutz, C.; Haensle, W.O.; Horn, K.; Pickardt, C.R.; Scriba, P.C.; Fink, E.; Kolb, H.; Tschesche, H.

    1979-01-01

    Isolation of the corticosteroid-binding globulin CBG was achieved by 5 chromatographical steps on cortisol Sepharose, QAE-Sephadex A-50, Con A-Sepharose and hydroxylapatite. The purity of the isolated CBG was demonstrated in polyacrylamide gel electrophoresis, SDS electrophoresis, immunodiffusion and ultracentrifugation. Microheterogeneity was shown in isoeletric focusing by 5 bands in the pH range of 3.7-4.2, which could be reduced to one major band after neuraminidase treatment. The equimolar binding of cortisol to CBG was demonstrated by binding studies. The association constant for cortisol was 2.8 x 10 8 M -1 , for progesterone 1.7 x 10 6 M -1 . From analytical ultracentrifugation, the molecular weight was calculated on 50 700; the sedimentation coefficient was 3.6 S, the partial specific volume 0.690 ml/g, the Stokes radius 38 A and the frictional coefficient ratio 1.5. A specific radioimmunoassay for CBG was established using the purified CBG for immunization, radioiodination and for calibration standards. The normal range of CBG levels in human serum was 2.4-4.4 mg/100 ml (mean +- 2SD). Studies were performed to compare the levels of CBG and thyroxine-binding globulin (TBG). No sex differences but a significant biphasic age dependence were observed for both proteins. In pregnancy and under oestrogen treatment of women and men, CBG was demonstrated to be the more distinct indicator of oestrogenic activity as compared with TBG, whereas the sensitivity of TBG was more pronounced to supposedly antioestrogenic substances like Danazol, and in severe disease. No coincidence of genetic CBG and TBG deficiencies have been found so far. (author)

  19. [Partial thyroxine binding globulin deficiency in test tube infants: report of cases and literature review].

    Science.gov (United States)

    Fang, Y L; Wang, C L; Liang, L

    2016-06-02

    To investigate the clinical characteristics of twins with thyroxine binding globulin (TBG) deficiency and to find SERPINA7 gene mutations. Data(2015) related to clinical characteristics, serum biochemistry, gene mutations and pedigree of two children with TBG deficiency were collected in the First Affiliated Hospital of College of Medicine, Zhejiang University. The related literature was searched form China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center for Biotechnology Information and PubMed (up to December 2015) by using search terms "Thyroxine binding globulin deficiency, gene, mutation" . Both patients were diagnosed as central hypothyroidism at the beginning and treated with L-thyroxine. Both of the identical twins of the triplet were observed for mutation in exon3, c. 631G﹥A(p.A211T), a new mutation had not been reported, but their parents and another non-identical triplet brother were normal. Literature review showed that 23 foreign cases with SERPINA7 gene mutation had been reported, however, no Chinese with SERPINA7 gene mutation had been reported. Among reported cases it was shown that SERPINA7 gene mutations located in exon, intron, promoter and enhancer. Up to now, 49 variants had been identified, 41 of them located in the mutated genes. Including these two cases, patients with thyroxine binding globulin deficiency were characterized by reduced serum TH levels, but normal free TH and TSH and absence of clinical manifestations. The new mutation of SERPINA7 gene c. 631G﹥A(p.A211T)is not transmitted via the known X chromosome linked heredity, and as the cases were test tube triplet infants, it is a de novo mutation. The serum thyroid function tests of TBG deficiency showed decreased TT4, TT3 and normal TSH and TBG deficiency is often misdiagnosed as central hypothyroidism.

  20. Fasting induces the generation of serum thyronine-binding globulin in Zucker rats

    International Nuclear Information System (INIS)

    Young, R.A.; Rajatanavin, R.; Moring, A.F.; Braverman, L.E.

    1985-01-01

    Five-month-old lean and obese Zucker rats were fasted for up to 7 days (lean rats) or 28 days (obese rats), and serum total and free T4 and T3 concentrations, percent free T4 and T3 by equilibrium dialysis, and the binding of [ 125 I] T4 to serum proteins by gel electrophoresis were measured. In the lean rats, a 4- or 7-day fast resulted in significant decreases in serum total and free T4 and T3 concentrations. There was a decrease in the percent free T3 after 7 days of starvation. In contrast, a 4- or 7-day fast did not alter any of these variables in the obese rats. However, after 14 or more days of starvation, serum total T4 and T3 concentrations increased, and the percent free T4 and T3 decreased, resulting in no change in the serum free T4 or T3 concentrations in the obese rats. The percent of [ 125 I]T4 bound to serum thyronine-binding globulin increased and the percent bound to thyronine-binding prealbumin decreased with the duration of the fast in both the lean and obese rats. The increase in serum thyronine-binding globulin binding of T4 can explain the increase in serum total T4 and T3 concentrations, the decrease in percent free T4 and T3, and the normal free hormone concentration in the long term fasted obese rats. The findings in the lean rats appear to be due to a combination of the known central hypothyroidism that occurs during 4-7 days of fasting and the fasting-induced changes in T4 binding in serum. Changes in T4 and T3 binding in serum during fasting in the rat must be considered when the effects of fasting on serum concentrations of the thyroid hormones, thyroid hormone kinetics, and the peripheral action of the thyroid hormones are evaluated

  1. 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

  2. Comparative characterization of molecular varieties of thyroxine-binding human globulin

    International Nuclear Information System (INIS)

    Ermolenko, M.N.; Sviridov, O.V.; Strel'chenok, O.A.

    1986-01-01

    Two molecular varieties of thyroxine-binding globulin (TBG) of human retroplacental blood, obtained as a result of fractionation of pure TBG on concanavalin A-Sepharose, were studied. It was shown that these varieties (TBG-1 and TBG-2) are immunologically identical; they have the same molecular weight and amino acid composition, exhibit the same affinity for thyroid hormones, and are indistinguishable in spectral characteristics. And yet, TBG-1 and TBG-2 have differences in charge, detectable in isoelectrofocusing, and a different monosaccharide composition. The existence of molecular varieties of TBG during pregnancy is apparently due to the peculiarities of the glycosylation of the polypeptide chain during TBG biosynthesis

  3. Radioimmunoassay of testosterone and of sexual hormone-binding globulin in plasma of women with hirsutism

    International Nuclear Information System (INIS)

    Warenik-Szymankiewicz, A.; Baron, J.; Chawlisz, K.

    1980-01-01

    Plasma-borne testosterone was determined in 176 women with hirsutism, and in 47 patients sexual hormone-binding globulin was determined as well. The highest average testosterone values were recorded from cases with congenital adrenogenital syndrome (AGS). In cases of postnatal AGS values were much lower, but they were clearly in excess of those recordable from Stein-Leventhal syndrome. Plasma borne testosterone in cases of hirsutism came very close to testosterone levels established in the context of Stein-Leventhal syndrome. Testosterone levels dropped with significance, following AGS treatment, using cortisol derivatives, and following wedge-shaped ovariectomy. Sexual hormone binding-globulin was found to be strongly reduced in almost all women with hirsutism. Such reduction seemed to suggest the presence of increased amounts of free active testosterone in the blood of those patients. Determination of plasma-borne testosterone in cases of hirsutism is considered to be essential to both diagnosis of the endocrinological syndromes and monitoring of therapy. (author)

  4. Sex steroid hormones and sex hormone binding globulin levels, CYP17 MSP AI (-34T:C) and CYP19 codon 39 (Trp:Arg) variants in children with developmental stuttering.

    Science.gov (United States)

    Mohammadi, Hiwa; Joghataei, Mohammad Taghi; Rahimi, Zohreh; Faghihi, Faezeh; Khazaie, Habibolah; Farhangdoost, Hashem; Mehrpour, Masoud

    2017-12-01

    Developmental stuttering is known to be a sexually dimorphic and male-biased speech motor control disorder. In the present case-control study, we investigated the relationship between developmental stuttering and steroid hormones. Serum levels of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), oestradiol, progesterone, cortisol, and sex hormone binding globulin (SHBG), as well as the 2nd/4th digit ratio (2D:4D), an indicator of prenatal testosterone level, were compared between children who stutter (CWS) and children who do not stutter (CWNS). Moreover, two SNPs (CYP17 -34 T:C (MSP AI) and CYP19 T:C (Trp:Arg)) of cytochrome P450, which is involved in steroid metabolism pathways, were analysed between the groups. Our results showed significantly higher levels of testosterone, DHT, and oestradiol in CWS in comparison with CWNS. The severity of stuttering was positively correlated with the serum levels of testosterone, DHEA, and cortisol, whereas no association was seen between the stuttering and digit ratio, progesterone, or SHBG. The CYP17CC genotype was significantly associated with the disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The relationship between pubertal gynecomastia, prostate specific antigen, free androgen index, SHBG and sex steroids.

    Science.gov (United States)

    Kilic, Mustafa; Kanbur, Nuray; Derman, Orhan; Akgül, Sinem; Kutluk, Tezer

    2011-01-01

    To investigate the relationships between pubertal gynecomastia, prostate-specific antigen (PSA), free androgen index (FAI), sex hormone-binding globulin (SHBG) and sex steroids. A total of 61 male adolescents (10-17 years old; mean: 13.67 +/- 1.08) with gynecomastia were enrolled into the study group. A total of 65 healthy age-matched adolescents were included in the control group. Body mass index (BMI), Tanner staging, testis volume, stretched penis length (SPL) and bone age were evaluated. Serum follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E2), testosterone, free testosterone, SHBG, PSA levels were determined and FAI was calculated. In the study group, free testosterone (p = 0.012) and FAI (p = 0.05) were significantly lower than the control group. In the control group, SHBG levels decreased (p 0.05). High FAI was found to decrease the risk of gynecomastia (odds ratio: 0.211, 95% confidence interval: 0.064-0.694, p = 0.01). PSA showed a positive correlation with FAI, free testosterone, Tanner staging, testosterone, E2 and LH levels. PSA is a good indicator of androgen activity during puberty. However, owing to FAI remaining as the single significant variable for pubertal gynecomastia, we suggest that it is still the best parameter to elucidate the etiopathogenesis of gynecomastia as well as other pubertal developmental abnormalities in male adolescents, and further longitudinal studies are needed to investigate the relationships between PSA and FAI in puberty.

  6. In vitro thyroid testing in populations with low thyroxine binding globulin capacity

    Energy Technology Data Exchange (ETDEWEB)

    Cuaron, A

    1993-12-31

    Total thyroxine (T{sub 4}) concentration in serum is a reliable indicator of thyroid function in most individuals, but it is affected by altered concentrations of thyroxine-binding globulin (TBG) in serum. Within certain limits, the variations in total TBG binding capacity (TBG{sub TOTAL}) caused by the fluctuations in the concentration of this binding globulin in serum can be modulated by calculating the free thyroxine index (FT{sub 4}I) as the product of T{sub 4} and the in vitro uptake of triiodothyronine by a secondary binder (T{sub 3}U). This calculation is empirically based on the facts that free TBG binding capacity (TBG{sub FREE}) is inversely related to T{sub 3}U and that T{sub 4} and T{sub 3}U show opposite behaviour when measured in sera with altered TBG: a low T{sub 4} in serum with reduced TBG{sub TOTAL} is compensated by a high value for T{sub 3}U, while an elevated T{sub 4} in serum with increased TBG{sub TOTAL} is compensated by a low value for T{sub 3}U. In both cases the product of T{sub 4} and T{sub 3} renders a normal FT{sub 4}I value, showing a certain association with the concentration of free T{sub 4} in serum (FT{sub 4}). In fact, this index has been shown to be superior than several FT{sub 4} assay systems in the assessment of thyroid status in clinical euthyroid subjects with relatively high or low T{sub 3}U 3 figs, 4 tabs

  7. Intraindividual variation of triiodothyronine, thyroxine, thyrotropin and thyroxine-binding globulin in fasting serum from healthy men

    International Nuclear Information System (INIS)

    Liappis, N.; Hoffmann, U.; Rao, M.L.

    1986-01-01

    The concentrations of triiodothyronine, thyroxine, thyrotropin and thyroxine-binding globulin were determined in fasting serum from 11 healthy men (age 18-25 years) by radioimmunoassays conducted over a period of 4 weeks on 5 consecutive days per week. The concentrations of thyroxine and thyroxine-binding globulin were very consistent intraindividually, with coefficients of variation of 7.84% and 9.37%, respectively. The triiodothyronine and thyrotropin levels showed significant intraindividual variability with coefficients of variation of 18.38% and 51.85%, respectively. These results point to the type of difficulties encountered in judging serum values, namely intraindividual variations over a given period of time. (orig.) [de

  8. The contribution of SHBG to the variation in HOMA-IR is not dependent on endogenous oestrogen or androgen levels in postmenopausal women.

    Science.gov (United States)

    Davis, Susan R; Robinson, Penelope J; Moufarege, Alain; Bell, Robin J

    2012-10-01

    Sex hormone-binding globulin (SHBG) is a robust predictor of insulin resistance. Whether this is independent of circulating sex steroid levels remains uncertain. The aim of this study was to investigate the determinants of SHBG in postmenopausal women and whether the relationship between SHBG and insulin resistance is independent of oestrogen and androgen levels. A cross-sectional study of naturally and surgically menopausal women. Seven hundred and sixty three postmenopausal women not using any systemic hormone therapy, mean age 54·4 ± 5·8 years, recruited in the US, Canada, Australia, UK and Sweden between July 2004 and February 2005. Relationships between log-transformed (ln) SHBG and ln homoeostasis model assessment for insulin resistance (HOMA-IR) were explored, taking into account age, body mass index (BMI), blood pressure (BP) and circulating oestradiol, oestrone, testosterone and dihydrotestosterone. Taking into account age, race, years since menopause, menopause type, BMI, BP, prior postmenopausal hormone use and the sex steroids measured, 34·4% of the variation in SHBG could be explained by the model that included negative contributions by HOMA-IR, BMI and diastolic BP, and a positive contribution by total testosterone (P HOMA-IR, which was best explained by the model that included BMI, SHBG, systolic BP and surgical menopause, with each variable being positively related to HOMA-IR (r(2) = 0·3152, P = 0·03). The relationship between SHBG and HOMA-IR, as an estimate of insulin resistance, is not explained by endogenous oestrogen and androgen levels and is, at least in part, independent of BMI in postmenopausal women. © 2011 Blackwell Publishing Ltd.

  9. Control survey of normal reference ranges adopted for serum thyroxine binding globulin, thyroxine, triiodothyronine in Japan

    International Nuclear Information System (INIS)

    Sugisaki, Hajime; Kameyama, Mayumi; Shibata, Kyoko

    1985-01-01

    A survey using questionnaires was made on 152 facilities from July through September 1984 to examine normal reference ranges of serum thyroxine binding globulin (TBG), thyroxine (TT 4 ), and triiodothyronine (TT 3 ). Normal reference ranges of TBG were in good agreement with each other, with the exception of four facilities showing high upper limits. An average value of the upper and lower limits in 83 facilities was 13.7 +- 1.9 μg/ml; and the standard deviation was 28.6 +- 2.8 μg/ml. Differences (approximately 10 %) in coefficient of variation were comparable to those (5.7-9.6 %) obtained from the previous survey. There were approximately 10 % differences in coefficient of variation for both TT 4 and TT 3 . (Namekawa, K.)

  10. Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin.

    Science.gov (United States)

    Sheikh, Ishfaq A; Beg, Mohd A

    2017-12-01

    Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Measurement of free glucocorticoids: quantifying corticosteroid-binding globulin binding affinity and its variation within and among mammalian species.

    Science.gov (United States)

    Delehanty, Brendan; Hossain, Sabrina; Jen, Chao Ching; Crawshaw, Graham J; Boonstra, Rudy

    2015-01-01

    Plasma glucocorticoids (GCs) are commonly used as measures of stress in wildlife. A great deal of evidence indicates that only free GC (GC not bound by the specific binding protein, corticosteroid-binding globulin, CBG) leaves the circulation and exerts biological effects on GC-sensitive tissues. Free hormone concentrations are difficult to measure directly, so researchers estimate free GC using two measures: the binding affinity and the binding capacity in plasma. We provide an inexpensive saturation binding method for calculating the binding affinity (equilibrium dissociation constant, K d) of CBG that can be run without specialized laboratory equipment. Given that other plasma proteins, such as albumin, also bind GCs, the method compensates for this non-specific binding. Separation of bound GC from free GC was achieved with dextran-coated charcoal. The method provides repeatable estimates (12% coefficient of variation in the red squirrel, Tamiasciurus hudsonicus), and there is little evidence of inter-individual variation in K d (range 2.0-7.3 nM for 16 Richardson's ground squirrels, Urocitellus richardsonii). The K d values of 28 mammalian species we assessed were mostly clustered around a median of 4 nM, but five species had values between 13 and 61 nM. This pattern may be distinct from birds, for which published values are more tightly distributed (1.5-5.1 nM). The charcoal separation method provides a reliable and robust method for measuring the K d in a wide range of species. It uses basic laboratory equipment to provide rapid results at very low cost. Given the importance of CBG in regulating the biological activity of GCs, this method is a useful tool for physiological ecologists.

  12. Serum corticosteroid binding globulin expression is modulated by fasting in polar bears (Ursus maritimus).

    Science.gov (United States)

    Chow, Brian A; Hamilton, Jason; Cattet, Marc R L; Stenhouse, Gordon; Obbard, Martyn E; Vijayan, Mathilakath M

    2011-01-01

    Polar bears (Ursus maritimus) from several subpopulations undergo extended fasting during the ice-free season. However, the animals appear to conserve protein despite the prolonged fasting, though the mechanisms involved are poorly understood. We hypothesized that elevated concentrations of corticosteroid binding globulin (CBG), the primary cortisol binding protein in circulation, lead to cortisol resistance and provide a mechanism for protein conservation during extended fasting. The metabolic state (feeding vs. fasting) of 16 field sampled male polar bears was determined based on their serum urea to creatinine ratio (>25 for feeding vs. polar bears sampled. Serum CBG expression was greater in lactating females relative to non-lactating females and males. CBG expression was significantly higher in fasting males when compared to non-fasting males. This leads us to suggest that CBG expression may serve as a mechanism to conserve protein during extended fasting in polar bears by reducing systemic free cortisol concentrations. This was further supported by a lower serum glucose concentration in the fasting bears. As well, a lack of an enhanced adrenocortical response to acute capture stress supports our hypothesis that chronic hunger is not a stressor in this species. Overall, our results suggest that elevated serum CBG expression may be an important adaptation to spare proteins by limiting cortisol bioavailability during extended fasting in polar bears. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Clinical evaluation of thyroxine-binding globulin (TBG) as a marker of liver tumors

    Energy Technology Data Exchange (ETDEWEB)

    Terui, S

    1984-03-01

    This investigation was undertaken to evaluate thyroxine-binding globulin (TGB) as a marker of liver tumors, in conjection with the liver scintigram. Of 30 patients with primary hepatocellular carcinoma (PHC), 22 (73.3%) showed significantly higher TBG concentrations. Eight patients (26.7%) showed normal TBG concentrations. In the case of 27 our of 30 patients with definite liver tumors, defects were apparent on the scintigrams. But seven of them had normal TBG concentrations in spite of the defects on the scintigrams. Out of 33 postoperative patients with liver metastasis, 28 (84%) had a raised TBG concentration. Only five (15.2%) had a normal TBG level. In 31 patients (93.9%) out of 33 with liver metastasis, a definite diagnosis was made on the basis of the liver scintigram. In 28 (90.3%) of these 31 people, the TBG concentration was higher than normal. Among 63 patients with liver tumors, both primary and metastatic, the test sensitivity for liver tumors was 92.1% (58/63) based on the accuracy of the liver scintigram. It was 79.4% (50/63) based on the TBG measurement. Why TBG increases to such an extent in spite of the euthyroid state remains unexplained. But it may be concluded that elevated TBG with positive liver scintigram furnishes a sensitive, fairly reliable, nonspecific tumor marker to determine liver tumors, especially in the case of liver metastasis.

  14. Serum Thyroxine to Thyroxine-Binding Globulin Ratio in Pregnancy and Newborn

    International Nuclear Information System (INIS)

    Kim, Ji Yeul

    1982-01-01

    To evaluate the diagnostic value of the ratio of serum thyroxine(T 4 ) /thyroxine-binding globulin (TBG) for the thyroid status in pregnancy and newborn serum thyroxine, TBG, triiodothyronine, and free thyroxine levels were radioimmunoassayed in normal pregnant women at each of the trimesters, and the calculated serum T 4 /TBG ratios were compared with other parameters such as T 3 /TBG ratio and free T 4 /TBG ratio and free T 4 /TBG ratio. Serum T 4 levels were elevated with the proportionate increase in TBG levels during pregnancy, leading to the nearly constant value of serum T 4 /TBG ratios as in normal non-pregnant controls. In contrast, serum T 3 /TBG and free T 4 /TBG ratios varied considerably during pregnancy. In newborn, T 4 levels were nearly not changed with compared non-pregnant control value and TBG levels were elevated. The results indicate that serum T 4 /TBG ratio is a better parameter than others in evaluating the thyroid status during pregnancy and but newborn is a no better.

  15. Spatial and temporal dynamics of corticosterone and corticosterone binding globulin are driven by environmental heterogeneity.

    Science.gov (United States)

    Shultz, Michael Todd; Kitaysky, Alexander Stanislav

    2008-02-01

    The question of whether changes in glucocorticoid concentrations reflect consistent changes in physiology associated with transitions between different stages of reproduction, or whether they reflect responses to environmental conditions, is one the central issues in field endocrinology studies. We examined the temporal and spatial dynamics of corticosterone (CORT, baseline, and acute stress-induced) and corticosterone binding globulin (CBG) concentrations in blood of Black-legged Kittiwakes (Rissa tridactyla) breeding at four major colonies in the Bering Sea, Alaska, during 1999-2005. We found that total CORT, free CORT, and CBG capacity varied inconsistently among reproductive stages, colonies, and years. Total CORT levels were positively correlated with CBG capacity. Variation in free CORT was largely driven by variation in total CORT. Results suggest that the adrenocortical function and CBG in breeding kittiwakes do not vary as a consequence of stage-specific modulation associated with a particular reproductive stage as in some short-lived passerine birds. Rather, in accord with predictions for a long-lived species, the lack of consistent colony, year, and reproductive stage patterns in baseline and maximum CORT, and CBG indicates that environmental factors, probably local dynamics of food availability, drive variation in these factors.

  16. Clinical evaluation of thyroxine-binding globulin (TBG) as a marker of liver tumors

    International Nuclear Information System (INIS)

    Terui, S.

    1984-01-01

    This investigation was undertaken to evaluate thyroxine-binding globulin (TGB) as a marker of liver tumors, in conjection with the liver scintigram. Of 30 patients with primary hepatocellular carcinoma (PHC), 22 (73.3%) showed significantly higher TBG concentrations. Eight patients (26.7%) showed normal TBG concentrations. In the case of 27 our of 30 patients with definite liver tumors, defects were apparent on the scintigrams. But seven of them had normal TBG concentrations in spite of the defects on the scintigrams. Out of 33 postoperative patients with liver metastasis, 28 (84%) had a raised TBG concentration. Only five (15.2%) had a normal TBG level. In 31 patients (93.9%) out of 33 with liver metastasis, a definite diagnosis was made on the basis of the liver scintigram. In 28 (90.3%) of these 31 people, the TBG concentration was higher than normal. Among 63 patients with liver tumors, both primary and metastatic, the test sensitivity for liver tumors was 92.1% (58/63) based on the accuracy of the liver scintigram. It was 79.4% (50/63) based on the TBG measurement. Why TBG increases to such an extent in spite of the euthyroid state remains unexplained. But it may be concluded that elevated TBG with positive liver scintigram furnishes a sensitive, fairly reliable, nonspecific tumor marker to determine liver tumors, especially in the case of liver metastasis. (orig.)

  17. Sex hormone binding globulin and sex steroids among premenopausal women in the diabetes prevention program.

    Science.gov (United States)

    Kim, Catherine; Pi-Sunyer, Xavier; Barrett-Connor, Elizabeth; Stentz, Frankie B; Murphy, Mary Beth; Kong, Shengchun; Nan, Bin; Kitabchi, Abbas E

    2013-07-01

    It is unknown whether intensive lifestyle modification (ILS) or metformin changes sex steroids among premenopausal women without a history of polycystic ovarian syndrome (PCOS). We examined 1-year intervention impact on sex steroids (estradiol, testosterone, dehydroepiandrosterone, and androstenedione [A4]) and SHBG and differences by race/ethnicity. A subgroup of Diabetes Prevention Program participants who were premenopausal, not using estrogen, without a history of PCOS or irregular menses, and who reported non-Hispanic white (NHW), Hispanic, or African-American race/ethnicity (n = 301). Randomization arms were 1) ILS with the goals of weight reduction of 7% of initial weight and 150 minutes per week of moderate intensity exercise, 2) metformin 850 mg twice a day, or 3) placebo. Neither intervention changed sex steroids compared to placebo. ILS, but not metformin, increased median SHBG by 3.1 nmol/L (~11%) compared to decreases of 1.1 nmol/L in the placebo arm (P < .05). This comparison remained significant after adjustment for changes in covariates including waist circumference. However, associations with glucose were not significant. Median baseline A4 was lower in Hispanics compared to NHWs (5.7 nmol/L vs 6.5 nmol/L, P < .05) and increases in A4 were greater in Hispanics compared to NHWs (3.0 nmol/ vs 1.2 nmol/L, P < .05), and these differences did not differ significantly by intervention arm. No other racial/ethnic differences were significant. Among premenopausal glucose-intolerant women, no intervention changed sex steroids. ILS increased SHBG, although associations with glucose were not significant. SHBG and sex steroids were similar by race/ethnicity, with the possible exception of lower baseline A4 levels in Hispanics compared to NHWs.

  18. 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.

  19. Gene amplification as a cause of inherited thyroxine-binding globulin excess in two Japanese families

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Yuichi; Miura, Yoshitaka; Saito, Hidehiko [Toyota Memorial Hospital (Japan)] [and others

    1995-12-01

    T{sub 4}-binding globulin (TBG) is the major thyroid hormone transport protein in man. Inherited abnormalities in the level of serum TBG have been classified as partial deficiency, complete deficiency, and excess. Sequencing analysis of the TBG gene, located on Xq21-22, has uncovered the molecular defects causing partial and complete deficiency. However, the mechanism leading to inherited TBG excess remains unknown. In this study, two Japanese families, F-A and F-T, with inherited TBG excess were analyzed. Serum TBG levels in hemizygous males were 58 and 44 {mu}g/mL, 3- and 2-fold the normal value, respectively. The molecule had normal properties in terms of heat stability and isoelectric focussing pattern. The sequence of the coding region and the promoter activity of the TBG gene were also indistinguishable between hemizygotes and normal subjects. The gene dosage of TBG relative to that of {beta}-globin, which is located on chromosome 11, and Duchenne muscular dystropy, which is located on Xp, was evaluated by coamplification of these target genes using polymerase chain reaction and subsequent quantitation by HPLC. The TBG/{beta}-globin ratios of the affected male and female of F-A were 3.13 and 4.13 times, respectively, that in the normal males. The TBG/Duchenne muscular dystrophy ratios were 2.92 and 2.09 times the normal value, respectively. These results are compatible with three copies of TBG gene on the affected X-chromosome. Similarly, a 2-fold increase in gene dosage was demonstrated in the affected hemizygote of F-T. A 3-fold tandem amplification of the TBG gene was shown by in situ hybridization of prometaphase and interphase chromosomes from the affected male with a biotinylated genomic TBG probe, confirming the gene dosage results. Gene amplification of TBG is the cause of inherited TBG excess in these two families. 35 refs., 3 figs., 2 tabs.

  20. Circadian variation in serum cortisol during hydrocortisone replacement is not attributable to changes in cortisol-binding globulin concentrations.

    Science.gov (United States)

    Chung, T T; Gunganah, K; Monson, J P; Drake, W M

    2016-04-01

    Patients taking hydrocortisone (HC) replacement for primary or secondary adrenal failure require individual adjustment of their dose. In addition to modifying the administered doses of HC for each patient, physicians are increasingly interested in variations in the bioavailability of glucocorticoid replacement. One potential determinant of the bioavailability of replaced HC is a variation in serum cortisol-binding globulin (CBG) concentration, which may, in turn, affect interpretation of cortisol profiles and individual dose selection for patients on hydrocortisone replacement therapy. To investigate the hypothesis that there is a circadian variation in CBG levels. A total of 34 male patients divided into 3 groups (10 patients with non-somatotroph structural pituitary disease on HC replacement, 11 patients with treated acromegaly on HC replacement and 13 patients with treated acromegaly not on HC replacement) and 10 healthy volunteers were included. Cortisol and CBG levels were measured at 6 time points (0800, 1100, 1300, 1500, 1700 and 1900). No significant circadian variation in CBG concentration was found in any of the 4 groups. Circadian variation in serum cortisol during hydrocortisone replacement is not attributable to changes in cortisol-binding globulin concentration. Changes in serum cortisol levels may thus be explained by other factors including 11 β-hydroxysteroid dehydrogenase type 1 activity or circadian changes in the binding properties of CBG. © 2015 John Wiley & Sons Ltd.

  1. 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.

  2. Isoforms of thyroxine-binding globulin as a model for molecular epidemiology of human cancer risk

    International Nuclear Information System (INIS)

    Golovaty, A.S.; Lapko, A.G.

    2000-01-01

    The novel field of molecular epidemiology of human cancer risk has added a new branch to classical epidemiology by providing a direct link between human cancer and carcinogen exposure. It was estimated that about 80% of cancers are due to environmental factors. The blood proteins are almost certainly targets for modification in human cancer, and their identification and characterization will be of primary importance in the development of the new and rapidly evolving field of molecular epidemiology. Among blood proteins that are altered in human cancer, TBG occupies a special place because the level of human blood TBG is the most sensitive to intensification of biosynthesis and proliferation processes in organisms in different types of cancer. The increase of TBG concentration in cancer can be result from both activation of TBG biosynthesis in liver or altering of post translation glycosylation that prolongs protein survival time. The molecular basis for the change in the properties of TBG in cancer is unknown. These distinctive changes could have important consequences for the function of TBG in cancer and may help to develop more precise markers for monitoring pathological progression in this disease. Considerable variability and subtlety can occur in the carbohydrate composition and structure of serum glycoproteins in disease. This can be either as a major change, such as an increase in the number of oligosaccharide branches at a particular glycosylation site or as a minor change such as the addition of an extra fucose or sialic acid residue. Increased fucosylation has also been reported for transferrin and alpha-fetoprotein in liver cancer; thyroglobulin in thyroid cancer, IgG in myeloma, haptoglobin in ovarian cancer. The last own studies have shown that in clinically healthy teenagers born in Khojniki (137 Cs 185-555 kBq/m), we have found an unusual thyroid profile exhibiting increased levels of total triiodothyronine (T3), total thyroxine (T4), and thyroxine-binding

  3. The effect of extracts of the roots of the stinging nettle (Urtica dioica) on the interaction of SHBG with its receptor on human prostatic membranes.

    Science.gov (United States)

    Hryb, D J; Khan, M S; Romas, N A; Rosner, W

    1995-02-01

    Extracts from the roots of the stinging nettle (Urtica dioica) are used in the treatment of benign prostatic hyperplasia. The mechanisms underlying this treatment have not been elucidated. We set out to determine whether specific extracts from U. dioica had the ability to modulate the binding of sex hormone-binding globulin to its receptor on human prostatic membranes. Four substances contained in U. dioica were examined: an aqueous extract; an alcoholic extract; U. dioica agglutinin, and stigmasta-4-en-3-one. Of these, only the aqueous extract was active. It inhibited the binding of 125I-SHBG to its receptor. The inhibition was dose related, starting at about 0.6 mg/ml and completely inhibited binding at 10 mg/ml.

  4. Serum-sex steroids, gonadotrophins and sex hormone-binding globulin inprostatic hyperplasia

    International Nuclear Information System (INIS)

    Ansari, Mohammad A. Jalil; Begum, D.; Islam, F.

    2008-01-01

    Benign prostatic hyperplasia (BPH) develops in elderly males when serumandrogens are relatively lower than in healthy younger males, but is not wellunderstood whether and how sex steroids are altered in prostatic hyperplasia.It is also uncertain that whether there is any change in sex steroids levelsin males older than 40 years of age. The use of androgens in elderly males isoften discouraged because of the probable worsening effect of androgens onprostatism. This study aimed to determine the relationship between prostatichyperplasia and sex steroid levels and whether there is any significantchange in these hormones after the age of 40 years. We studied healthy malesof >40 years with (n=92) or without (n=93) clinical prostatic hyperplasia.Serum testosterone, estradiol, gonadotrophins and sex hormone-bindingglobulin (SHBG) were compared. The hormones and SHGB were also correlatedwith age. No significant difference was found in any hormone in cases withprostatic hyperplasia as compared with the controls. There was no significantage-related change in any hormone except estradiol where as a negativecorrelation (P<0.003) with age was found. Serum sex steroids and SHGBremained unchanged in symptomatic prostatic hyperplasia and except forestrdoil there was no significant age-related change in serum testosterone,gonadotrophins and SHGB in healthy males after the fourth decade. Morestudies are needed to confirm the age-related decline of estrogens in males.(author)

  5. Characteristics of chemical binding to alpha 2u-globulin in vitro--evaluating structure-activity relationships

    International Nuclear Information System (INIS)

    Borghoff, S.J.; Miller, A.B.; Bowen, J.P.; Swenberg, J.A.

    1991-01-01

    alpha 2u-Globulin (alpha 2u) has been shown to accumulate in the kidneys of male rats treated with 2,2,4-trimethylpentane (TMP). 2,4,4-Trimethyl-2-pentanol (TMP-2-OH), a metabolite of TMP, is found reversibly bound to alpha 2u isolated from the kidneys of these treated rats. The objectives of the following study were to characterize the ability of [3H]TMP-2-OH to bind to alpha 2u in vitro and to determine whether other compounds that cause this protein to accumulate have the same binding characteristics. Although compounds that have been shown to cause the accumulation of alpha 2u in male rat kidneys compete in vitro with [3H]TMP-2-OH for binding to alpha 2u, they do so to varying degrees. The binding affinity (Kd) of the [3H]TMP-2-OH-alpha 2u complex was calculated to be on the order of 10(-7) M. The inhibition constant values (Ki) determined for d-limonene, 1,4-dichlorobenzene, and 2,5-dichlorophenol were all in the range 10(-4) M, whereas the Ki values for isophorone, 2,4,4- or 2,2,4-trimethyl-1-pentanol, and d-limonene oxide were determined to be in the range 10(-6) and 10(-7) M, respectively. TMP and 2,4,4- and 2,2,4-trimethylpentanoic acid did not compete for binding. This suggests that other factors, besides binding, are involved in the accumulation of alpha 2u. In this study the ability of a chemical to bind to alpha 2u was used as a measure of biological activity to assess structure-activity relationships among the chemicals tested and known to cause the accumulation of alpha 2u. The results so far suggest that binding is dependent on both hydrophobic interactions and hydrogen bonding

  6. Reduction of the non-specific binding of DNA to gamma-globulin in Farr radioimmunoassay by addition of dextran sulfate and calcium chloride

    Energy Technology Data Exchange (ETDEWEB)

    Wakizaka, A; Okuhara, E [Akita Univ. (Japan)

    1979-01-23

    The effect of non-specific binding caused by the interaction between gamma-globulin and denatured DNA was markedly reduced by addition of dextran sulfate or CaCl/sub 2/ at alkaline pH. This method was shown to be applicable in the detection of anti-DNA antibodies in sera from cases of human systemic lupus erythematosus.

  7. Characterization and quantification of corticosteroid-binding globulin in a southern toad, Bufo terrestris, exposed to coal-combustion-waste

    Energy Technology Data Exchange (ETDEWEB)

    Ward, C.K.; Fontes, C.; Breuner, C.W.; Mendonca, M.T. [Auburn University, Auburn, AL (USA). Dept. of Biological Science

    2007-05-15

    Corticosteroid-binding globulin (CBG) is a plasma protein that binds corticosterone and may regulate access of hormone to tissues. The role of CBG during a stress response is not clear. In this study, southern toads, Bufo terrestris, were exposed to a chronic pollutant (coal-combustion-waste), to determine changes in CBG and free corticosterone levels. Since toads exposed to chronic pollutants in previous studies did not exhibit the predicted changes in metabolic rate and mass, but did experience a significant elevation in total corticosterone, we hypothesized that CBG would likewise increase and thus, mitigate the effects of a chronic (i.e. 2 months) pollutant stressor. To conduct this study, we first characterized the properties of CBG in southern toads. After characterization, we monitored the changes in CBG, total corticosterone, and free corticosterone in male toads that were exposed to either coal-combustion-waste or control conditions. CBG increased in all groups throughout the experiment. Total corticosterone, on the other hand, was only significantly elevated at four weeks of exposure to coal-combustion-waste. The increase in CBG did not parallel the increase in total corticosterone; as a result, free corticosterone levels were not buffered by CBG, but showed a peak at four weeks similar to total corticosterone. This finding indicates that, in this species, CBG may not provide a protective mechanism during long-term pollution exposure.

  8. Biological half-life and transfer of maternal corticosteroid-binding globulin to amniotic fluid in the rabbit

    International Nuclear Information System (INIS)

    Seralini, G.E.; Underhill, C.M.; Smith, C.L.; Nguyen, V.T.; Hammond, G.L.

    1989-01-01

    Rabbit corticosteroid-binding globulin (CBG) from the serum of pregnant and nonpregnant females differs in terms of charge microheterogeneity, and both forms were, therefore, radiolabeled and injected iv into 23- to 27-day pregnant rabbits (n = 6) to assess their biological half-lives and possible transfer to the fetal compartment. After an initially rapid distribution phase, the serum half-lives of both forms of [ 125 I]CBG were essentially identical (approximately 13 h) and did not vary at different gestational ages. There was also no difference in the transfer of either form of [ 125 I]CBG from maternal to fetal compartments in any of the animals studied. Moreover, [ 125 I]CBG showed no sign of degradation and retained its steroid-binding activity in fetal urine and amniotic fluid. Twenty-two hours after administration of [ 125 I]CBG to rabbits (n = 2) at 23 days gestation, its mean level in fetal urine (7 cpm/microliter) and amniotic fluid (2.5 cpm/microliter) was much higher than that in fetal blood (0.6 cpm/microliter). More importantly, the specific activities of [ 125 I]CBG in fetal urine and amniotic fluid were comparable to that in maternal serum, and approximately 2 orders of magnitude higher than that in fetal serum. Taken together, these results suggest that CBG in fetal urine and amniotic fluid is largely of maternal origin, and that maternal CBG crosses the fetal kidney preferentially

  9. Monoclonal antibodies to the reactive centre loop (RCL) of human corticosteroid-binding globulin (CBG) can protect against proteolytic cleavage.

    Science.gov (United States)

    Lewis, John G; Elder, Peter A

    2017-07-01

    Corticosteroid-binding globulin (CBG) binds most of the cortisol in circulation and is a non-functional member of the family of serine protease inhibitors (serpins) with an exposed elastase sensitive reactive centre loop (RCL). The RCL can be cleaved by human neutrophil elastase, released from activated neutrophils, and can also be cleaved at nearby site(s) by elastase released by Pseudomonas aeruginosa, and at two further sites, also within the RCL, by bovine chymotrypsin. Cleavage of the RCL results in a conformational change accompanied by a marked decrease in affinity for cortisol and hence its release at the site of proteolysis. These cleavages are irreversible and the similar half-lives of cleaved and intact CBG could mean that there may be some advantage in slowing the rate of CBG cleavage in acute inflammation thereby increasing the proportion of intact CBG in circulation. Here we show, for the first time, that pre-incubation of tethered human CBG with two monoclonal antibodies to the RCL of CBG protects against cleavage by all three enzymes. Furthermore, in plasma, pre-incubation with both RCL monoclonal antibodies delays neutrophil elastase cleavage of the RCL and one of these RCL monoclonal antibodies also delays bovine chymotrypsin cleavage of the RCL. These findings may provide a basis and rationale for the concept of the use of RCL antibodies as therapeutic agents to effectively increase the proportion of intact CBG in circulation which may be of benefit in acute inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. 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.

  11. Massive weight loss decreases corticosteroid-binding globulin levels and increases free cortisol in healthy obese patients: an adaptive phenomenon?

    Science.gov (United States)

    Manco, Melania; Fernández-Real, José M; Valera-Mora, Maria E; Déchaud, Henri; Nanni, Giuseppe; Tondolo, Vincenzo; Calvani, Menotti; Castagneto, Marco; Pugeat, Michel; Mingrone, Geltrude

    2007-06-01

    Obesity, insulin resistance, and weight loss have been associated with changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data relating to this association are available. In this study, we aim to investigate the effects of massive weight loss on cortisol suppressibility, cortisol-binding globulin (CBG), and free cortisol index (FCI) in formerly obese women. Ten glucose-normotolerant, fertile, obese women (BMI >40 kg/m2, aged 38.66 +/- 13.35 years) were studied before and 2 years after biliopancreatic diversion (BPD) when stable weight was achieved and were compared with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic-hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide deconvolution method. No difference was found in cortisol suppression after DEX-ST before or after weight loss. A decrease in ACTH was significantly greater in control subjects than in obese (P = 0.05) and postobese women (P obese subjects, an increase of free cortisol was associated with a simultaneous decrease in CBG levels, which might be an adaptive phenomenon relating to environmental changes. This topic, not addressed before, adds new insight into the complex mechanisms linking HPA activity to obesity.

  12. Measurement for serum thyroxine-binding globulin (TBG) and its clinical assessment in diagnosis of thyroid states

    International Nuclear Information System (INIS)

    Imamura, Rikiyo; Yoshimasa, Yasunao; Hamada, Satoshi

    1979-01-01

    Serum levels of thyroxine (T 4 )-binding globulin (TBG) were determined by a radioimmunoassay using cellulose-linked antibody to TBG. Values obtained in healthy young adults averaged 1.62 +- 0.25 (SD) mg/100 ml, and no significant difference was detected between males and females. The TBG levels remained within the normal limit in hyperthyroidism while they were significantly increased in hypothyroidism. Interestingly enough, TBG levels were significantly elevated in chronic thyroidities with no overt hypothyroidism. In normal pregnancy, TBG was increased slightly in the first trimester, and markedly in the second and third trimesters. In one case of congenital TBG deficiency, no immunoreactive TBG was detected. It was demonstrated, further, that an inverse relationship (r = -0.7593) existed between the TBG level and serum triiodothyronine uptake index, and that a direct relation (r = +0.6557) was present between the TBG level and T 4 in sera from normal subjects and pregnancy. Ratios of T 4 /TBG were markedly increased in hyperthyroidism, and decreased in hypothyroidism, showing no overlap with the normal subjects, whereas they were below the normal limit in half the cases in the second and third trimesters of pregnancy. The radioimmunoassay for TBG was useful in evaluating hypothyroid states, because it could differentiate the increase in T 4 associated with elevated TBG from hyperthyroidism. (author)

  13. Specific labeling of the thyroxine binding site in thyroxine-binding globulin: determination of the amino acid composition of a labeled peptide fragment isolated from a proteolytic digest of the derivatized protein.

    Science.gov (United States)

    Tabachnick, M; Perret, V

    1987-08-01

    [125I] Thyroxine has been covalently bound to the thyroxine binding site in thyroxine-binding globulin by reaction with the bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene. An average of 0.47 mol of [125I] thyroxine was incorporated per mol protein; nonspecific binding amounted to 8%. A labeled peptide fragment was isolated from a proteolytic digest of the derivatized protein by HPLC and its amino acid composition was determined. Comparison with the amino acid sequence of thyroxine-binding globulin indicated partial correspondence of the labeled peptide with two possible regions in the protein. These regions also coincide with part of the barrel structure present in the closely homologous protein, alpha 1-antitrypsin.

  14. Use of sodium salicylate as a blocking agent for cortisol-binding-globulin in a radioimmunoassay for cortisol on unextracted plasma

    Energy Technology Data Exchange (ETDEWEB)

    Kane, J W [Withington Hospital, Manchester (UK)

    1979-07-01

    This report describes investigations into the use of sodium salicylate as a cortisol-binding-globulin blocking agent and the subsequent development of a radioimmunoassay for cortisol on unextracted plasma. Cortisol antiserum was raised against a cortisol 3-0-(carboxy-methyl) oxime-bovine serum albumin conjugate. A /sup 125/I-labelled cortisol-tyrosine methyl ester conjugate was also prepared for use in the assay. The radioimmunoassay developed involved no pre-treatment or extraction of the samples before analysis and was extremely simple to perform. Comparison with another radioimmunoassay for cortisol and with the Mattingly fluorimetric assay gave good correlation.

  15. Use of sodium salicylate as a blocking agent for cortisol-binding-globulin in a radioimmunoassay for cortisol on unextracted plasma

    International Nuclear Information System (INIS)

    Kane, J.W.

    1979-01-01

    This report describes investigations into the use of sodium salicylate as a cortisol-binding-globulin blocking agent and the subsequent development of a radioimmunoassay for cortisol on unextracted plasma. Cortisol antiserum was raised against a cortisol 3-0-(carboxy-methyl) oxime-bovine serum albumin conjugate. A 125 I-labelled cortisol-tyrosine methyl ester conjugate was also prepared for use in the assay. The radioimmunoassay developed involved no pre-treatment or extraction of the samples before analysis and was extremely simple to perform. Comparison with another radioimmunoassay for cortisol and with the Mattingly fluorimetric assay gave good correlation. (author)

  16. Involvement of reversible binding to alpha 2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity.

    Science.gov (United States)

    Charbonneau, M; Strasser, J; Lock, E A; Turner, M J; Swenberg, J A

    1989-06-01

    Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors in male but not in female rats or in either sex of mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), a component of unleaded gasoline, increased protein droplet formation and cell proliferation in male but not in female rat kidneys. These protein droplets contained, alpha 2u-globulin, a male rat-specific low-molecular-weight protein and 2,4,4-trimethyl-2-pentanol, a metabolite of TMP that was reversibly bound to this protein. Studies were undertaken to determine if 1,4-DCB produced similar effects; 1,2-DCB was used for comparison since it did not produce renal carcinogenesis in male rats. Gel filtration chromatography of a 116,000g supernatant prepared from kidneys of 1,4-[14C]DCB-treated rats showed that radiolabel coeluted with alpha 2u-globulin as one sharp peak as opposed to a multipeak pattern observed for 1,2-[14C]DCB; the maximal quantity of radiolabel for 1,4-DCB was twice that for 1,2-DCB. Equilibrium dialysis of kidney cytosol in the presence or absence of sodium dodecyl sulfate demonstrated that the radiolabel was reversibly bound to alpha 2u-globulin; the amount for 1,4-[14C]DCB-treated rats was almost twice as much as that for 1,2-[14C]DCB-treated rats. 1,2-DCB was also shown to be covalently bound to renal alpha 2u-globulin, and covalently bound to liver and plasma high-molecular-weight proteins. 1,4-DCB and, to a minor extent, 2,5-dichlorophenol, the major metabolite of 1,4-DCB, were reversibly bound to renal alpha 2u-globulin from 1,4-DCB-treated rats. 1,4-DCB increased protein droplet formation in male but not in female rat kidneys, whereas equimolar doses of 1,2-DCB showed no effect in either sex. Renal cell proliferation, measured by [3H]thymidine incorporation into renal DNA, was increased after 1,4-DCB but not after 1,2-DCB treatment. Nephrotoxicity and biochemical alterations induced by

  17. Extracellular and intracellular steroid binding proteins

    International Nuclear Information System (INIS)

    Wagner, R.K.

    1978-01-01

    Steroid hormone binding proteins can be measured, after the removal of endogenous steroids, as specific complexes with radio-labelled hormones. In this study all the requirements for a quantitative determination of steroid hormone binding proteins are defined. For different methods, agargel electrophoresis, density gradient centrifugation, equilibrium dialysis and polyacrylamide electrophoresis have been evaluated. Agar electrophoresis at low temperature was found to be the simplest and most useful procedure. With this method the dissociation rates of high affinity complexes can be assessed and absolute binding protein concentrations can be determined. The dissociation rates of the oestradiol-oestrogen receptor complex and the R-5020-progestin receptor complex are low (1-2% per h run time.) In contrast, that of complexes between androgen receptor and dihydrotestosterone (17β-hydroxy-5α-androstan-3-one (DHT), progestin receptor and progesterone, corticosteroid binding globulin (CBG) and cortisol or progesterone and sex hormone binding globulin (SHBG) and DHT were hign (16-27% per h run time). Target tissue extracts (cytosols) contain, besides soluble tissue proteins, large amounts of plasma proteins. The extent of this plasma contamination can be determined by measuring the albumin concentration in cytosols by immunodiffusion. In cytosols of 4 different human target tissues the albumin content varied from 20-30% corresponding to an even higher whole plasma concentration. Steroid binding plasma proteins, such as CBG and SHBG are constituents of this containment. (author)

  18. 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

    -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...

  19. Basal Testosterone and Sex Hormone Binding Globulin Levels in the Prediction of Stimulation Parameters and Cycle Outcome in Cycling Patients Undergoing in Vitro Fertilization

    Directory of Open Access Journals (Sweden)

    Özlem Moraloğlu

    2010-12-01

    CONCLUSION: Basal serum T levels during IVF have a positive correlation with part of the stimulation parameters including number of oocytes retrieved and the number of oocytes transferred. However, neither T nor SHBG has any affect on fertilization or pregnancy rates.

  20. Elevation of corticosteroid-binding globulin in Obese strain (OS) chickens: possible implications for the disturbed immunoregulation and the development of spontaneous autoimmune thyroiditis

    International Nuclear Information System (INIS)

    Faessler, R.; Schauenstein, K.; Kroemer, G.; Schwarz, S.; Wick, G.

    1986-01-01

    Basal plasma levels of corticosterone and corticosteroid-binding globulin (CBG) have been investigated in Obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis (SAT). Corticosterone was determined radioimmunologically, and CBG by using a highly sensitive radioligand saturation assay. OS chickens displayed total corticosterone levels not different from healthy normal White Leghorn (NWL) chickens. CBG, however, was found to be twice as high in OS chickens as compared with their healthy counterparts, irrespective of sex or age. This quantitative difference in the CBG level is not compensated for by either altered affinity or specificity of the molecule. Furthermore, no differences were found in the response of OS and NWL lymphocytes to the suppressive effect of glucocorticoids in vitro. It was therefore assumed that OS animals are deficient in free, hormonally active corticosterone. An additional indication for such a diminished glucocorticoid tonus was that in vivo treatment of OS chickens with glucocorticoid hormones, thus increasing the free and active hormone fraction, normalizes the T cell hyperreactivity and significantly reduces thyroid infiltration. Possible pathophysiological implications of a diminished glucocorticoid tonus for spontaneous autoimmunity, as well as possible explanations for the beneficial effects of glucocorticoid treatment on the development of SAT, are discussed

  1. Study of in vivo movement of globulin-S

    International Nuclear Information System (INIS)

    Kubo, Junji; Kiyoki, Mamoru; Miura, Shuji; Fukushima, Hisashi; Naruchi, Tatsuyuki

    1978-01-01

    A quantity of human immune globulin in blood after globulin-S (S-sulfonated globulin ( GGS] for intravenous injection) was given to rat intravenously was 80% of administration dosage one hour the administration, 37% 24 hours, and 7% 29 days. The half life for 24 hours after the administration was about 17 hours. The half life after the distribution of globulin-S in blood and tissues had reached equilibrium was 13 days. The pool of human immune globulin in blood at this time was 54%. The peak of distribution amount of globulin-S in tissues appeared 6 hours after the administration in each tissues. The distribution amount in each tissues after that time changed in parallel with the concentration of globulin-S in blood. The pool of human immune globulin in tissues was 10% in the liver, 3% in the lung, and 2% in the kidney, 99% of sulfo was separated for 24 hours after the administration. The amount of ( 25 S] in blood decreased rapidly during a short time after the administration, and it decreased to 9% of ( 35 S] administered as 35 SGGS 2 hours after the administration. The amount of 35 SGGS distributed in each tissues reached its peak 2 hours after the administration, and hereafter it decreased rapidly in parallel with the amount of 35 SGGS distributed in blood. 85% and 11% of administered radioactivity were excreted in urine and stool, respectively, for 5 days after the intravenous administration of 35 SGGS. 7.7% of the administration dosage of 35 SGGS was excreted in bile for 24 hours after the administration. (Tsunoda, M.)

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

    Science.gov (United States)

    Souza, A J; Ferreira, A T S; Perales, J; Beghini, D G; Fernandes, K V S; Xavier-Filho, J; Venancio, T M; Oliveira, A E A

    2012-02-01

    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.

  3. 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.

  4. 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 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...... to be a sensitive marker of acute tissue injury and fatal outcome in humans. Patients with a low plasma concentration of Gc-globulin due to severe tissue injury might potentially benefit from infusions with purified Gc-globulin [1]. With an equine Gc-globulin assay, future studies will investigate the concentration...

  5. Labeling of human immune gamma globulin with sup(99m)Tc

    International Nuclear Information System (INIS)

    Wong, D.W.; Huang, J.T.

    1977-01-01

    Human immune serum gamma globulin and rabbit anti-Stap. aureus antibody have been successfully labeled with sup(99m)Tc at pH 7.4 with an average binding efficiency of 86 and 82%, respectively. The labeled proteins behave similarly to unlabeled gamma-globulin fraction in the normal human serum as demonstrated by protein electrophoresis. The biological half-time of sup(99m)Tc-gamma-globulin in dog has been determined to be 54 min for the fast component and 14.7 hr for a slower component. Immunological assays demonstrate no significant change in antibody activity after labeling process. (author)

  6. Admission levels of serum Gc-globulin

    DEFF Research Database (Denmark)

    Schiødt, F V; Bondesen, S; Petersen, I

    1996-01-01

    Gc-globulin scavenges actin released from necrotic hepatocytes to the extracellular space. In 77 patients with fulminant hepatic failure (FHF) (excluding patients treated with liver transplantation), admission levels of serum Gc-globulin and degree of complexing with monomeric actin (complex ratio...... in the same range as the KCH criteria. An advantage of Gc-globulin is that it gives an estimate of the outcome already on admission. Acute liver transplantation should be considered in FHF patients with Gc-globulin less than 100 mg/L....

  7. [Insulin-like growth factor-binding protein-1: a new biochemical marker of nonalcoholic fatty liver disease?].

    Science.gov (United States)

    Graffigna, Mabel Nora; Belli, Susana H; de Larrañaga, Gabriela; Fainboim, Hugo; Estepo, Claudio; Peres, Silvia; García, Natalia; Levalle, Oscar

    2009-03-01

    to assess the presence of nonalcoholic fatty liver disease in patients with risk factors for this pathology (obesity, dyslipidemia, metabolic syndrome and diabetes type 2) and to determine the role of insulin, HOMA index, insulin-like growth factor-binding protein-1, sex hormone-binding globulin and plasminogen activator inhibitor type 1, as biochemical markers. Ninety-one patients with risk factors for nonalcoholic fatty liver disease were evaluated. Serum transaminases, insulin, sex hormone-binding globulin, insulin-like growth factor-binding protein-1 and plasminogen activator inhibitor type 1 were measured. The diagnosis of fatty liver was performed by ultrasonography and liver biopsies were performed to 31 subjects who had steatosis by ultrasonography and high alanine aminotransferase. Nonalcoholic fatty liver disease was present in 65 out of 91 patients (71,4%). Liver biopsy performed to 31 subjects confirmed nonalcoholic steatohepatitis. Twenty-five patients had different degrees of fibrosis. Those individuals with fatty liver had higher waist circumference, serum levels of triglycerides, insulin and HOMA index, and lower serum insulin-like growth factor-binding protein-1 concentration. The degree ofhepatic steatosis by ultrasonography was positively correlated to waist circumference, triglycerides, insulin and HOMA index (p<0,003; p<0,003; p<0,002 and p<0,001, respectively), and was negatively correlated to HDL-cholesterol and insulin-like growth factor-binding protein-1 (p<0,025 and p<0,018, respectively). We found a high prevalence of NAFLD in patients with risk factors, most of them overweight or obese. Although SHBG and PAI-1 have a closely relationship to insulin resistance, they did not show to be markers of NAFLD. Regardless of low IGFBP-1 levels associated with NAFLD, serum IGFBP-1 measure is less accessible than insulin and triglycerides levels, HOMA index and waist circumference. Moreover, it is not a better marker for NAFLD than the above

  8. Polymeric competitive protein binding adsorbents for radioassay

    International Nuclear Information System (INIS)

    Adams, R.J.

    1976-01-01

    Serum protein comprising specific binding proteins such as antibodies, B 12 intrinsic factor, thyroxin binding globulin and the like may be copolymerized with globulin constituents of serum by the action of ethylchloroformate to form readily packed insoluble precipitates which, following purification as by washing, are eminently suited for employment as competitive binding protein absorbents in radioassay procedures. 10 claims, no drawings

  9. 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......-globulin concentrations in horses under clinical conditions have never previously been investigated. The Ph.D. project focuses on Gc-globulin as a prognostic marker in horses with acute abdominal pain....

  10. 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.

  11. THE COLLOIDAL BEHAVIOR OF SERUM GLOBULIN

    Science.gov (United States)

    Hitchcock, David I.

    1922-01-01

    1. The globulin prepared from ox serum by dilution and precipitation with carbon dioxide has been found, by electrometric titration experiments, to behave like an amphoteric electrolyte, reacting stoichiometrically with acids and bases. 2. The potential difference developed between a solution of globulin chloride, phosphate, or acetate and a solution of the corresponding acid, free from protein, separated from the globulin by a collodion membrane, was found to be influenced by hydrogen ion concentration and salt concentration in the way predicted by Donnan's theory of membrane equilibrium. In experiments with sodium globulinate and sodium hydroxide it was found that the potential difference could be similarly explained. 3. The osmotic pressure of such solutions could be qualitatively accounted for by the Donnan theory, but exhibited a discrepancy which is explicable by analogy with certain experiments of Loeb on gelatin. 4. The application of Loeb's theory of colloidal behavior, which had previously been found to hold in the case of gelatin, casein, egg albumin, and edestin, has thus been extended to another protein, serum globulin. PMID:19871977

  12. 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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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 1800 ppm). Rats were exposed 6 h/day for 1 or 4 weeks and kidneys excised approximately 18 h 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 (K d ) was estimated to be 1.27 × 10 −5 M. This K d 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)

  13. 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.

  14. Anti-tetanus toxoid antibodies in intravenous gamma globulin: an alternative to tetanus immune globulin.

    Science.gov (United States)

    Lee, D C; Lederman, H M

    1992-09-01

    The levels of anti-tetanus toxoid IgG antibodies were measured in 29 lots of intravenous gamma globulin (IVIG). The antibody levels varied from 4 to 90 IU/mL (geometric mean, 18.6; 90% confidence interval, 9.7-35.7). The variation from manufacturer to manufacturer accounted for most of the observed differences among lots; there was relatively little variability among multiple lots from a single manufacturer. IVIG may be an acceptable alternative to horse or human tetanus immune globulin.

  15. Extraction and characterization of chickpea (Cicer arietinum) albumin and globulin.

    Science.gov (United States)

    Liu, L H; Hung, T V; Bennett, L

    2008-06-01

    Albumin and globulin fractions of 1 Desi and 2 Kabuli varieties of chickpeas (Cicer arietinum) were extracted with water and salt solutions (K(2)SO(4) and NaCl). The extractable yields and particularly the albumin-globulin ratio varied greatly with the extraction medium and chickpea variety. Depending on the procedure employed, albumin could be extracted as a major fraction of chickpea proteins. Higher levels of essential amino acids and sulfur containing amino acids were found in albumins than in globulins of all chickpeas investigated. The common structural characteristics of both Kabuli and Desi chickpea albumins and globulins were clearly identified by densitometric profiles of their sodium dodecyl sulfate polyacrylamide gel patterns. Albumins contained subunits with higher molecular weights than those of globulins. The in vitro digestibility of the chickpea proteins by papain, pepsin, chymotrypsin, and trypsin indicated that globulins were more susceptible to proteolytic hydrolysis.

  16. Genetics Home Reference: inherited thyroxine-binding globulin deficiency

    Science.gov (United States)

    ... conditions appear to be more common in the Australian Aborigine population and in the Bedouin population of ... API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & Players U.S. Department of ...

  17. RSV Test

    Science.gov (United States)

    ... Sex Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia coli Sickle Cell Tests Sirolimus Smooth Muscle Antibody (SMA) ... University Medical Center, LAB Letter [On-line newsletter]. PDF available for download at http://www.stanfordhospital.com/ ...

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

    NARCIS (Netherlands)

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

    2017-01-01

    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

  19. 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 Immune...

  20. 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....102 Manufacture of Immune Globulin (Human). (a) Processing method. The processing method shall be one...

  1. Sex-specific metabolic profiles of androgens and its main binding protein SHBG in a middle aged population without diabetes

    DEFF Research Database (Denmark)

    Piontek, Uwe; Wallaschofski, Henri; Kastenmüller, Gabi

    2017-01-01

    The role of androgens in metabolism with respect to sex-specific disease associations is poorly understood. Therefore, we aimed to provide molecular signatures in plasma and urine of androgen action in a sex-specific manner using state-of-the-art metabolomics techniques. Our study population...

  2. 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...

  3. 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

    2012-01-01

    OBJECTIVE: 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. METHODS: A nested case-control study was conducted within the ...... and baseline HRT users. More studies are needed to support the findings for HRT users and to further investigate estrogen levels in relation to estrogen receptor-specific breast cancer and other histological and molecular subtypes.......OBJECTIVE: 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. METHODS: A nested case-control study was conducted within...... logistic regression yielded incidence rate ratios and 95 % confidence intervals for exposures analyzed continuously and categorically in models adjusted for potential confounders. RESULTS: Modest direct associations were identified between estrogen levels and breast cancer incidence among both never...

  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. Questioning the role of actinfree Gc-Globulin as actin scavenger in neurodegenerative central nervous system disease: relationship to S-100B levels and blood-brain barrier function.

    Science.gov (United States)

    Gressner, Olav A; Schifflers, Marie-Claire; Kim, Philipp; Heuts, Leo; Lahme, Birgit; Gressner, Axel M

    2009-02-01

    Preliminary studies report on significantly higher levels of the major cytoskeleton protein actin in CSF of patients with neurodegenerative conditions and that the dynamics of these levels obviously correlates with disease progression and clinical disability. One of the primary functions of actinfree Gc-Globulin is to bind and neutralize extracellular monomeric actin, released into the circulation by necrotic or ruptured cells, and thus ameliorating the clinical outcome in situations of severe organ damage. This is the first study to investigate actinfree Gc-Globulin and S100-B levels (as reliable marker of neurodegeneration) in paired CSF and serum samples of patients with multietiological CNS diseases. 42% of all patients with CNS disease displayed serum concentrations of actinfree Gc-Globulin above the established reference range. CSF concentrations of actinfree Gc-Globulin and S100-B were positively correlated with the severity of blood-brain barrier (BBB) dysfunction. Furthermore, patients with severe BBB dysfunction presented a higher percentage of intrathecal synthesis of actinfree Gc-Globulin compared to patients with mild to moderate dysfunction and to patients with normal BBB function. Representative longitudinal data from selected patients demonstrated an inverse behaviour of actinfree Gc-Globulin and S100-B CSF concentrations, suggesting a consumption of the actin scavenger capacity of Gc-Globulin in times of increased neuronal damage. This presumption was supported by the fact that those conditions associated with a severe neuronal damage, in particular CNS trauma, and highest S100-B concentrations simultaneously displayed lowest actinfree Gc-Globulin levels, and thus residual actin binding capacity of Gc-Globulin. In summary, our data propose a function of actinfree Gc-Globulin also in the clearance of actin filaments from CSF of patients with neuronal damage. However, active recruitment of hepatic derived actinfree Gc-Globulin to the site of CNS

  6. Physicochemical, functional and angiotensin converting enzyme inhibitory properties of amaranth (Amaranthus hypochondriacus) 7S globulin.

    Science.gov (United States)

    Quiroga, Alejandra V; Aphalo, Paula; Ventureira, Jorge L; Martínez, E Nora; Añón, María C

    2012-01-30

    Amaranth 7S globulin is a minor globulin component and its impact on the properties of an amaranth protein ingredient depends on its proportion in the variety of amaranth being considered. Some physicochemical, functional and angiotesin I-converting enzyme (ACE) inhibitory properties of amaranth vicilin were studied in this work and compared with the 11S globulin. Fluorescence spectroscopy results indicated that 7S globulin tryptophans were more exposed to the solvent and, by calorimetry, the 7S globulin denaturation temperature (T(d) ) was found lower than the 11S globulin T(d) , suggesting a more flexible structure. The 7S globulin surface hydrophobicity was higher than that of the 11S globulin, which is in agreement with the better emulsifying properties of the 7S globulin. The solubility in neutral buffer of the 7S globulin (851 ± 25 g kg(-1) ) was also higher than that of the 11S globulin (195 ± 6 g kg(-1) ). Bioinformatic analyses showed the presence of ACE inhibitory peptides encrypted in 7S tryptic sequences and peptides released after in vitro gastrointestinal digestion showed a high ACE-inhibitory capacity (IC(50) = 0.17 g L(-1) ), similar to that of 11S globulin peptides. Compared with the 11S globulin, the 7S globulin presents similar ACE inhibitory activity and some functional advantages, better solubility and emulsifying activity, which suits some food requirements. The functional behavior has been related with the structural properties. Copyright © 2011 Society of Chemical Industry.

  7. Dynamic changes of horse serum T-globulin immunization with snake venoms, tetanus and diphtheria toxoids.

    Science.gov (United States)

    Lee, H F; Lee, J D; Lee, Y C

    1979-12-01

    In course of immunizing horses with snake venoms, tetanus and diphtheria toxoids, a new serum component, T-globulin, was formed and migrated between the beta- and gamma-globulins. The T-globulin content was parallel with the antibody titre after the middle course of immunization. There were many components in snake antivenin and T-globulin was composed of most of those components. The components of diphtheria T-globulin were the same as those of crude antitoxin and tetanus T-globulin except one precipitin.

  8. Antitumor effect of degalactosylated gc-globulin on orthotopic grafted lung cancer in mice.

    Science.gov (United States)

    Hirota, Keiji; Nakagawa, Yoshinori; Takeuchi, Ryota; Uto, Yoshihiro; Hori, Hitoshi; Onizuka, Shinya; Terada, Hiroshi

    2013-07-01

    Group-specific component (Gc)-globulin-derived macrophage-activating factor (GcMAF) generated by a cascade of catalytic reactions with deglycosidase enzymes exerts antitumor activity. We hypothesized that degalactosyl Gc-globulin (DG3), a precursor of GcMAF, also plays a role in recovery from cancer as well as GcMAF due to progression of deglycosylation by generally resident sialidases and mannosidases. We prepared the subtypes of DG3, such as 1f1f and 1s1s and its 22 homodimers, by using vitamin D3-binding Sepharose CL-6B and examined their antitumor activity in mice bearing Lewis lung carcinoma cells, by counting the number of nodules formed in their lungs. Antitumor activity of DG3 was observed regardless of its subtype, being equivalent to that of GcMAF. The injection route of DG3 affected its antitumor activity, with subcutaneous and intramuscular administration being more favorable than the intraperitoneal or intravenous route. In order to obtain significant antitumor activity, more than 160 ng/kg of DG3 were required. DG3 proved to be promising as an antitumor agent, similarly to GcMAF.

  9. The proteomic analysis of barley albumins and globulins

    Czech Academy of Sciences Publication Activity Database

    Laštovičková, Markéta; Bobálová, Janette

    2008-01-01

    Roč. 102, č. 15 (2008), s709-s711 ISSN 1803-2389. [Meeting on Chemistry and Life /4./. Brno, 09.09.2008-11.09.2008] R&D Projects: GA MŠk 1M0570 Institutional research plan: CEZ:AV0Z40310501 Keywords : barley * albumins * globulins Subject RIV: CB - Analytical Chemistry, Separation

  10. Heterogeneity in the seed globulin and albumin fractions from ...

    African Journals Online (AJOL)

    Successful fractionation of albumin, globulin and vicilin fractions from dry seeds of African yam bean (Sphenostylis stenocarpa) was achieved using established procedures for preparation of legume seed proteins. The resulting polypeptides were separated by native polyacrylamide gel electrophoresis under both reducing ...

  11. Serum total protein, albumin and globulin levels in Trypanosoma ...

    African Journals Online (AJOL)

    The effect of orally administered Scoparia dulcis on Trypanosoma brucei-induced changes in serum total protein, albumin and globulin were investigated in rabbits over a period of twenty eight days. Results obtained show that infection resulted in hyperproteinaemia, hyperglobulinaemia and hypoalbuminaemia. However ...

  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. Ultrastructural studies of human and rabbit alpha-M-globulins.

    Science.gov (United States)

    Bloth, B; Chesebro, B; Svehag, S E

    1968-04-01

    Electron micrographs of isolated human alpha(2)M-molecules, obtained by the negative contrast technique, revealed morphologically homogenous structures resembling a graceful monogram of the two letters H and I. The modal values for the length and width of the alpha(2)M particles were 170 A and 100 A, respectively. Purified rabbit alphamacroglobulins contained about 80% alpha(1)M- and 20% alpha(2)M-globulins. The isolated rabbit alpha(1)M- and alpha(2)M-molecules were morphologically indistinguishable from one another and from human alpha(2)M-molecules. Preliminary immunoprecipitation studies demonstrated that the two rabbit alphaM-globulins were antigenically different. Sedimentation constant determinations gave s(20, w) values of 18.8 and 18.2 for rabbit alpha(1)M and alpha(2)M, respectively.

  14. Fibroblast receptor for cell-substratum adhesion: studies on the interaction of baby hamster kidney cells with latex beads coated by cold insoluble globulin (plasma fibronectin)

    OpenAIRE

    1980-01-01

    Studies were carried out on the interactions of uncharged latex beads (0.76 micrometer) with baby hamster kidney cells. Binding of beads to the cells occurred if the beads were coated by cold insoluble globulin (CIG) (plasma fibronectin) but not if the beads were coated by bovine albumin. Bovine albumin-coated beads did not bind to the cells even in the presence of excess CIG in the incubation medium. Binding of beads occurred randomly over the entire surfaces of cells in suspension. However,...

  15. Differential dissociation micromethod for the investigation of binding of metandrostenolone (Nerobol) to plasma proteins

    International Nuclear Information System (INIS)

    Bojadzsieva, Milka; Kocsar, Laszlo; Kremmer, Tibor

    1985-01-01

    A micromethod was developed to determine the binding of anabolic streoids to plasma proteins. The new procedure combines precipitation with ammonium sulphate and differential dissociation. The binding parameters (association constant, specific binding capacity) are calculated on the basis of dissociation curves of sup(3)H-metandrostenolone from the precipitated sexual binding globuline. (L.E.)

  16. Differential dissociation micromethod for the investigation of binding of metandrostenolone (Nerobol) to plasma proteins

    Energy Technology Data Exchange (ETDEWEB)

    Bojadzsieva, M.; Kocsar, L. (Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszseguegyi Kutato Intezet, Budapest (Hungary)); Kremmer, T. (Orszagos Onkologiai Intezet, Budapest (Hungary))

    1985-01-01

    A micromethod was developed to determine the binding of anabolic steroids to plasma proteins. The new procedure combines precipitation with ammonium sulphate and differential dissociation. The binding parameters (association constant, specific binding capacity) are calculated on the basis of dissociation curves of sup(3)H-metandrostenolone from the precipitated sexual binding globuline.

  17. Interference of tolerance to human gamma globulin by synthetic polynucleotides

    International Nuclear Information System (INIS)

    Rey, O.A.; Azar, M.M.

    1975-01-01

    A complex of polyadenylic-polyuridylic acids effectively inhibits the in vivo production of immunologic tolerance to human gamma globulin in mice. Moreover, this effect can be obtained only when the polynucleotide complex is given within 4 hr after antigen administration. Reconstitution of irradiated mice with combinations of T and B cells originating from tolerant or previously untreated mice demonstrates that poly A:U is responsible for the adjuvant effect observed. Poly A:U exerts its adjuvant effect primarily upon T cells, while B cells remain essentially uninfluenced by the polynucleotides

  18. Outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine A

    Directory of Open Access Journals (Sweden)

    Marlene Pereira Garanito

    2014-09-01

    Conclusions: The present results confirm the poor response rate with rabbit antithymocyte globulin as first therapy in pediatrics patients, similar to what has been reported for patients of all ages. This confirmation is problematic in Brazil, given the lack of horse antithymocyte globulin in many markets outside the United States.

  19. 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

    2017-07-01

    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 human leukocyte antigen (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 aplastic anemia. Copyright© 2017 Ferrata Storti Foundation.

  20. The molecular biology and biochemistry of rice endosperm α-globulin

    International Nuclear Information System (INIS)

    Shorrosh, B.S.

    1989-01-01

    The author's first objective was to isolate a cDNA clone that encodes the rice endosperm α-globulin. Purified antibodies against a rice storage protein, α-globulin, were used to screen a λgt11 cDNA expression library constructed from immature rice seed endosperm. The cDNA insert of clone 4A1 (identified by antibody screening) was used as a probe to identify long cDNA inserts in the library. The deduced amino acid sequence of clone A3-12 cDNA insert (identified by cDNA screening) contained the amino acid sequences of three cyanogen bromide peptides fragment of α-globulin. The calculated molecular weight and amino acid composition of the deduced amino acid sequence were similar to the α-globulin protein. Northern blot analysis indicated that mRNA of one size, approximately 1.0 kb, is expressed. Southern genomic blot analysis revealed one band with EcoRI or Hind III digestion. Cell-free translation and immunoprecipitation showed that the initial translation product is approximately 2,000 daltons larger than the mature protein. The amino acid sequence of α-globulin revealed limited regions of similarities with wheat storage proteins. The author concludes that the cDNA insert in clone A3-12 contained the entire coding region of α-globulin protein and that α-globulin is encoded by a single gene. My second objective was to inhibit the degradation of α-globulin in the salt extract of rice flour. The salt extract of rice flour contained an acid protease whose optimal pH was 3 for 3 H-casein hydrolysis. A polypeptide with molecular weight of 20,000 was immunologically reactive with α-globulin antibodies and is produced by limited proteolysis in the extract. Pepstatin inhibited the proteolysis of 3H-casein and slowed the proteolysis of α-globulin

  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. Unique Approaches to Androgen Effects on Prostate Cancer

    National Research Council Canada - National Science Library

    Rosner, W; Kahn, S. M

    2007-01-01

    Sex hormone-binding globulin (SHBG) is a plasma protein that binds andrngens and it acts as a transducer of androgen signaling at the plasma membrane of prostate cancer cells The human prostate cancer cell line LNCaP in addition...

  3. Serum protein inhibition of thyrotropin binding to human thyroid tissue

    International Nuclear Information System (INIS)

    Beall, G.N.; Chopra, I.J.; Solomon, D.H.; Kruger, S.R.

    1978-01-01

    We used a modificaton of the TSH radioreceptor assay to detect TSH-binding inhibition (TBI) activity in serum and serum fractions from normal subjects and patients with Graves' disease. TBI activity is present in normal IgG prepared by DEAE-Sephadex chromatography and in normal globulins prepared by precipitation at 1.6 M ammonium sulfate. Other normal serum proteins also had TBI activity when large concentrations were tested. Gel filtration chromatography and powder block electrophoresis were used to prepare fractions of normal and Graves' disease sera. In these fractions from normal serum, TBI activity was found in both γ-globulin and α-globulin-albumin fractions electrophoretically and in both 7S and 4S peaks from gel filtration. TBI activity from Graves' disease patients' sera was similarly distributed, but relatively more TBI accompanied the electrophoretic γ-globulins. Sepharose Protein-A and anti-IgG were used as immunoabsorbents to isolate and purify IgG from normal and Graves' disease sera. TBI activity in IgG was proportional to the IgG concentration, indicating that the TBI which migrates as a γ-globulin electrophoretically is an IgG and thus may possibly be an antibody. Inhibitory activity found in normal serum globulins and in the non-IgG fractions of both normal and abnormal sera seriously interferes with attempts to use the TSH radioreceptor assay to study the hypothesized anti-TSH receptor antibody in the serum of patients with Graves' disease

  4. Meta-analysis of treatment with rabbit and horse antithymocyte globulin for aplastic anemia.

    Science.gov (United States)

    Hayakawa, Jin; Kanda, Junya; Akahoshi, Yu; Harada, Naonori; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Yamazaki, Rie; Kako, Shinichi; Kanda, Yoshinobu

    2017-05-01

    Aplastic anemia patients who received rabbit antithymocyte globulin exhibited response and survival rates inferior to those who received horse antithymocyte globulin in several studies. Therefore, we conducted a meta-analysis to compare rabbit and horse antithymocyte globulin as immunosuppressive therapy for aplastic anemia. We searched online databases for studies that compared antithymocyte globulin regimens as first-line treatment for aplastic anemia, including both randomized and non-randomized controlled trials. The early mortality rate at 3 months and overall response rate at 6 months were evaluated. Thirteen studies were included in the analysis. The risk ratio (RR) of early mortality for rabbit vs. horse antithymocyte globulin was 1.33 [95% confidence interval (CI) 0.69-2.57; P = 0.39], with significant heterogeneity. A sensitivity analysis suggested higher early mortality rate in patients who received rabbit antithymocyte globulin. The overall response rate was significantly higher in patients who received horse antithymocyte globulin (RR 1.27; 95% CI 1.05-1.54; P = 0.015). In conclusion, in aplastic anemia patients treated with ATG, early mortality rate was not significantly different in patients receiving horse or rabbit ATG, although a sensitivity analysis showed higher early mortality in the rabbit ATG group. Horse ATG was associated with significantly higher response rate than rabbit ATG.

  5. Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Tobias Roider

    2016-12-01

    Full Text Available Antithymocyte globulin (ATG is used in the prevention of graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. It is generally accepted that ATG mediates its immunosuppressive effect primarily via depletion of T cells. Here, we analyzed the impact of ATG-Fresenius (now Grafalon® on human monocyte-derived dendritic cells (DC. ATG induced a semi-mature phenotype in DC with significantly reduced expression of CD14, increased expression of HLA-DR, and intermediate expression of CD54, CD80, CD83, and CD86. ATG-DC showed an increase in IL-10 secretion but no IL-12 production. In line with this tolerogenic phenotype, ATG caused a significant induction of indoleamine 2,3-dioxygenase expression and a concomitant increase in levels of tryptophan metabolites in the supernatants of DC. Further, ATG-DC did not induce the proliferation of allogeneic T cells in a mixed lymphocyte reaction but actively suppressed the T cell proliferation induced by mature DC. These data suggest that besides its well-known effect on T cells, ATG modulates the phenotype of DC in a tolerogenic way, which might constitute an essential part of its immunosuppressive action in vivo.

  6. Thermal denaturation of sunflower globulins in low moisture conditions

    International Nuclear Information System (INIS)

    Rouilly, A.; Orliac, O.; Silvestre, F.; Rigal, L.

    2003-01-01

    DSC analysis in pressure resisting pans of sunflower oil cake makes appear the endothermic peak of sunflower globulins denaturation. Its temperature decreases from 189.5 to 119.9 deg. C while the corresponding enthalpy increases from 2.6 to 3.3 J/g of sample, or from 6.7 to 12.2 J/g of dry protein, when the samples moisture content varies from 0 to 30.0% of the total weight. The plot of the denaturation temperature versus the moisture content is not linear but has a rounded global shape and seems to follow the hydration behavior of the proteins, modeled with the sorption isotherm. As it can be seen on scanning electron microscopy (SEM) micrographs, protein corpuscles 'melt' after such a thermal treatment and large aggregates form by coagulation. Moisture dependence of the 'fusion' temperature of native proteic organization, in low moisture conditions, offers so a new characterization method for the use of vegetable proteins in agro-materials

  7. Thermal denaturation of sunflower globulins in low moisture conditions

    Energy Technology Data Exchange (ETDEWEB)

    Rouilly, A.; Orliac, O.; Silvestre, F.; Rigal, L

    2003-03-05

    DSC analysis in pressure resisting pans of sunflower oil cake makes appear the endothermic peak of sunflower globulins denaturation. Its temperature decreases from 189.5 to 119.9 deg. C while the corresponding enthalpy increases from 2.6 to 3.3 J/g of sample, or from 6.7 to 12.2 J/g of dry protein, when the samples moisture content varies from 0 to 30.0% of the total weight. The plot of the denaturation temperature versus the moisture content is not linear but has a rounded global shape and seems to follow the hydration behavior of the proteins, modeled with the sorption isotherm. As it can be seen on scanning electron microscopy (SEM) micrographs, protein corpuscles 'melt' after such a thermal treatment and large aggregates form by coagulation. Moisture dependence of the 'fusion' temperature of native proteic organization, in low moisture conditions, offers so a new characterization method for the use of vegetable proteins in agro-materials.

  8. Genomic organization of the rat alpha 2u-globulin gene cluster.

    Science.gov (United States)

    McFadyen, D A; Addison, W; Locke, J

    1999-05-01

    The alpha 2u-globulin are a group of similar proteins, belonging to the lipocalin superfamily of proteins, that are synthesized in a subset of secretory tissues in rats. The many alpha 2u-globulin isoforms are encoded by a multigene family that exhibits extensive homology. Despite a high degree of sequence identity, individual family members show diverse expression patterns involving complex hormonal, tissue-specific, and developmental regulation. Analysis suggests that there are approximately 20 alpha 2u-globulin genes in the rat genome. We have used fluorescence in situ hybridization (FISH) to show that the alpha 2u-globulin genes are clustered at a single site on rat Chromosome (Chr) 5 (5q22-24). Southern blots of rat genomic DNA separated by pulsed field gel electrophoresis indicated that the alpha 2u-globulin genes are contained on two NruI fragments with a total size of 880 kbp. Analysis of three P1 clones containing alpha 2u-globulin genes indicated that the alpha 2u-globulin genes are tandemly arranged in a head-to-tail fashion. The organization of the alpha 2u-globulin genes in the rat as a tandem array of single genes differs from the homologous major urinary protein genes in the mouse, which are organized as tandem arrays of divergently oriented gene pairs. The structure of these gene clusters may have consequences for the proposed function, as a pheromone transporter, for the protein products encoded by these genes.

  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. 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.

  11. Concepts for the assay of unbound thyroxine (FT4) and thyroxine binding globulin (TBG)

    International Nuclear Information System (INIS)

    Odstrchel, G.; Hertl, W.; Ward, F.B.; Travis, K.; Lindner, R.E.; Mason, R.D.

    1977-01-01

    Two new concepts for the assay of thyroid related substances are presented. One assay (FT 4 ) is based on a kinetic measurement of T 4 as it desorbs from binder proteins onto solid-phase T 4 antibody. This reaction can be described by a second order rate equation; r = k (IMA) (FT 4 ). The assay is rapid (2 hours) and gives good agreement (sigma = 0.92) with equilibrium dialysis and a normal range of 0.9 - 2.3 ng/dl. This assay uses a small sample size (25 μl) and is unaffected by drugs such as aspirin and dilantin. Pregnant and estrogen treated women gave normal FT 4 values. A new method for the measurement of functionally active TEG is also presented. In this case the labeled T 4 is partitioned between bovine serum albumin and the patient's samples. The complex is then removed from solution by solid-phase anti-TBG. A curve remiscent of an immunoradiometric assay is obtained. The assay has a sensitivity of 4 μg/ml and is unaffected by aspirin, dilantin or the patient's T 4 concentrations. Correlation with 'rocket' electrophoresis is 0.90. The normal range was 20 +- 7 μg/ml with pregnant women giving values greater than 30 μg/ml. Five hereditary deficient patients gave a value equivalent to zero TBG concentration. (orig.) [de

  12. 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 Kold; 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....

  13. 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

  14. Preliminary results of a new radioimmunoassay for thyroxine binding globulin (T.B.G.)

    International Nuclear Information System (INIS)

    Bisset, J.-P.; Sauvan, R.; Roux, F.; Hourtoule, P.

    1978-01-01

    A radioimmunoassay for the accurate measurement of T.B.G., developed by Crouzat-Reynes, was used to perform T.B.G. concentration in sera of euthyroid subjects in different clinical situations, in hypothyroid and hyperthyroid patients. In normal control, the T.B.G. concentration was not different from men and women, from young and old subjects. On the other hand, in women either pregnant or receving oral contraception, the T.B.G. levels were significantly higher than euthyro subjects. Cirrhosis of the liver and liver carcinoma were without apparent effect on T.B.G. levels because it was a too few number of patients and the group was too heterogeneous. In the group of hypothyroid and hyperthyroid patients, the T.B.G. serum concentrations were not significantly different from normal. The ratio T4/T.B.G. as I.T.L. (T4 x T3 uptake) permit to bring back in normal range T4 levels changed by extrathyroidal process; however, this ratio seems to be less interesting than standard I.T.L. The T.B.G. assay has not to be considered only as a substitution of T3 uptake because they do not study the same parameters [fr

  15. 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.......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....

  16. Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin.

    Science.gov (United States)

    Vora, Neil M; Orciari, Lillian A; Bertumen, J Bradford; Damon, Inger; Ellison, James A; Fowler, Vance G; Franka, Richard; Petersen, Brett W; Satheshkumar, P S; Schexnayder, Stephen M; Smith, Todd G; Wallace, Ryan M; Weinstein, Susan; Williams, Carl; Yager, Pamela; Niezgoda, Michael

    2018-02-09

    Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody…test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG.

  17. Increased serum cortisol binding in chronic active hepatitis

    International Nuclear Information System (INIS)

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG

  18. Testosterone and BMD in Elite Male Lightweight Rowers

    DEFF Research Database (Denmark)

    Vinther, A.; Christiansen, E.; Ekdahl, C.

    2008-01-01

    ), free testosterone (IFT), dihydrotestosterone (DHT) and sex hormone binding globulin (SHBG) and additional parameters related to bone metabolism were measured. Plasma concentrations of TT, FT and DHT were in the lower part of the normal range, while BMD was close to or above normal. BMD of total body...

  19. Complement Test

    Science.gov (United States)

    ... Salicylates Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia ... and forming complexes that respond to infections, non-self tissues (transplants), dead cells ... KJ. Complement determinations in human disease. Ann Allergy Asthma Immunol . 2004; ...

  20. 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

  1. Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Ose, Jennifer; Fortner, Renée T.; Rinaldi, Sabina; Schock, Helena; Overvad, Kim; Tjonneland, Anne; Hansen, Louise; Dossus, Laure; Fournier, Agnes; Baglietto, Laura; Romieu, Isabelle; Kuhn, Elisabetta; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Masala, Giovanna; Sieri, Sabina; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Ramon Quiros, Jose; Obõn-Santacana, Mireia; Larrañaga, Nerea; Chirlaque, María Dolores; Sánchez, María José; Barricarte, Aurelio; Peeters, Petra H.; Bueno-De-Mesquita, H. B.; Onland-Moret, N. Charlotte; Brändstedt, Jenny; Lundin, Eva; Idahl, Annika; Weiderpass, Elisabete; Gram, Inger T.; Lund, Eiliv; Kaw, Kay Tee; Travis, Ruth C.; Merritt, Melissa A.; Gunther, Marc J.; Riboli, Elio; Kaaks, Rudolf

    2015-01-01

    The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology,

  2. Hypogonadism in patients with chronic obstructive pulmonary ...

    African Journals Online (AJOL)

    ... free testosterone (FT), sex hormone binding globulins (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and 17b estradiol levels (E2), the exercise capacity (6-minute walk distance (6MWT)) and quadriceps muscle force (One repetition maximum (1RM) and EMG). COPD patients underwent spirometry.

  3. Biosensor-based detection of reduced sex hormone-binding globulin binding capacities in response to growth-promoter administrations.

    NARCIS (Netherlands)

    Mooney, M.H.; Bergwerff, A.A.; van Meeuwen, J.A.; Luppa, P.B.; Elliott, C.T.

    2009-01-01

    Growth-promoting agents are illicitly used during animal rearing processes and the detection of their use is limited by new compounds and dosing practices that limit the efficiency of current testing which is based on residue analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and

  4. Lack of Globulin Synthesis during Seed Development Alters Accumulation of Seed Storage Proteins in Rice

    Directory of Open Access Journals (Sweden)

    Hye-Jung Lee

    2015-06-01

    Full Text Available The major seed storage proteins (SSPs in rice seeds have been classified into three types, glutelins, prolamins, and globulin, and the proportion of each SSP varies. It has been shown in rice mutants that when either glutelins or prolamins are defective, the expression of another type of SSP is promoted to counterbalance the deficit. However, we observed reduced abundances of glutelins and prolamins in dry seeds of a globulin-deficient rice mutant (Glb-RNAi, which was generated with RNA interference (RNAi-induced suppression of globulin expression. The expression of the prolamin and glutelin subfamily genes was reduced in the immature seeds of Glb-RNAi lines compared with those in wild type. A proteomic analysis of Glb-RNAi seeds showed that the reductions in glutelin and prolamin were conserved at the protein level. The decreased pattern in glutelin was also significant in the presence of a reductant, suggesting that the polymerization of the glutelin proteins via intramolecular disulfide bonds could be interrupted in Glb-RNAi seeds. We also observed aberrant and loosely packed structures in the storage organelles of Glb-RNAi seeds, which may be attributable to the reductions in SSPs. In this study, we evaluated the role of rice globulin in seed development, showing that a deficiency in globulin could comprehensively reduce the expression of other SSPs.

  5. Effect of Co-60 irradiation on hyperimmune antimeningococcus globulins-gamma

    International Nuclear Information System (INIS)

    Galguera, M.; Le Riverand, E.; Padron, S.

    1990-01-01

    Globulins-gamma from voluntary blood donors immunized with the Cuban BC antimeningococcus vaccine is now being used in our country for the treatment of the meningococcus disease. This study of the effect of Co-60 irradiation on antimeningococcus globulins-gamma was carried out to try to eliminate the inconvenience shown by the traditionally used sterilization procedures (losses in the filter and persistence of viral contamination). globulins-gamma was obtained by ethanol fractionation and was irradiated at a different dose in solution with different stabilizers and it was also lyophilized. Results of the chemical controls carried out lead to the conclusion that it is possible to use radiosterilization on this product in a lyophilized form. The preservation of bactericidal activity, even after the highest irradiation doses, confirms the above mentioned. 13 refs

  6. CONFORMATION CHANGES OF HUMAN SERUM γ–GLOBULIN IN THE PRESENCE OF ZINC IONS

    Directory of Open Access Journals (Sweden)

    S. B. Cheknev

    2005-01-01

    Full Text Available Abstract. Conformational changes of human serum γ–globulin during interaction with the zinc ions were studied in a solution. It has been shown that the presence of zinc in over its physiological concentrations led to increase in optical density across the whole spectrum of γ–globulin ultraviolet absorption. On the contrary, hypochromia in the spectrum was registered after interaction of the protein with zinc used in subphisiological concentrations. Possible role of divalent metal cations in changes in conformation of the blood serum γ–globulins, and thereby in regulation of their effector functions was discussed. (Med. Immunol., 2005, vol.7, № 4, pp. 375–380

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

    Science.gov (United States)

    Dziuba, Jerzy; Szerszunowicz, Iwona; Nałęcz, Dorota; Dziuba, Marta

    2014-01-01

    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. 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. 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. Two-dimensional gel electrophoresis proved to be a useful tool for identifying pea proteins. Patterns of spots with similar isoelectric

  8. Detection of haplotypes associated with prenatal death in dairy cattle and identification of deleterious mutations in GART, SHBG and SLC37A2.

    Directory of Open Access Journals (Sweden)

    Sébastien Fritz

    Full Text Available The regular decrease of female fertility over time is a major concern in modern dairy cattle industry. Only half of this decrease is explained by indirect response to selection on milk production, suggesting the existence of other factors such as embryonic lethal genetic defects. Genomic regions harboring recessive deleterious mutations were detected in three dairy cattle breeds by identifying frequent haplotypes (>1% showing a deficit in homozygotes among Illumina Bovine 50k Beadchip haplotyping data from the French genomic selection database (47,878 Holstein, 16,833 Montbéliarde, and 11,466 Normande animals. Thirty-four candidate haplotypes (p<10(-4 including previously reported regions associated with Brachyspina, CVM, HH1, and HH3 in Holstein breed were identified. Haplotype length varied from 1 to 4.8 Mb and frequencies from 1.7 up to 9%. A significant negative effect on calving rate, consistent in heifers and in lactating cows, was observed for 9 of these haplotypes in matings between carrier bulls and daughters of carrier sires, confirming their association with embryonic lethal mutations. Eight regions were further investigated using whole genome sequencing data from heterozygous bull carriers and control animals (45 animals in total. Six strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina, SLC35A3 (CVM, APAF1 (HH1 and three novel mutations with very damaging effect on the protein structure, according to SIFT and Polyphen-2, were detected in GART, SHBG and SLC37A2 genes. In conclusion, this study reveals a yet hidden consequence of the important inbreeding rate observed in intensively selected and specialized cattle breeds. Counter-selection of these mutations and management of matings will have positive consequences on female fertility in dairy cattle.

  9. Detection of haplotypes associated with prenatal death in dairy cattle and identification of deleterious mutations in GART, SHBG and SLC37A2.

    Science.gov (United States)

    Fritz, Sébastien; Capitan, Aurelien; Djari, Anis; Rodriguez, Sabrina C; Barbat, Anne; Baur, Aurélia; Grohs, Cécile; Weiss, Bernard; Boussaha, Mekki; Esquerré, Diane; Klopp, Christophe; Rocha, Dominique; Boichard, Didier

    2013-01-01

    The regular decrease of female fertility over time is a major concern in modern dairy cattle industry. Only half of this decrease is explained by indirect response to selection on milk production, suggesting the existence of other factors such as embryonic lethal genetic defects. Genomic regions harboring recessive deleterious mutations were detected in three dairy cattle breeds by identifying frequent haplotypes (>1%) showing a deficit in homozygotes among Illumina Bovine 50k Beadchip haplotyping data from the French genomic selection database (47,878 Holstein, 16,833 Montbéliarde, and 11,466 Normande animals). Thirty-four candidate haplotypes (pHH3 in Holstein breed were identified. Haplotype length varied from 1 to 4.8 Mb and frequencies from 1.7 up to 9%. A significant negative effect on calving rate, consistent in heifers and in lactating cows, was observed for 9 of these haplotypes in matings between carrier bulls and daughters of carrier sires, confirming their association with embryonic lethal mutations. Eight regions were further investigated using whole genome sequencing data from heterozygous bull carriers and control animals (45 animals in total). Six strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina), SLC35A3 (CVM), APAF1 (HH1) and three novel mutations with very damaging effect on the protein structure, according to SIFT and Polyphen-2, were detected in GART, SHBG and SLC37A2 genes. In conclusion, this study reveals a yet hidden consequence of the important inbreeding rate observed in intensively selected and specialized cattle breeds. Counter-selection of these mutations and management of matings will have positive consequences on female fertility in dairy cattle.

  10. Detection of Haplotypes Associated with Prenatal Death in Dairy Cattle and Identification of Deleterious Mutations in GART, SHBG and SLC37A2

    Science.gov (United States)

    Fritz, Sébastien; Capitan, Aurelien; Djari, Anis; Rodriguez, Sabrina C.; Barbat, Anne; Baur, Aurélia; Grohs, Cécile; Weiss, Bernard; Boussaha, Mekki; Esquerré, Diane; Klopp, Christophe; Rocha, Dominique; Boichard, Didier

    2013-01-01

    The regular decrease of female fertility over time is a major concern in modern dairy cattle industry. Only half of this decrease is explained by indirect response to selection on milk production, suggesting the existence of other factors such as embryonic lethal genetic defects. Genomic regions harboring recessive deleterious mutations were detected in three dairy cattle breeds by identifying frequent haplotypes (>1%) showing a deficit in homozygotes among Illumina Bovine 50k Beadchip haplotyping data from the French genomic selection database (47,878 Holstein, 16,833 Montbéliarde, and 11,466 Normande animals). Thirty-four candidate haplotypes (p<10−4) including previously reported regions associated with Brachyspina, CVM, HH1, and HH3 in Holstein breed were identified. Haplotype length varied from 1 to 4.8 Mb and frequencies from 1.7 up to 9%. A significant negative effect on calving rate, consistent in heifers and in lactating cows, was observed for 9 of these haplotypes in matings between carrier bulls and daughters of carrier sires, confirming their association with embryonic lethal mutations. Eight regions were further investigated using whole genome sequencing data from heterozygous bull carriers and control animals (45 animals in total). Six strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina), SLC35A3 (CVM), APAF1 (HH1) and three novel mutations with very damaging effect on the protein structure, according to SIFT and Polyphen-2, were detected in GART, SHBG and SLC37A2 genes. In conclusion, this study reveals a yet hidden consequence of the important inbreeding rate observed in intensively selected and specialized cattle breeds. Counter-selection of these mutations and management of matings will have positive consequences on female fertility in dairy cattle. PMID:23762392

  11. Studies on a possible using of penicillin and specific globulin for treatment of Siberia ulcer infection in irradiated animals

    International Nuclear Information System (INIS)

    Strel'nikov, V.A.; Mal'tsev, V.N.

    1975-01-01

    The efficiency of anti-anthracic globulin and penicillin for treating infectious anthrax was compared in experiments on 160 guinea pigs and 400 white mice irradiated with sub-lethal doses of cobalt-60 gamma rays. It was found that penicillin retained its effectiveness in the irradiated animals whereas anti-anthracic globulin lost much of its therapeutic efficiency. (auth.)

  12. Immune globulins are effective in severe pediatric Guillain-Barré syndrome.

    Science.gov (United States)

    Shahar, E; Shorer, Z; Roifman, C M; Levi, Y; Brand, N; Ravid, S; Murphy, E G

    1997-01-01

    The effect of high-dose intravenous immune globulins was evaluated in an open prospective multicenter study of 26 children with severe Guillain-Barré syndrome. They presented with mild to moderate flaccid weakness of extremities, with cranial nerve involvement (20) and sensory impairment (22). All children rapidly deteriorated in 2-16 days (mean 6) to become bedridden, and 2 children also developed respiratory failure requiring artificial ventilation (Disability Grading Scale 4-5). Immune globulins were then administered at a total dose of 2 gm/kg, on 2 consecutive days, without adverse effects requiring discontinuation of therapy. Marked and rapid improvement was noted in 25 children, who improved by 1 to 2 Disability Grade Scales ventilator. Eighteen children recovered by 2 weeks. The rest recuperated in a period of four months, including a child who was artificially ventilated for 4 weeks. The uniform rapid improvement and recovery associated with immune globulins contrasts with the slow recovery course in severe natural cases. We conclude that immune globulins are effective and safe in severe childhood-onset Guillain-Barré syndrome and therefore may serve as the initial treatment of choice.

  13. Competitive adsorption of albumin and monoclonal immuno upsilon globulin molecules on polystyrene surfaces

    NARCIS (Netherlands)

    Elgersma, F.

    1990-01-01

    The subject of this thesis is proteins at interfaces. The main purpose of the work was to acquire more insight into the mechanism of adsorption of Bovine Serum Albumin (BSA) and monoclonal Immuno gamma Globulins (IgG's). both individually and in competition. Another aim was to achieve

  14. Overestimation of Albumin Measured by Bromocresol Green vs Bromocresol Purple Method: Influence of Acute-Phase Globulins.

    Science.gov (United States)

    Garcia Moreira, Vanessa; Beridze Vaktangova, Nana; Martinez Gago, Maria Dolores; Laborda Gonzalez, Belen; Garcia Alonso, Sara; Fernandez Rodriguez, Eloy

    2018-05-22

    Usually serum albumin is measured with dye-binding assay as bromocresol green (BCG) and bromocresol purple (BCP) methods. The aim of this paper was to examine the differences in albumin measurements between the Advia2400 BCG method (AlbBCG), Dimension RxL BCP (AlbBCP) and capillary zone electrophoresis (CZE). Albumin concentrations from 165 serum samples were analysed using AlbBCG, AlbBCP and CZE. CZE was employed to estimate different serum protein fractions. Influence of globulins on albumin concentration discrepancies between methods was estimated as well as the impact of the albumin method on aCa concentrations. Medcalc was employed for statistical analysis, setting a value of P albumin concentrations. AlbBCG were positively biased versus CZE (3.54 g/L). There was good agreement between CZE and ALbBCP (Albumin results from the BCP and BCG methods may result in unacceptable differences and clinical confusion, especially at lower albumin concentrations. Serum acute phase proteins contribute to overestimating the albumin concentration using AlbBCG.

  15. Comparison between IV immune globulin (IVIG) and anti-D globulin for treatment of immune thrombocytopenia: a randomized open-label study.

    Science.gov (United States)

    Eghbali, Aziz; Azadmanesh, Peyman; Bagheri, Bahador; Taherahmadi, Hasan; Sadeghi Sedeh, Bahman

    2016-08-01

    To compare the effect of IV immune globulin (IVIG) and anti-D globulin (anti-D) for treatment of immune thrombocytopenia (ITP) in children. A randomized, open-label, single-center clinical trial was carried out in Amir-Kabir Hospital (Arak, Iran). The study was performed on 60 children with acute and chronic ITP, aged from 1 to 15 years. Patients were randomly assigned (1:1) to 50 μg/kg anti-D or 1 g/kg IVIG. Platelet counting was performed at baseline and at 3, 7, and 14 days after treatment termination. Safety assessment was performed in all patients. Anti-D caused a quicker response on the 3rd day of treatment (P anti-D had lower rate of side effects including fever (P anti-D was associated with rapid rise of platelets compared to IVIG. In addition, anti-D treatment had acceptable safety profile. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  16. U.S. vaccine and immune globulin product shortages, 2001-15.

    Science.gov (United States)

    Ziesenitz, Victoria C; Mazer-Amirshahi, Maryann; Zocchi, Mark S; Fox, Erin R; May, Larissa S

    2017-11-15

    Trends in shortages of vaccines and immune globulin products from 2001 through 2015 in the United States are described. Drug shortage data from January 2001 through December 2015 were obtained from the University of Utah Drug Information Service. Shortage data for vaccines and immune globulins were analyzed, focusing on the type of product, reason for shortage, shortage duration, shortages requiring vaccine deferral, and whether the drug was a single-source product. Inclusion of the product into the pediatric vaccination schedule was also noted. Of the 2,080 reported drug shortages, 59 (2.8%) were for vaccines and immune globulin products. Of those, 2 shortages (3%) remained active at the end of the study period. The median shortage duration was 16.8 months. The most common products on shortage were viral vaccines (58%), especially hepatitis A, hepatitis B, rabies, and varicella vaccines (4 shortages each). A vaccine deferral was required for 21 shortages (36%), and single-source products were on shortage 30 times (51%). The most common reason for shortage was manufacturing problems (51%), followed by supply-and-demand issues (7%). Thirty shortages (51%) were for products on the pediatric schedule, with a median duration of 21.7 months. Drug shortages of vaccines and immune globulin products accounted for only 2.8% of reported drug shortages within a 15-year period, but about half of these shortages involved products on the pediatric vaccination schedule, which may have significant public health implications. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  17. Relationship between Post-kidney Transplantation Antithymocyte Globulin Therapy and Wound Healing Complications

    OpenAIRE

    Pourmand, G. R.; Dehghani, S.; Saraji, A.; Khaki, S.; Mortazavi, S. H.; Mehrsai, A.; Sajadi, H.

    2012-01-01

    Background: Wound healing disorders are probably the most common post-transplantation surgical complications. It is thought that wound healing disturbance occurs due to antiproliferative effects of immunosuppressive drugs. On the other hand, success of transplantation is dependent on immunosuppressive therapies. Antihuman thymocyte globulin (ATG) has been widely used as induction therapy but the impact of this treatment on wound healing is not fully understood. Objective: To investigate wound...

  18. Influence of immunization on serum γ-globulin levels of calves following whole-body X irradiation

    International Nuclear Information System (INIS)

    Koch, F.; Mehlhorn, G.; Neumeister, K.; Johannsen, U.; Panndorf, H.

    1980-01-01

    Calves aged 2.5 to 4 months were whole-body X irradiated with mean lethal doses between 1.2 and 1.7 Gy. The effect of different immunization procedures on the irradiation-induced reaction of the serum gamma globulin levels was studied. Immunization 14 and 21 days before irradiation resulted in obvious stimulation gamma globulin production. After parenteral antigen administration the nearly 2 weeks lasting increase of the gamma globulin level rose in the irradiated animals but declined in the sham-irradiated calves. After a lethal dosis of 1.7 Gy there was a decrease of the gamma globulins 3 weeks post irradiation, at the climax of the radiation syndrome. When 1.5 Gy were used the increase of the gamma globulin concentration was observed also after oral administration of the antigen. The response of the irradiated animals in the secondary reaction of the antibody production was most lear after boosting with homologous bacteria. The stimulating effect of the irradiation on the serum globulin levels after immunization prior to irradiation has been attributed to the reaction of the immunoglobulin-producing system to the release of tissue proteins and antigens, respectively

  19. Interaction of Soybean 7S Globulin Peptide with Cell Membrane Model via Isothermal Titration Calorimetry, Quartz Crystal Microbalance with Dissipation, and Langmuir Monolayer Study.

    Science.gov (United States)

    Zou, Yuan; Pan, Runting; Ruan, Qijun; Wan, Zhili; Guo, Jian; Yang, Xiaoquan

    2018-05-16

    To understand the underlying molecular mechanism of the cholesterol-lowering effect of soybean 7S globulins, the interactions of their pepsin-released peptides (7S-peptides) with cell membrane models consisting of dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), and cholesterol (CHOL) were systematically studied. The results showed that 7S-peptides were bound to DPPC/DOPC/CHOL liposomes mainly through van der Waals forces and hydrogen bonds, and the presence of higher CHOL concentrations enhanced the binding affinity (e.g., DPPC/DOPC/CHOL = 1:1:0, binding ratio = 0.114; DPPC/DOPC/CHOL = 1:1:1, binding ratio = 2.02). Compression isotherms indicated that the incorporation of 7S-peptides increased the DPPC/DOPC/CHOL monolayer fluidity and the lipid raft size. The presence of CHOL accelerated the 7S-peptide accumulation on lipid rafts, which could serve as platforms for peptides to develop into β-sheet rich structures. These results allow us to hypothesize that 7S-peptides may indirectly influence membrane protein functions via altering the membrane organization in the enterocytes.

  20. Detection of a novel specificity (CTLA-4) in ATG/TMG globulins and sera from ATG-treated leukemic patients.

    Science.gov (United States)

    Pistillo, Maria Pia; Tazzari, Pier Luigi; Bonifazi, Francesca; Bandini, Giuseppe; Kato, Tomohiro; Matsui, Toshihiro; Nishioka, Kusuki; Conte, Roberto; Ferrara, Giovanni Battista

    2002-04-27

    T-cell costimulation has been shown to provide positive signals for T-cell activation and generation of effector activity. In this study, we analyzed the presence of antibodies (Abs) against the T-lymphocyte costimulatory molecules CD28, CTLA-4, CD80, and CD86 in anti-T-lymphocyte (ATG) and antithymocyte (TMG) globulin preparations to address their mechanism of action. We focused our attention on the role of CTLA-4-specific Abs in the immunosuppressive effect of ATG/TMG, because anti-CTLA-4 agonistic Abs may suppress T-cell proliferation and nonagonistic Abs may lead to T-cell depletion through an Ab-dependent cell cytotoxicity mechanism. ATG/TMG and patients' sera were tested for binding to recombinant human costimulatory molecules by ELISA techniques. CTLA-4 specificity was also analyzed by cytoplasmic immunofluorescence staining of a CTLA-4 transfectant by competitive inhibition immunofluorescence and by cell proliferation assay in allogeneic mixed lymphocyte reaction (MLR). Either ATG or TMG predominantly contained anti-CTLA-4 Abs, with higher reactivity in ATG followed by anti-CD86 and -CD28 Abs, whereas anti-CD80 Abs were found only in ATG. Anti-CTLA-4 Abs present in ATG/TMG recognized the native form of CTLA-4 molecule, and their removal reduced the effect of ATG in an allogeneic MLR. Kinetic studies indicated that such Abs were present in the sera of 12 ATG-treated leukemic patients up to 21 days after ATG administration. These data suggest that the novel anti-CTLA-4 Abs found in ATG may greatly contribute to its immunosuppressive effect, thus accounting for the absence of rejection and exceptionally low incidence of graft-versus-host disease in the group of patients analyzed.

  1. Binding of rare earths to serum proteins and DNA

    International Nuclear Information System (INIS)

    Rosoff, B.; Spencer, H.

    1979-01-01

    In order to investigate further the physiological behavior of rare earths and rare earth chelates, studies of the binding of 46 Sc, 91 Y, and 140 La to serum proteins and to nucleic acids were performed using the methods of equilibrium dialysis and ultrafiltration. The binding of lanthanum and yttrium as the chlorides to α-globulin increased as the free rare earth concentration increased. When scandium and lanthanum were chelated in nitrilotriacetate (NTA) the binding to α-globulin was considerably less and there was no binding to albumin. The binding of 46 Sc chelated to ethylenediamine di(O-hydroxyphenylacetate) (EDDHA) was five times greater than of 46 Sc chloride. When the free scandium concentration was increased, the moles bound per mole of protein increased proportionally and the binding was reversible. Scandium was 100% filterable from a mixture of human serum and from the scandium chelates with high stability constants scandium diethylenetriaminepentaacetate (ScDTPA), scandium ethylenediaminetetraacetate (ScEDTA) and scandium cyclohexane trans-1,2-diaminetetraacetate (ScCDTA) respectively. In contrast, only 2% of the scandium was filterable when scandium nitrilotriacetate, a scandium chelate of low stability constant, was used. (Auth.)

  2. Electrophoretic Profile of Albumin, α1, α2, β and γ Globulin in Sera of Opioid Dependants and Non-dependants

    Directory of Open Access Journals (Sweden)

    koros Div-salaar

    2008-02-01

    Full Text Available Div-salaar K1, Saravani R2, Shamsi-e-meimandi M3, Taei M4, Sheikholeslami A5 1. MSc. Staff member of Neurology Sciences Research Center, Kerman University of Medical Sciences 2. Instructor, Department of Biochemistry, Faculty of Medicine, Zahedan University of Medical Sciences 3. Instructor, Department of Physiology and Pharmacology, Faculty of Medicine, Neurology Sciences Research Center, Karman University of Medical Sciences 4. Researcher, Neurology Sciences Research Center, Karman University of Medical Sciences 5. B.Sc in Environmental Hygiene, Kerman University of Medical Sciences Abstract Background: The prevalence rate of opioids consumption is high in Iran. The latest research approach related to substance abuse considers the role of plasma proteins in novel treatments of addiction. Since long-term consumption of opioids has some effects on liver function and plasma transfer systems, the present study was designed to determine the electrophoretic profile of plasma proteins in opiates-addict subjects. Materials and methods: In this cross-control study, the sample groups consisted of 42 opium consumers and 35 heroine dependents as case group and 35 non-addict volunteers as control group. The control group was matched with addicts for age and sex. Opioid consumption was confirmed by laboratory diagnostic tests on urine samples such as immunochromatography (RSA, rapidosis and complementary tests including liquid-solid column chromatography and thin layer chromatography (TLC. After blood collection and serum preparation, serum electrophoresis was performed. Data were presented as mean±SEM and analyzed by SPSS ver.11.5. The comparison of groups was done by using parametric tests and p<0.01 was considered as statistically significant. Results: There was no significant difference in the amounts of albumin, alpha-1-globulin, alpha-2-globulin and beta-globulin between groups. Gamma-globulin concentration was not significantly different between

  3. 11S Storage globulin from pumpkin seeds: regularities of proteolysis by papain.

    Science.gov (United States)

    Rudakova, A S; Rudakov, S V; Kakhovskaya, I A; Shutov, A D

    2014-08-01

    Limited proteolysis of the α- and β-chains and deep cleavage of the αβ-subunits by the cooperative (one-by-one) mechanism was observed in the course of papain hydrolysis of cucurbitin, an 11S storage globulin from seeds of the pumpkin Cucurbita maxima. An independent analysis of the kinetics of the limited and cooperative proteolyses revealed that the reaction occurs in two successive steps. In the first step, limited proteolysis consisting of detachments of short terminal peptides from the α- and β-chains was observed. The cooperative proteolysis, which occurs as a pseudo-first order reaction, started at the second step. Therefore, the limited proteolysis at the first step plays a regulatory role, impacting the rate of deep degradation of cucurbitin molecules by the cooperative mechanism. Structural alterations of cucurbitin induced by limited proteolysis are suggested to generate its susceptibility to cooperative proteolysis. These alterations are tentatively discussed on the basis of the tertiary structure of the cucurbitin subunit pdb|2EVX in comparison with previously obtained data on features of degradation of soybean 11S globulin hydrolyzed by papain.

  4. Outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine A

    Directory of Open Access Journals (Sweden)

    Marlene Pereira Garanito

    2014-09-01

    Full Text Available Objective: To evaluate the outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine as first-line treatment at this institution. Methods: Retrospective analysis of 26 pediatric patients with aplastic anemia, treated between 1996 and 2011 with rabbit antithymocyte globulin plus cyclosporine. Results: The overall response rate at six months was 34.6% (9/26, and the cumulative incidence of relapse was 26.5% (95% confidence interval [CI]: 1.4%-66% at 5 years. The cumulative incidence of clonal evolution after immunosuppressive therapy was 8.3% (95% CI: 0.001%-53.7% at five years with both clonal evolutions in non -responders who acquired monosomy 7 karyotype. The overall survival at five years was 73.6% (95% CI: 49.2%-87.5%. Conclusions: The present results confirm the poor response rate with rabbit antithymocyte globulin as first therapy in pediatrics patients, similar to what has been reported for patients of all ages. This confirmation is problematic in Brazil, given the lack of horse antithymocyte globulin in many markets outside the United States. Resumo: Objetivo: Avaliar o resultado de crianças com anemia aplástica grave adquirida tratadas com globulina antitimocítica de coelho e ciclosporina como tratamento inicial em nosso instituto. Métodos: Análise retrospectiva de 26 pacientes pediátricos com anemia aplástica tratados entre 1996 e 2011 com globulina antitimocítica de coelho e ciclosporina. Resultados: A taxa de resposta geral em seis meses foi de 34,6% (9/26, e a incidência acumulada de recorrência foi de 26,5% (intervalo de confiança [IC] de 95%,1,4%-66% em cinco anos. A incidência acumulada de evolução clonal após a terapia imunossupressora foi de 8,3% (IC 95%, 0,001%-53,7% em cinco anos, com ambas as evoluções clonais em pacientes sem resposta que adquiriram o cariótipo com monossomia 7. A sobrevida geral em cinco anos foi de 73,6% (IC 95%, 49

  5. Thyroid hormones and thyroxine-binding globulin in relation to liver function and serum testosterone in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Becker, U; Gluud, C; Bennett, Patrick

    1988-01-01

    concentrations of triiodothyronine (T3) decreased significantly (p less than 0.05) and thyroid-stimulating hormone (TSH) increased with progressing liver dysfunction. Serum concentrations of tetraiodothyronine (T4), TBG and T4/TBG ratio did not correlate significantly with liver function. Serum T3 concentrations...

  6. 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, ...

  7. 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

    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 signi......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...... 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...

  8. Disturbance of binding of corticosteroids with blood plasma proteins during acute radiation sickness of different experimental animals

    International Nuclear Information System (INIS)

    Moroz, B.B.; Omel'chuk, N.N.

    1979-01-01

    In experiments on different animals a study was made of the effect of total-body γ-irradiation on binding of corticosteroids with blood plasma proteins. It was demonstrated that the increase in the number of physiologically active corticosteroids at the peak of radiation sickness is due to diminution of linking ability of corticosteroid-binding globulin of blood plasma and independent ot the total concentration of hormones in blood which is, evidently, a general radiobiological law

  9. Identification and characterization of riboflavin-binding proteins in human circulation

    International Nuclear Information System (INIS)

    Innis-Whitehouse, W.S.A.

    1988-01-01

    Riboflavin binding by plasma proteins from healthy human subjects was examined by equilibrium dialysis and binding was observed to vary over a greater than 10-fold range. Upon fractionation of plasma by gel filtration, the major riboflavin-binding components eluted with albumin and gamma-globulins. Albumin was purified and found to bind riboflavin only very weakly, although FMN and photo-chemical degradation products were more tightly bound. Most of the binding occurred in the gamma-globulin fraction and was attributed to immunoglobulins because the binding proteins and immunoglobulins copurified using various methods, were removed by treatment of plasma with protein A-agarose, and were coincident upon immuno-electrophoresis followed by autoradiography to detect [2- 14 C]-riboflavin. Binding differences among plasma samples were reflected in the binding recovered with the immunoglobulin fractions; however, there was not a direct relationship between the amount of immunoglobulin and the amount of [2- 14 C]riboflavin bound. Hence, it appeared that the binding was due to a subfraction of immunoglobulins

  10. 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.

  11. PROPHYLACTIC ADMINISTRATION OF RESPIRATORY SYNCYTIAL VIRUS IMMUNE GLOBULIN TO HIGH-RISK INFANTS AND YOUNG-CHILDREN

    NARCIS (Netherlands)

    GROOTHUIS, [No Value; SIMOES, EAF; LEVIN, MJ; HALL, CB; LONG, CE; RODRIGUEZ, WJ; ARROBIO, J; MEISSNER, HC; FULTON, DR; WELLIVER, RC; TRISTRAM, DA; SIBER, GR; PRINCE, GA; VANRADEN, M; HEMMING, VG

    1993-01-01

    Background. Infants with cardiac disease or prematurity are at risk for severe illness caused by respiratory syncytial virus. Immune globulin with a high titer of antibodies against respiratory syncytial virus may offer infants and young children at risk protection from this serious, common

  12. 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.…

  13. Rapid changes in the serum total protein and globulin levels in complications caused by facultatively pathogenic Gram-negative bacteria.

    Science.gov (United States)

    Petrás, G; Kiss, S; Juraszek, J; Merétey, K

    1978-01-01

    The changes in the levels of total protein and four globulin fractions were followed up throughout the entire course of complications caused by Gram-negative facultative pathogens in 37 acute cases of respiratory insufficiency accompanying different underlying illnesses and in 9 chronic, bedridden patients given artificial ventilation. At the onset of the infectious complications, in the first place in septic shock, the levels of various globulin fractions showed a decrease corresponding to a half-life of 2 to 4 days. Neither the increased catabolism, nor the protein losses by the urine and tracheal secretions offer a sufficient explanation for the escape of globulins of this extent from the plasma. It seems that this is a consequence of the increase in capillary permeability due to the effect of antigen-antibody reactions and that of endotoxin. As a result, in the critical phase of the infectious complications, at the point of culmination, e.g. in septic shock, diminished amount of different globulins is transported to the site of utilization, that is, to the inflammatory area.

  14. Preparation of anti-CEA and anti-goat γ-globulin sera for radioimmunologic assay of carcinoembryonic antigen

    International Nuclear Information System (INIS)

    Kusnierczyk-Glazman, H.; Breborowicz, J.

    1977-01-01

    Goats were immunized with purified carcinoembryonic antigen, and the suitability of the antisera for clinical assays of carcinoembryonic antigen was characterized. Reactivity of equine sera to goat γ-globulin as a precipitating factor in the radioimmunologic double antibody technique was also evaluated. (author)

  15. 6-methylprednisolone does not impair anti-thymocyte globulin (ATG) immunosuppressive activity in non-human primates

    NARCIS (Netherlands)

    Preville, [No Value; Sick, E; Beauchard, S; Ossevoort, M; Tiollier, J; Revillard, JP; Jonker, Margreet

    2001-01-01

    Background: Induction treatments with anti-thymocyte globulin (ATG) in solid organ transplantation may enhance the efficacy of maintenance immunosuppressive therapy. Since ATG can trigger Fas (CD95) mediated T cell apoptosis, a process antagonized in vitro by corticosteroids, an important issue is

  16. 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....

  17. 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...

  18. 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...

  19. Prognostic value of pretreatment albumin/globulin ratio in digestive system cancers: A meta-analysis.

    Science.gov (United States)

    Guo, Hui-Wen; Yuan, Tang-Zhan; Chen, Jia-Xi; Zheng, Yang

    2018-01-01

    The albumin/globulin ratio (AGR) has been widely reported to be a potential predictor of prognosis in digestive system cancers (DSCs), but convincing conclusions have not been made. Therefore, herein, we performed a meta-analysis of relevant studies regarding this topic to evaluate the prognostic value of AGR in patients with DSCs. Three databases, including PubMed, EMBase, and Web of science, were searched comprehensively for eligible studies through September 8, 2017. The outcomes of interest included overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). In our meta-analysis, pooled analysis of 13 studies with 9269 patients showed that a low AGR was significantly correlated with poor OS (HR = 1.94; 95% CI: 1.57-2.38; P digestive system cancers. A low pretreatment AGR may be a useful predictive prognostic biomarker in human digestive system cancers.

  20. 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

  1. 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, pseed size, tofu hardness and water holding capacity and led to significant changes to the profile of storage protein 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. 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.

  3. 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.

  4. 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.

  5. Heat-Induced Soluble Protein Aggregates from Mixed Pea Globulins and β-Lactoglobulin.

    Science.gov (United States)

    Chihi, Mohamed-Lazhar; Mession, Jean-luc; Sok, Nicolas; Saurel, Rémi

    2016-04-06

    The present work investigates the formation of protein aggregates (85 °C, 60 min incubation) upon heat treatment of β-lactoglobulin (βlg)-pea globulins (Glob) mixtures at pH 7.2 and 5 mM NaCl from laboratory-prepared protein isolates. Various βlg/Glob weight ratios were applied, for a total protein concentration of 2 wt % in admixture. Different analytical methods were used to determine the aggregation behavior of "mixed" aggregates, that is, surface hydrophobicity and also sulfhydryl content, protein interactions by means of SDS-PAGE electrophoresis, and molecule size distribution by DLS and gel filtration. The production of "mixed" thermal aggregates would involve both the formation of new disulfide bonds and noncovalent interactions between the denatured βlg and Glob subunits. The majority of "mixed" soluble aggregates displayed higher molecular weight and smaller diameter than those for Glob heated in isolation. The development of pea-whey protein "mixed" aggregates may help to design new ingredients for the control of innovative food textures.

  6. Immune reconstitution with two different rabbit polyclonal anti-thymocytes globulins.

    Science.gov (United States)

    Bamoulid, Jamal; Crepin, Thomas; Gaiffe, Emilie; Laheurte, Caroline; Moulin, Bruno; Frimat, Luc; Rieu, Philippe; Mousson, Christiane; Durrbach, Antoine; Heng, Anne-Elisabeth; Rebibou, Jean-Michel; Saas, Philippe; Courivaud, Cécile; Ducloux, Didier

    2017-12-01

    Broad T cell depletion by polyclonal anti-thymocyte globulins (ATG) has been used for many years as a part of immunosuppressive treatment in transplantation. Currently, two different ATG are used in clinical practice, Thymoglobulin and Grafalon. Due to differences in the immunization source, these products contain different specificities and quantity of antibodies. These differences may have clinical consequences. We conducted a nested study in a large prospective multicentric cohort of kidney transplant to determine whether Grafalon-treated and Thymoglobulin-treated patients experience different lymphocyte reconstitution and clinical outcomes. 182 patients matched for age, gender, CMV status, CMV prophylaxis, number of previous transplantation, and maintenance immunosuppressive treatment were included (Thymoglobulin, [n=91]; Grafalon®, [n=91]). One-year post-transplant, recent thymic emigrants were significantly decreased (12±10% vs 21±12%; p<0.001) in Grafalon-treated patients. By contrast, T cell activation (CD38+DR+Ki67+) and senescence (CD8+CD57+CD28-) was increased in Thymoglobulin-treated patients. Compared to Grafalon, Thymoglobulin was not associated with a significantly different rate of acute rejection. CMV disease (p=0.013) was more frequent in Thymoglobulin-treated patients. Grafalon and Thymoglobulin seem to be equivalent to prevent acute rejection. CMV disease is more frequent in Thymoglobulin-treated patients. One year post-transplant immune profile profoundly differs according to the type of ATG. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Clinical Significance of Preoperative Albumin and Globulin Ratio in Patients with Gastric Cancer Undergoing Treatment

    Directory of Open Access Journals (Sweden)

    Min-jie Mao

    2017-01-01

    Full Text Available Background. The pretreatment albumin and globulin ratio (AGR was an inflammation-associated factor which was related to the overall survival in various malignancies. The aim of this study was to evaluate the prognostic value of AGR in patients with gastric cancer. Method. This retrospective study included 862 cases pathologically diagnosed with gastric cancer. All patients were randomly divided into the testing group (431 cases and validation group (431 cases. The relationships of AGR with clinicopathologic characteristics and prognosis were analyzed by Kaplan-Meier and Cox regression methods. Results. In the testing group, the median overall survival was 26.90 months and the cutoff value of AGR was 1.50 based on R language. Kaplan-Meier analysis showed that lower AGR was correlated with poorer overall survival. Multivariate analysis demonstrated that AGR was an independent prognostic factor for overall survival (HR: 0.584, 95% CI = 0.351–0.973, and p = 0.039. In the validation group, the median overall survival was 24.10 months. Lower AGR (≤1.50 also had a significantly poorer overall survival by Kaplan-Meier analysis. According to multivariate analysis, the AGR was also confirmed to be an independent prognostic factor for overall survival (HR: 0.578, 95% CI = 0.373–0.897, and p = 0.015. Conclusions. Our study suggested that the pretreatment AGR could be a prognostic biomarker for overall survival in patients with gastric cancer.

  8. Rabbit antithymocyte globulin is more beneficial in standard kidney than in extended donor recipients.

    Science.gov (United States)

    Hardinger, Karen L; Brennan, Daniel C; Schnitzler, Mark A

    2009-05-15

    In a randomized, international study comparing rabbit antithymocyte globulin (TMG) and basiliximab (BAS) induction in renal transplant recipients at risk for delayed graft function or acute rejection (n=278), TMG was associated with less acute rejection at 1 year. This study analyzed outcomes stratified by standard criteria donor (SCD), extended criteria donor (ECD), and hypertensive donor. Data-capture limitations necessitated defining ECD as donor age more than 60 years or 50 to 60 years with hypertension and renal insufficiency. Seventy-five recipients received ECD-kidneys (28.4% TMG vs. 25.6% BAS, P=NS) and 203 recipients received SCD-kidneys (72.6% TMG vs. 74.4% BAS, P=NS). Recipients of an ECD or hypertensive donor-kidney had similar outcomes between treatment groups. Recipients of an SCD-kidney treated with TMG had less rejection (odds ratio [OR] 0.48). Recipients of a normotensive donor-kidney treated with TMG had less rejection (OR 0.56). Recipients of a normotensive, SCD-kidney treated with TMG had less rejection (OR 0.47) and death (OR 0.17) than their counterparts treated with BAS. Contrary to its perceived niche in recipients of ECD-kidneys, TMG was most beneficial in patients who received a normotensive, deceased SCD kidney.

  9. [Value of the albumin to globulin ratio in predicting severity and prognosis in myasthenia gravis patients].

    Science.gov (United States)

    Yang, D H; Su, Z Q; Chen, Y; Chen, Z B; Ding, Z N; Weng, Y Y; Li, J; Li, X; Tong, Q L; Han, Y X; Zhang, X

    2016-03-08

    To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients. A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR 1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization. The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (Pmyasthenia gravis. At the multivariate Cox regression analysis, the AGR (Pmyasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (Pmyasthenia crisis. The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.

  10. Clinical experience with thymoglobulin and antithymocyte globulin-Fresenius as induction therapy in renal transplant patients: a retrospective study.

    Science.gov (United States)

    Cicora, Federico; Mos, Fernando; Paz, Marta; Roberti, Javier

    2013-10-01

    We describe our experiences with, and compare the outcomes of, 2 groups of renal transplant patients treated with thymoglobulin or antithymocyte globulin-Fresenius as induction therapy at transplant to reduce the incidence of acute rejection and prevent delayed allograft function. Twenty-four recipients of deceased-donor or living-donor kidney transplants received thymoglobulin, and 23 patients received antithymocyte globulin-Fresenius. Patient and graft survival and efficacy and safety were assessed at 3 months. The demographic characteristics of both groups were comparable, but the predominant donor type was significantly different. Incidence of complications, delayed graft function, and creatinine concentrations were comparable in both groups. At 3 months after the transplant, patient survival rate was 92% in the thymoglobulin group and 96% in the antithymocyte globulin-Fresenius group (P > .05), and death-censored graft survival rate for both groups was not significantly different. Average hematocrit and lymphocyte, neutrophil, and platelet counts were comparable in both groups at 3 months' follow-up. Average white blood count at 1 month was significantly different between the groups: at 5.62 ± 2.45 × 103 cells/mm³ in the thymoglobulin group and 7.85 ± 4.10 × 103 cells/mm³ in the ATG-F group (P Fresenius were generally comparable.

  11. 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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

    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- + 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

  13. Variations in riboflavin binding by human plasma: identification of immunoglobulins as the major proteins responsible

    International Nuclear Information System (INIS)

    Innis, W.S.; McCormick, D.B.; Merrill, A.H. Jr.

    1985-01-01

    Riboflavin binding by plasma proteins from healthy human subjects was examined by equilibrium dialysis using a physiological concentration of [2-14C]riboflavin (0.04 microM). Binding ranged from 0.080 to 0.917 pmole of riboflavin/mg of protein (with a mean +/- SD of 0.274 +/- 0.206), which corresponded to 4.14 to 49.4 pmole/ml of plasma (15.5 +/- 11.0) (N = 34). Males and females yielded similar results. Upon fractionation of plasma by gel filtration, the major riboflavin-binding components eluted with albumin and gamma-globulins. Albumin was purified and found to bind riboflavin only very weakly (Kd = 3.8 to 10.4 mM), although FMN and photochemical degradation products (e.g., lumiflavine and lumichrome) were more tightly bound. Binding in the gamma-globulin fraction was attributed to IgG and IGA because the binding protein(s) and immunoglobulins copurified using various methods were removed by treatment of plasma with protein A-agarose, and were coincident upon immunoelectrophoresis followed by autoradiography to detect [2-14C]riboflavin. Differences among the plasma samples correlated with the binding recovered with the immunoglobulins. Binding was not directly related to the total IgG or IgA levels of subjects. Hence, it appears that the binding is due to a subfraction of these proteins. These findings suggest that riboflavin-binding immunoglobulins are a major cause of variations in riboflavin binding in human circulation, and may therefore affect the utilization of this micronutrient

  14. 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.

  15. A successful desensitization protocol for horse-derived antithymocyte globulin in severe aplastic anemia.

    Science.gov (United States)

    Demir, Esen; Cigerci Günaydın, Nurşen; Karadaş, Nihal; Gülen, Figen; Tanac, Remziye; Yılmaz, Deniz

    2015-03-01

    Horse antithymocyte globulin (h-ATG) (ATGAM(®) ) is the first choice of treatment in very severe patients with aplastic anemia who do not have any HLA matched sibling donor. h-ATG is a heterologous serum that may cause anaphylaxis. Alternative treatment strategies must be planned in case of hypersensitivity. Desensitization must be considered in patients without an alternative treatment of choice. We aimed to present the h-ATG desensitization protocol and consider its effectiveness in patients with aplastic anemia who are hypersensitized with h-ATG and do not have an alternative treatment of choice. Skin prick tests were performed with non-diluted solution in eight very severe patients with aplastic anemia who are followed up in Ege University Children's Hospital. Although skin prick test was found negative in these eight patients, different dilution h-ATG intradermal tests were performed and found positive in all patients. h-ATG desensitization program was started to these hypersensitized patients. Desensitization program was started to six male and two female very severe patients with aplastic anemia whose ages were between seven and 19 yr (median: 12.9 yr). All of the patients completed the desensitization program. While local reaction was seen in two patients, systemic reaction was seen in one patient and late reaction was seen in one patient during and after desensitization program. A successful desensitization program with h-ATG in children with aplastic anemia is presented. Even though there is not an exposure before to such high allergy potential heterologous serum, skin tests should be performed and desensitization must be started to patients who are hypersensitized to h-ATG. As the expected effectiveness of the treatment is so much, the desensitization protocol can be carried out safely and effectively with trained stuff although allergic reactions can be seen. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. 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.

  17. 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.

  18. Serum testosterone levels in males are not associated with entrepreneurial behavior in two independent observational studies.

    Science.gov (United States)

    van der Loos, Matthijs J H M; Haring, Robin; Rietveld, Cornelius A; Baumeister, Sebastian E; Groenen, Patrick J F; Hofman, Albert; de Jong, Frank H; Koellinger, Philipp D; Kohlmann, Thomas; Nauck, Matthias A; Rivadeneira, Fernando; Uitterlinden, André G; van Rooij, Frank J A; Wallaschofski, Henri; Thurik, A Roy

    2013-07-02

    Previous research has suggested a positive association between testosterone (T) and entrepreneurial behavior in males. However, this evidence was found in a study with a small sample size and has not been replicated. In the present study, we aimed to verify this association using two large, independent, population-based samples of males. We tested the association of T with entrepreneurial behavior, operationalized as self-employment, using data from the Rotterdam Study (N=587) and the Study of Health in Pomerania (N=1697). Total testosterone (TT) and sex hormone-binding globulin (SHBG) were measured in the serum. Free testosterone (FT), non-SHBG-bound T (non-SHBG-T), and the TT/SHBG ratio were calculated and used as measures of bioactive serum T, in addition to TT adjusted for SHBG. Using logistic regression models, we found no significant associations between any of the serum T measures and self-employment in either of the samples. To our knowledge, this is the first large-scale study on the relationship between serum T and entrepreneurial behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Use of the Vettest 8008 and refractometry for determination of total protein, albumin, and globulin concentrations in feline effusions.

    Science.gov (United States)

    Papasouliotis, Kostas; Murphy, Kate; Dodkin, Steve; Torrance, Andy G

    2002-01-01

    Pleural and peritoneal effusion is a common clinical finding in feline practice. Determination of fluid albumin (ALB) and globulin (GLOB) concentrations in addition to total protein (TP) concentration can be helpful in diagnosing or ruling out certain diseases in cats, especially feline infectious peritonitis (FIP). The objective of this study was to compare effusion TP, ALB, and GLOB results obtained by a refractometer and a bench-top dry chemistry analyzer with those results obtained by a reference method. Twenty-six pleural and 14 peritoneal effusion samples were analyzed from 40 cats with various diseases. TP and ALB concentrations were determined by a reference automated wet chemistry analyzer (Kone Specific, Kone Instruments, Espoo, Finland), a bench-top dry chemistry analyzer (Vettest 8008, IDEXX Laboratories Ltd, Chalfont St Peter, UK), and a refractometer (Atago SPR-T2, Atago Co, Tokyo, Japan). GLOB, albumin to globulin (A/G) ratio, and globulins as a percentage of total proteins (GLOB%) were calculated. Results were analyzed by paired t tests, difference plots, and Deming s regression analysis. Correlation coefficients (r) for TP with Vettest versus Kone and refractometer versus Kone methods were.97 and.94, respectively. GLOB and GLOB% values were significantly higher and A/G ratios were significantly lower with Vettest versus Kone methods. Correlation coefficients for ALB, GLOB, GLOB% and A/G ratio with Vettest versus Kone methods were.86,.93,.82, and.73, respectively. Although correlation with other methods was good, the refractometer underestimated TP concentrations in 3 samples. The refractometer is an acceptable method for determination of TP concentration in feline effusions. The Vettest 8008 also is an acceptable method for the determination of TP and ALB concentrations, however, calculated A/G ratios obtained with the Vettest are unacceptable.

  20. 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.

  1. [Comparison of two types of antithymocyte globulin in the treatment of children with aplastic anemia].

    Science.gov (United States)

    Xie, X T; He, W; Shi, W; Zhou, X X; Qiao, X H

    2016-04-01

    This study was designed to compare the effects of the anti-human T lymphocyte globulin (Fresenius, ATG-F)and rabbit anti-human thymocyte immunoglobulin (Genzyme, R-ATG)in the treatment of childhood aplastic anemia (AA) and their effects. A total of 59 children with aplastic anemia were analyzed in the present study, including 34 cases of severe aplastic anemia (SAA), 12 cases of very severe aplastic anemia (VSAA) and 13 cases of transfusion-dependent non-severe aplastic anemia (NSAA). While receiving immunosuppressive therapy (IST), 30 and 29 patients, with long-term oral supplement with cyclosporin A (CSA), androgen and Chinese traditional medicines, were treated with ATG-F and R-ATG, respectively. When it was necessary, some supportive cares such as component transfusion and infection control were also employed. Absolute counts of peripheral blood lymphocyte (ALC) at various time points were dynamically detected after ATG therapy. According to the International Aplastic Anemia Treatment and Effect standards. There were no statistically significant differences in the overall response rate (67%(20/30)vs. 69%(20/29), χ(2)=0.036, P=0.676) and the survival rate (87%(26/30)vs. 83%(24/29), χ(2)=0.173, P=0.676) between the ATG-F and R-ATG groups. There were significant and long-term ALC decrease after ATG therapy, the rate of ALC decrease in ATG-F and R-ATG group, the ALC only recovered to 47.8% (ATG-F group) and 47.4% (R-ATG group) of the pre-treatment level respectively. ATG-F 5 mg/(kg·d) and R-ATG 3.75 mg/(kg·d)could achieve similar effects in the treatment of childhood AA, through similar significant clearance of T cells. Therefore, all of these suggest that ATG-F and R-ATG might serve as the drugs of front-line choice for IST in childhood AA patients who do not have an available human leukocyte antigen identical related donor.

  2. Associations of lead and cadmium with sex hormones in adult males

    Energy Technology Data Exchange (ETDEWEB)

    Kresovich, Jacob K., E-mail: jkreso2@uic.edu; Argos, Maria; Turyk, Mary E.

    2015-10-15

    Heavy metal exposures are ubiquitous in the environment and their relation to sex hormones is not well understood. This paper investigates the associations between selected heavy metals (lead and cadmium) and sex hormones (testosterone, free testosterone, estradiol, free estradiol) as well as other major molecules in the steroid biosynthesis pathway (androstanedione glucuronide and sex-hormone binding globulin (SHBG)). Blood lead and cadmium were selected as biomarkers of exposure, and tested for associations in males using National Health and Nutritional Examination Survey (NHANES) data from 1999–2004. After adjustment for age, race, body mass index, smoking status, diabetes and alcohol intake, blood lead was positively associated with testosterone and SHBG while blood cadmium was positively associated with SHBG. After controlling for additional heavy metal exposure, the associations between lead and testosterone as well as cadmium and SHBG remained significant. Furthermore, the association between blood lead and testosterone was modified by smoking status (P for interaction=0.011), diabetes (P for interaction=0.021) and blood cadmium (P for interaction=0.029). The association between blood cadmium and SHBG levels was modified by blood lead (P for interaction=0.004). This study is the most comprehensive investigation to date regarding the association between heavy metals and sex hormones in males. - Highlights: • We used a nationally representative dataset (NHANES) and employed sample weighting. • We examined associations between lead and cadmium with sex-hormone levels. • Blood lead level was positively associated with serum testosterone and SHBG levels. • Blood cadmium level was positively associated with SHBG levels, modified by lead. • Diabetes, smoking and cadmium modified lead and testosterone association.

  3. Associations of lead and cadmium with sex hormones in adult males

    International Nuclear Information System (INIS)

    Kresovich, Jacob K.; Argos, Maria; Turyk, Mary E.

    2015-01-01

    Heavy metal exposures are ubiquitous in the environment and their relation to sex hormones is not well understood. This paper investigates the associations between selected heavy metals (lead and cadmium) and sex hormones (testosterone, free testosterone, estradiol, free estradiol) as well as other major molecules in the steroid biosynthesis pathway (androstanedione glucuronide and sex-hormone binding globulin (SHBG)). Blood lead and cadmium were selected as biomarkers of exposure, and tested for associations in males using National Health and Nutritional Examination Survey (NHANES) data from 1999–2004. After adjustment for age, race, body mass index, smoking status, diabetes and alcohol intake, blood lead was positively associated with testosterone and SHBG while blood cadmium was positively associated with SHBG. After controlling for additional heavy metal exposure, the associations between lead and testosterone as well as cadmium and SHBG remained significant. Furthermore, the association between blood lead and testosterone was modified by smoking status (P for interaction=0.011), diabetes (P for interaction=0.021) and blood cadmium (P for interaction=0.029). The association between blood cadmium and SHBG levels was modified by blood lead (P for interaction=0.004). This study is the most comprehensive investigation to date regarding the association between heavy metals and sex hormones in males. - Highlights: • We used a nationally representative dataset (NHANES) and employed sample weighting. • We examined associations between lead and cadmium with sex-hormone levels. • Blood lead level was positively associated with serum testosterone and SHBG levels. • Blood cadmium level was positively associated with SHBG levels, modified by lead. • Diabetes, smoking and cadmium modified lead and testosterone association.

  4. Rebalance between 7S and 11S globulins in soybean seeds of differing protein content and 11SA4.

    Science.gov (United States)

    Yang, A; Yu, X; Zheng, A; James, A T

    2016-11-01

    Protein content and globulin subunit composition of soybean seeds affect the quality of soy foods. In this proteomic study, the protein profile of soybean seeds with high (∼45.5%) or low (∼38.6%) protein content and with or without the glycinin (11S) subunit 11SA4 was examined. 44 unique proteins and their homologues were identified and showed that both protein content and 11SA4 influenced the abundance of a number of proteins. The absence of 11SA4 exerted a greater impact than the protein content, and led to a decreased abundance of glycinin G2/A2B1 and G5/A5A4B3 subunits, which resulted in lower total 11S with a concomitant higher total β-conglycinin (7S). Low protein content was associated with higher glycinin G3/A1aB1b and lower glycinin G4/A5A4B3. Using the proteomic approach, it was demonstrated that 11SA4 deficiency induced compensatory accumulation of 7S globulins and led to a similar total abundance for 7S+11S irrespective of protein content or 11SA4. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Modified immunosuppressive therapy with porcine antilymphocyte globulin plus delayed cyclosporine A in children with severe aplastic anemia.

    Science.gov (United States)

    Cui, Qingya; Sha, Pingping; Chen, Haifei; Shen, Hongshi; Qin, Longmei; Li, Zhengyang; Wu, Tianqin; Wang, Zhaoyue

    2018-01-01

    Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CsA) is the standard treatment for children with severe aplastic anemia (SAA) with no human leukocyte antigen-matched siblings. Due to the unavailability of horse ATG in China, porcine antilymphocyte globulin (p-ALG), which is less expensive and more effective than rabbit ATG, is widely used. We sought to evaluate the efficacy and safety profile of modified IST with p-ALG plus delayed CsA at day 21 in 50 SAA children. Eighteen SAA patients who progressed from nonsevere aplastic anemia (NSAA) were classified as SAA-II; the other 32 patients were classified as SAA-I. Overall response (OR) rates at 3, 6 and 12 months were 56, 64 and 62%, respectively. The 10-year overall survival (OS) rate and disease-free survival (DFS) rate were 80 and 56%. The OR, OS and DFS rates in the SAA-I group were clearly better than those in the SAA-II group. Death rate from infection within 30 days was 4%. Modified IST with p-ALG plus delayed CsA is a reliable and well-tolerated treatment for children with SAA, and reduces early death due to infection. Modified IST is more suitable for children with SAA-I.

  6. Physicochemical changes taking place in bovine globulins under the influence of gamma irradiation studied by thermal analysis

    International Nuclear Information System (INIS)

    Ciesla, K.; Vansant, E.F.

    2006-01-01

    Radiation modification of protein based polymers as well as the development of gamma irradiation techniques as a method of food sterilisation and preservation induces necessity of better recognition of the physicochemical changes occurring in proteins after gamma irradiation. Recently differential scanning calorimetry (DSC) was applied widely in structural studies of proteins. Also thermoanalytical methods (TG, DTG) applied for proteins pyrolysis were also found to be useful in characterisation of proteins structure and the properties of proteins containing tissues. In presented paper, the aforementioned methods were applied for investigation of the gamma irradiation influence on thermal decomposition of gamma and alpha globulins and the results were related to their structural modifications. It has been found, that irradiation influences the course of decomposition of gamma and alpha globulins. Irradiation of solid native proteins result in decreased temperature of decomposition, especially decreased temperature of the last stage. The effects of irradiation performed for water suspensions were clearly more significant. The relatively large differences between decomposition of the irradiated and non-irradiated samples were detected by DSC and thermogravimetry already after irradiation of water suspensions

  7. The effect of yeast β-glucan on the amount of albumin, globulin, urea and total protein of broiler chickens

    Directory of Open Access Journals (Sweden)

    ali kargarirezapour

    2013-08-01

    Full Text Available Glucans derived from yeast cell wall are promising alternatives to antibiotics, as they have been shown to improve growth performance and stimulate the immune system of immature broilers. In this study we evaluated the effect of different levels of yeast beta-glucan (YBG on some blood parametrs of broiler chickens. In a factorial experiment based on completely randomized design (the first factor: YBG levels: 0, 0.04 and 0.08% of basal diet and sex as a second factor 144 day old chicks (72 male and 72 female were selected and allocated to different treatments (three replicates of each treatment. The overall experimental period was 34 days. At the end of study, two birds from each pen were randomly selected as a sample. The level of albumin, globulin, urea and total protein was measured on blood samples. Statistical analysis of the results showed that the YBG had no significant effect on albumin, globulin, urea and total protein level. But the amount of plasma albumin and total protein in female chicks was significantly higher than male chicks (p

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

    Science.gov (United States)

    Patel, Samir J; Kuten, Samantha A; Knight, Richard J; Hong, Dana M; Gaber, A Osama

    2014-01-01

    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.

  9. 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.

  10. Concentration of serum thyroid hormone binding proteins after 131I treatment of hyperthyroidism

    International Nuclear Information System (INIS)

    Harrop, J.S.; Hopton, M.R.; Lazarus, J.H.

    1981-01-01

    Serum concentrations of the thyroid hormone binding proteins, thyroxine binding globulin, prealbumin, and albumin were determined in 30 thyrotoxic patients before and after 131 I treatment. Each patient was placed into one of three groups according to response to treatment. The serum concentration of all three proteins rose significantly in 10 patients who became euthyroid, and a greater increase was seen in 10 patients who developed hypothyroidism. There was no significant change in thyroid hormone binding protein concentrations in 10 subjects who remained hyperthyroid. Changes in the concentration of thyroid hormone binding proteins should be borne in mind when total thyroid hormone concentrations are used to monitor the progress of patients receiving treatment for hyperthyroidism. (author)

  11. International reference reagents: antihuman globulin. An ISBT/ICSH joint working party report. International Society of Blood Transfusion. International Committee for Standardization in Haematology.

    Science.gov (United States)

    Case, J; Ford, D S; Chung, A; Collins, R; Kochman, S; Mazda, T; Overbeeke, M; Perera, R; Sakuldamrongpanich, T; Scott, M; Voak, D; Zupańska, B

    1999-01-01

    An international working party has conducted a study designed to select a suitable reference reagent for antihuman globulin, to replace those first made available in 1987. The chosen preparation contains levels of anti-IgG and anti-C3 (anti-C3c and anti-C3d) potency that are considered suitable to serve for reference when evaluating either polyspecific antihuman globulin reagents or those containing their separate monospecific components. The reference material is available in 2-ml freeze-dried aliquots from seven assigned distribution centres.

  12. Anti-thymocyte globulins in kidney transplantation: focus on current indications and long-term immunological side effects.

    Science.gov (United States)

    Bamoulid, Jamal; Staeck, Oliver; Crépin, Thomas; Halleck, Fabian; Saas, Philippe; Brakemeier, Susanne; Ducloux, Didier; Budde, Klemens

    2017-10-01

    Antithymocyte globulins (ATGs) are part of the immunosuppression arsenal currently used by clinicians to prevent or treat acute rejection in solid organ transplantation. ATG is a mixture of non-specific anti-lymphocyte immunoglobulins targeting not only T cell subsets but also several other immune and non-immune cells, rendering its precise immunoglobulin composition difficult to appreciate or to compare from one preparation to another. Furthermore, several mechanisms of action have been described. Taken together, this probably explains the efficacy and the side effects associated with this drug. Recent data suggest a long-term negative impact on allograft and patient outcomes, pointing out the need to better characterize the potential toxicity and the benefit-risk balance associated to this immunosuppressive therapy within large clinical trials. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  13. Differential representation of albumins and globulins during grain development in durum wheat and its possible functional consequences.

    Science.gov (United States)

    Arena, Simona; D'Ambrosio, Chiara; Vitale, Monica; Mazzeo, Fiorella; Mamone, Gianfranco; Di Stasio, Luigia; Maccaferri, Marco; Curci, Pasquale Luca; Sonnante, Gabriella; Zambrano, Nicola; Scaloni, Andrea

    2017-06-06

    Durum wheat (Triticum turgidum ssp. durum (Desf.) Husn.) is an economically important crop used for the production of semolina, which is the basis of pasta and other food products. Its grains provide proteins and starch for human consumption. Grain development is a key process in wheat physiology; it is highly affected by a number of enzymes that control the metabolic processes governing accumulation of starch and storage proteins and ultimately grain weight. Most of these enzymes are present in the albumin/globulin grain fraction, which represents about a quarter of total seed proteins. With the aim to describe the dynamic profile of the albumin/globulin fraction during durum wheat grain development, we performed a proteomic analysis of this subproteome using a two-dimensional differential gel electrophoresis (2D-DIGE)-based approach and compared six developmental stages. A total of 285 differentially (237 over- and 48 under-) represented spots was identified by nanoLC-ESI-LIT-MS/MS, which were associated with 217 non-redundant Triticum sequence entries. Quantitative protein dynamics demonstrated that carbon metabolism, energy, protein destination/storage, disease/defense and cell growth/division functional categories were highly affected during grain development, concomitantly with progressive grain size increase and starch/protein reserve accumulation. Bioinformatic interaction prediction revealed a complex network of differentially represented proteins mainly centered at enzymes involved in carbon and protein metabolism. A description of 18 proteins associated with wheat flour human allergies was also obtained; these components showed augmented levels at the last developmental stages. By providing a comprehensive understanding of the molecular basis of durum wheat grain development, yield and quality formation, this study provides the foundation and reveals potential biomarkers for further investigations of durum wheat breeding and semolina quality. A 2D

  14. Detection of immune complexes in sera of dogs with rheumatic and neoplastic diseases by 125I-Clq binding test

    International Nuclear Information System (INIS)

    Terman, D.S.; Moore, D.; Collins, J.; Johnston, B.; Person, D.; Templeton, J.; Poser, R.; Quinby, F.

    1979-01-01

    Some canine rheumatic and neoplastic diseases bear a striking clinical and serological resemblance to their counterparts in man. In the present study, human 125 I-Clq was employed in a radioimmunoassay for detection of immune complexes in sera of normal dogs and those with rheumatic and neoplastic diseases. Human 125 I-Clq showed binding of 16.7 +- 5.73% in a group of normal dog sera with binding of 32.5 +- 17.3% and 43.0 +- 16.0% in sera of dogs with rheumatic and neoplastic diseases. respectively. Human 125 I-Clq bound similar quantities of heat-aggregated canine and human gamma-globulin over a broad range of concentrations and human 125 I-Clq binding in canine sera was effectively inhibited by similar quantities of heat aggregated canine and human gamma-globulin. Seven of 12 dogs with elevated levels of Clq binding had active clinical and serological rheumatic disease (SLE or rheumatoid arthritis), while none of 7 dogs with values within the normal range had active clinical disease. All 5 dogs with widespread osteogenic sarcoma and all 4 dogs with high grade adenocarcinoma of the mammary gland had elevated Clq binding values while 2 animals with low grade malignancies without evident metastases did not. Thus, it appears that human 125 I-Clq may be employed to assay immune complexes in canine sera and may be a valuable technique for the study of dogs with various rheumatic and neoplastic diseases. (author)

  15. 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.

  16. d-Limonene-induced male rat-specific nephrotoxicity: Evaluation of the association between d-limonene and alpha 2u-globulin

    International Nuclear Information System (INIS)

    Lehman-McKeeman, L.D.; Rodriguez, P.A.; Takigiku, R.; Caudill, D.; Fey, M.L.

    1989-01-01

    d-Limonene is a naturally occurring monoterpene, which when dosed orally, causes a male rat-specific nephrotoxicity manifested acutely as the exacerbation of protein droplets in proximal tubule cells. Experiments were conducted to examine the retention of [ 14 C]d-limonene in male and female rat kidney, to determine whether d-limonene or one or more of its metabolites associates with the male rat-specific protein, alpha 2u-globulin, and if so, to identify the bound material. The results indicated that, 24 hr after oral administration of 3 mmol d-limonene/kg, the renal concentration of d-limonene equivalents was approximately 2.5 times higher in male rats than in female rats. Equilibrium dialysis in the presence or absence of sodium dodecyl sulfate indicated that approximately 40% of the d-limonene equivalents in male rat kidney associated with proteins in a reversible manner, whereas no significant association was observed between d-limonene equivalents and female rat kidney proteins. Association between d-limonene and male rat kidney proteins was characterized by high-performance gel filtration and reverse-phase chromatography. Gel filtration HPLC indicated that d-limonene in male rat kidney is associated with a protein fraction having a molecular weight of approximately 20,000. Separation of alpha 2u-globulin from other kidney proteins by reverse-phase HPLC indicated that d-limonene associated with a protein present only in male rat kidney which was definitively identified as alpha 2u-globulin by amino acid sequencing. The major metabolite associated with alpha 2u-globulin was d-limonene-1,2-oxide. Parent d-limonene was also identified as a minor component in the alpha 2u-globulin fraction

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

    Science.gov (United States)

    Aqai, Payam; Cevik, Ebru; Gerssen, Arjen; Haasnoot, Willem; Nielen, Michel W F

    2013-03-19

    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, a semi-automated competitive inhibition binding assay was combined with fast ultrahigh-performance-LC-electrospray ionization-triple-quadrupole-MS (UPLC-QqQ-MS). 17β-Testosterone-D3 was used as the stable isotope label of which the binding to rhSHBG-coated paramagnetic microbeads was inhibited by any other binding (designer) steroid. The assay was performed in a 96-well plate and combined with the fast LC-MS, 96 measurements could be performed within 4 h. The concentration-dependent inhibition of the label by steroids in buffer and dietary supplements was demonstrated. Following an adjusted bioaffinity isolation procedure, suspect extracts were injected into a chip-UPLC(NanoTile)-Q-time-of-flight-MS system for full-scan accurate mass identification. Next to known steroids, 1-testosterone was identified in three of the supplements studied and the designer steroid tetrahydrogestrinone was identified in a spiked supplement. The generic steroid-binding assay can be used for high-throughput screening of androgens, estrogens, and gestagens in dietary supplements to fight doping. When combined with chip-UPLC-MS, it is a powerful tool for early warning of unknown emerging rhSHBG bioactive designer steroids in dietary supplements.

  18. 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.

  19. Detection of sex hormone in serum and semen of patients with idiopathic oligospermia and its significance

    International Nuclear Information System (INIS)

    Wang Guohong; Xu Ruiji; Zhang Zhongshu; Wang Youji

    2005-01-01

    The objective of this study was to detect testosterone(T), free testosterone (FT) and sex hormone-binding globulin(SHBG) in serum and semen of patients with idiopathic oligospermia, and further analyze the relationship between T, FT, SHBG and idiopathic oligospermia. Blood and semen samples were collected from males of a normal control group and an idiopathic oligospermia group at 8:00-10:00 am. The sperm density in semen was detected by routine semen analysis, while T, FT, SHBG in serum and semen were detected by RIA. There were no significant differences in serum concentrations of T, FT, SHBG between normal control group [(30.03±13.07)nmol/L,(97.50±46.96)pmol/L, (40.37±16.73)nmol/L, respectively] and idiopathic oligspermia group [(28.11±11.54) nmol/L, (94.88±42.04) pmol/L, (41.61± 18.86)noml/LJ(all P>0. 05). There were significant differences in semsn concentrations of FT and SHBG between normal control group[(2.01±0.32) pmol/L, (0.17±0.21)nmol/L] and idiopathic oligspermia group [ (0.52±0.44) pmol/L, (0.22±0.15) nmol/LJ (P 0.05). Therefore, measurement of semsn FT, SHBG concentration could early reflect the function of tesis, which is useful for early diagnosis and treatment of idiopathic oligospermia. (authors)

  20. Relationships between obesity, lipids and fasting glucose in the menopause.

    Science.gov (United States)

    Netjasov, Aleksandra Simoncig; Vujović, Svetlana; Ivović, Miomira; Tancić-Gajić, Milina; Marina, Ljiljana; Barać, Marija

    2013-01-01

    Menopause leads to the development of central adiposity, a more atherogenic lipid profile and increased incidence of metabolic syndrome independent of age and other factors. The aim of the study was to investigate the relationships between anthropometric characteristics, sex hormones, lipids and fasting glucose in menopausal women. The study included 87 menopausal women, who where divided into groups according to two criteria: BMI > or = 26.7 kg/m2 and BMI > or = 25 kg/m2. Anthropometric characteristics and blood pressure were measured. Blood was taken at 08.00 h for fasting glucose, triglycerides, cholesterol, HDL, LDL, apolipoprotein A, apolipoprotein B, lipoprotein(a) (Lp(a)), C-reactive protein, fibrinogen, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol, progesterone, testosterone and sex hormone binding globulin (SHBG). Significant differences between groups were found for weight, BMI, waist, hips circumference, waist/hip ratio (WHR), systolic and diastolic blood pressure, Lp(a), FSH, LH, PRL (for systolic blood pressure p fasting glucose (p obese and overweight women with BMI > or = 26.7 kg/m2 significant negative correlations were found for FSH and glucose, SHBG and LDL, SHBG and total cholesterol, SHBG and glucose, BMI and HDL, WC and HDL. In obese and overweight women with BMI > or = 25 kg/m2 significant negative correlations were found for BMI and HDL, waist circumference (WC) and HDL, WHR and HDL, FSH and glucose, SHBG and glucose; significant positive correlations were between BMI and glucose, WC and glucose and WHR with triglycerides. Gaining weight and decreased SHBG are related to dyslipidemia and increased fasting glucose confirming increased incidence of metabolic abnormalities in the menopause.

  1. Comparison of the effects of ovarian cauterization and gonadotropin-releasing hormone agonist and oral contraceptive therapy combination on endocrine changes in women with polycystic ovary disease.

    Science.gov (United States)

    Taskin, O; Yalcinoglu, A I; Kafkasli, A; Burak, F; Ozekici, U

    1996-06-01

    To study the effects of laparoscopic ovarian cauterization and combination of long-acting GnRH agonist (GnRH-a) and oral contraceptive (OC) therapy on endocrine changes in women with clomiphene citrate (CC)- resistant polycystic ovary disease (PCOD). Prospective, randomized. University-based infertility clinic. Seventeen women with CC-resistant PCOD were included randomly in the study to either laparoscopic ovarian cautery or GnRH-a and OC therapy for 3 months. Serum concentrations of LH, FSH, androstenedione (A), T, and sex hormone-binding globulin (SHBG) were determined before each therapeutic approach and during the follicular phase of first menstrual cycle after the cessation of each treatment. The mean serum concentrations and the clinical profiles were similar in both groups. Both groups showed significant changes in LH, FSH, A, T, and SHBG compared with pretreatment levels. There were no significant differences in the final concentrations of LH, FSH, and A between the two study groups after each treatment, whereas T and SHBG levels were significantly different in the goserelin and OC group. The decrease in LH and increase in SHBG serum concentrations were greater in the goserelin and OC-treated women [-59% and + 5.9% versus - 70% and + 13.5%, respectively]. Although the SHBG concentration increased in both groups, the serum SHBG concentration of the goserelin and OC group was significantly higher than the other group. Both therapeutic modalities revealed similar effects on the endocrine profiles in women with CC-resistant PCOD. Considering the invasiveness, cost, and potential complications of laparoscopic ovarian cauterization, noninvasive medical treatment with GnRH-a and OC combination may be more effective in restoring the optimal follicular environment in women with PCOD.

  2. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Souza, A.J. [Laboratório de Química e Função de Proteínas e Peptídeos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, RJ (Brazil); Ferreira, A.T.S.; Perales, J.; Beghini, D.G. [Laboratório de Toxinologia, Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ (Brazil); Fernandes, K.V.S.; Xavier-Filho, J.; Venancio, T.M.; Oliveira, A.E.A. [Laboratório de Química e Função de Proteínas e Peptídeos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense, Campos dos Goytacazes, RJ (Brazil)

    2011-01-27

    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 chitinbinding 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.

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

    International Nuclear Information System (INIS)

    Souza, A.J.; Ferreira, A.T.S.; Perales, J.; Beghini, D.G.; Fernandes, K.V.S.; Xavier-Filho, J.; Venancio, T.M.; Oliveira, A.E.A.

    2011-01-01

    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 chitinbinding 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

  5. Coupling of dextrans conjugated with boron to gamma globulin: a model for NCT

    International Nuclear Information System (INIS)

    Elmore, J.J. Jr.; Borg, D.C.; Micca, P.; Gabel, D.

    1983-01-01

    Our project is to meet more effectively the well known primary requirement for treatment with boron-10 neutron capture therapy (NCT): namely, the selective localization of a sufficient amount of boron in or on target cells. Monoclonal antibodies (MCA) to tumor-associated antigens are attractive targeting carriers for boron-10 in terms of the needed selective localization. However the densities of surface receptors on tumor cells have seemed deficient to achieve successful NCT. If one seeks the necessary radiotherapeutic ratios by increasing the numbers of boron atoms or carborane cages bound per MCA, then inactivation of the antibody can occur through loss of receptor specificity and/or by precipitation of the protein. To achieve the goal of overcoming the limitations of antibody binding capacity, we have elected to use water-soluble dextrans as intermediate carriers. This permits each MCA molecule to target many atoms of boron-10 to the specified antigenic receptors while only 5 to 10 of the amino acid residues of the protein are conjugated by dextrans carrying boron-10

  6. Cloning of cDNA sequences encoding cowpea (Vigna unguiculata) vicilins: Computational simulations suggest a binding mode of cowpea vicilins to chitin oligomers.

    Science.gov (United States)

    Rocha, Antônio J; Sousa, Bruno L; Girão, Matheus S; Barroso-Neto, Ito L; Monteiro-Júnior, José E; Oliveira, José T A; Nagano, Celso S; Carneiro, Rômulo F; Monteiro-Moreira, Ana C O; Rocha, Bruno A M; Freire, Valder N; Grangeiro, Thalles B

    2018-05-27

    Vicilins are 7S globulins which constitute the major seed storage proteins in leguminous species. Variant vicilins showing differential binding affinities for chitin have been implicated in the resistance and susceptibility of cowpea to the bruchid Callosobruchus maculatus. These proteins are members of the cupin superfamily, which includes a wide variety of enzymes and non-catalytic seed storage proteins. The cupin fold does not share similarity with any known chitin-biding domain. Therefore, it is poorly understood how these storage proteins bind to chitin. In this work, partial cDNA sequences encoding β-vignin, the major component of cowpea vicilins, were obtained from developing seeds. Three-dimensional molecular models of β-vignin showed the characteristic cupin fold and computational simulations revealed that each vicilin trimer contained 3 chitin-binding sites. Interaction models showed that chito-oligosaccharides bound to β-vignin were stabilized mainly by hydrogen bonds, a common structural feature of typical carbohydrate-binding proteins. Furthermore, many of the residues involved in the chitin-binding sites of β-vignin are conserved in other 7S globulins. These results support previous experimental evidences on the ability of vicilin-like proteins from cowpea and other leguminous species to bind in vitro to chitin as well as in vivo to chitinous structures of larval C. maculatus midgut. Copyright © 2018. Published by Elsevier B.V.

  7. Serum testosterone concentrations in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C

    1987-01-01

    Median serum testosterone concentration of men with alcoholic cirrhosis (n = 216) did not differ significantly from normal controls (n = 51), but serum testosterone concentrations varied by a factor 43.9 in patients compared to 3.2 in controls (P less than .001). Nineteen percent of the patients...... had serum testosterone concentrations above 30 nmol/L. Serum concentrations of sex-hormone-binding globulin (SHBG) were significantly (P less than .001) raised, and serum concentrations of calculated nonprotein-bound and non-SHBG-bound testosterone were significantly (P less than .001) decreased...... in patients compared to normal control values. A number of background variables were analyzed with reference to serum testosterone concentrations by means of multiple regression techniques after having divided the patients into groups (A, B, C) with decreasing liver function by a modification of the Child...

  8. Vitamin D deficiency and low ionized calcium are linked with semen quality and sex steroid levels in infertile men

    DEFF Research Database (Denmark)

    Jensen, Martin Blomberg; Lawaetz, Jacob Gerner; Andersson, Anna-Maria

    2016-01-01

    STUDY QUESTION: Are low vitamin D levels linked with semen quality and sex steroids in infertile men? SUMMARY ANSWER: Infertile men with vitamin D deficiency had lower sperm motility, total numbers of motile sperm, Inhibin B, sex-hormone-binding-globulin (SHBG) and testosterone/estradiol ratio......, but higher levels of free sex steroids, than infertile men with normal vitamin D levels. WHAT IS KNOWN ALREADY: Low vitamin D levels have been associated with decreased sperm motility in healthy men, but a relationship between vitamin D and calcium with semen quality and especially sex steroids has not been...... infertile men, consecutively referred to our tertiary andrological centre for fertility workup, underwent a physical examination and had semen quality assessed based on two samples and blood analysed for serum testosterone, SHBG, estradiol, inhibin B, luteinizing hormone, follicle-stimulating hormone (FSH...

  9. 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 < 0.001) levels were still positively associated with BLLs in men. Meanwhile, significant positive associations were found for BLLs with SHBG (P for trend = 0.002), FSH (P for trend = 0.001) and LH (P for trend = 0.026) levels in postmenopausal women. Additionally, the association between BLL and SHBG was modified by dysglycaemia (P for interaction = 0.03) in postmenopausal women. In conclusion, BLLs were associated with 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.

  10. 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

    , 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......Background: It is not known why some foods sensitizing via the gastrointestinal tract are prevalent allergenic foods and others are not. Eating habits, processing, and the food matrix have been suggested to influence the allergenicity of a given food. Factors related to protein structure...... 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...

  11. Repair of UV-induced DNA damage in aplastic anaemia: Changes after treatment with antilymphocyte globulin (ALG)

    Energy Technology Data Exchange (ETDEWEB)

    Kovacs, E.; Nissen, C.; Speck, B.; Signer, E.

    1988-01-01

    The extent of DNA-repair induced by UV-C irradiation was measured in peripheral unstimulated lymphocytes of 24 patients with aplastic anaemia at different stages of disease and compared with the results obtained in 92 controls. As parameter of the DNA-repair synthesis, the incorporation of (/sup 3/H)thymidine in the presence of 2 mmol/l hydroxyurea (HU) was taken. Of 19 patients tested after treatment with antilymphocyte globulin (ALG), 5 were in complete autologous haemopoietic remission, defined as > 1000 granulocytes/mm/sup 3/, > 100 000 platelets/mm/sup 3/ and a nontransfused haemoglobin value > 10 g%. 14 patients were in partial remission, defined as improvement of haemopoietic function, not meeting the criteria for complete remission. 4/5 patients in complete remission had normal DNA-repair synthesis, compared to 4/14 patients in partial remission. In 92 controls, a normal level was found in 70 cases. In 4/5 patients examined at diagnosis and at various intervals after ALG-treatment, DNA-repair synthesis was low at diagnosis. It increased after therapy and paralleled improvement of haemopoietic function to some extent. It is suggested that in aplastic anaemia there are different populations of lymphocytes with differing DNA-repair capacity; ALG treatment seems to favour expansion of the normal population, which is associated with improvement of haemopoietic function.

  12. 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.

  13. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words.

    Science.gov (United States)

    Mirick, G R; Bradt, B M; Denardo, S J; Denardo, G L

    2004-12-01

    The United States Food and Drug Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ((90)yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ((131)I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) anti-CD20 MAbs for use in radioimmunotherapy (RIT) of non-Hodgkin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, assays were developed to determine HAGA (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to ''humanize'' MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades.

  14. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words

    International Nuclear Information System (INIS)

    Mirick, G. R.; Bradt, B. M.; Denardo, S. J.; Denardo, G. L.

    2004-01-01

    The United States Food and Drugs Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ( 9 0yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ( 1 31I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) antiCD20 MAns for use in radioimmunotherapy (RIT) of non-Hodgikin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, essays were developed to determine HAGE (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to humanize MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades

  15. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words

    Energy Technology Data Exchange (ETDEWEB)

    Mirick, G. R.; Bradt, B. M.; Denardo, S. J.; Denardo, G. L. [Calfornia Univ., Sacramento (United States). Davis Medical Center

    2004-12-01

    The United States Food and Drugs Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ({sup 9}0yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ({sup 1}31I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) antiCD20 MAns for use in radioimmunotherapy (RIT) of non-Hodgikin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, essays were developed to determine HAGE (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to humanize MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades.

  16. Analysis of infusion-site reactions in renal transplant recipients receiving peripherally administered rabbit antithymocyte globulin as compared with basiliximab.

    Science.gov (United States)

    Erickson, Abbie L; Roberts, Keri; Malek, Sayeed K; Chandraker, Anil K; Tullius, Stefan G; Gabardi, Steven

    2010-06-01

    Antithymocyte globulin rabbit (r-ATG) has been used for the treatment and prevention of acute rejection in renal transplant recipients (RTR). Current manufacturer recommendations for r-ATG dictate the need for administration through a high-flow vein (central line). Previous studies have shown peripheral administration of r-ATG to be safe; however, these studies suggest the co-administration of heparin and hydrocortisone and did not compare the infusion-site reaction rates to a control group. A retrospective analysis was conducted of adult RTR receiving r-ATG or basiliximab between January 2004 and October 2006. Each agent was administered through a dedicated peripheral line. The primary endpoint was the incidence of infusion-site reactions. Other endpoints included the need to replace the intravenous catheter and the incidence of systemic thrombosis within 1 month of transplantation. During the study period, 152 peripheral infusions of r-ATG and 92 peripheral infusions of basiliximab were administered. No difference in infusion-site reactions was noted between the groups. There was also no difference either in the need for peripheral line replacement or the rates of systemic thrombosis. Peripheral administration of r-ATG is safe and can be infused without concomitant heparin and hydrocortisone. This method of r-ATG infusion was shown to be as safe as peripherally administered basiliximab.

  17. Methyl isobutyl ketone (MIBK) induction of α2u-globulin nephropathy in male, but not female rats

    International Nuclear Information System (INIS)

    Borghoff, S.J.; Hard, G.C.; Berdasco, N.M.; Gingell, R.; Green, S.M.; Gulledge, W.

    2009-01-01

    Male F-344 rats were administered corn oil (vehicle control), d-limonene (positive control, 300 mg/kg), or MIBK (1000 mg/kg) and female F-344 rats corn oil (vehicle control) or MIBK for 10 consecutive days by oral gavage. Approximately 24 h after the final dose the kidneys were excised and the left kidney prepared and evaluated for histological changes including protein (hyaline) droplet accumulation, immunohistochemical staining for α2u-globulin (α2u), and proliferating cell nuclear antigen (PCNA) to quantitate renal cell proliferation. The right kidney was prepared for quantitation of total protein and α2u using an ELISA. MIBK elicited an increase in protein droplets, accumulation of α2u, and renal cell proliferation in male, but not female rats, responses characteristic of α2u-mediated nephropathy. MIBK produced identical histopathological changes in the male rat kidney when compared to d-limonene, an acknowledged inducer of α2u-nephropathy except that the grade of severity tended to be slightly lower with MIBK. MIBK did not induce any effects in female rats. Therefore, renal histopathology, along with the other measures of α2u accumulation, provides additional weight of evidence to support the inclusion of MIBK in the category of chemicals exerting renal effects through a α2u-nephropathy-mediated mode-of-action

  18. Induction of specific unresponsiveness to heart allografts in mongrel dogs treated with total lymphoid irradiation and antithymocyte globulin

    International Nuclear Information System (INIS)

    Strober, S.; Modry, D.L.; Hoppe, R.T.

    1984-01-01

    The survival of heterotopic heart allografts was determined in mongrel dogs treated with total lymphoid irradiation (TLI) alone or in combination with other immunosuppressive agents. TLI alone (total dose, 1800 rad) minimally prolonged graft survival as compared with untreated controls. However, marked synergy was observed when TLI was combined with a 10-day post-transplant course of rabbit anti-dog thymocyte globulin (ATG). Approximately 40% of recipients given TLI and ATG showed specific unresponsiveness, as judged by the lack of rejection on serial biopsies for more than 1 year and the prompt rejection of third party hearts. The addition of post-transplant azathioprine (90 to 180 days) to the TLI and ATG regimen increased the mortality of recipients and reduced the fraction of dogs showing specific unresponsiveness. Infusion of donor bone marrow cells at the time of heart transplantation failed to induced specific unresponsiveness in recipients given TLI alone or TLI in combination with post-transplant methotrexate, cyclosporine A, or ATG. The results indicate that the combination of TLI and a brief course of ATG without marrow transplantation was the most effective regimen for the induction of specific unresponsiveness in mongrel dogs

  19. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Semen quality and reproductive hormones before orchiectomy in men with testicular cancer

    DEFF Research Database (Denmark)

    Petersen, P M; Skakkebaek, N E; Vistisen, K

    1999-01-01

    cancer (TGCC) investigated before orchiectomy, semen analysis was carried out in 63 patients and hormonal investigations, including measurement of follicle-stimulating hormone, luteinizing hormone (LH), testosterone, estradiol, sex hormone-binding globulin (SHBG), inhibin B, and human chorionic...... (group 2). Group 3 comprised 141 men employed in a Danish company who served as controls in the comparison of semen parameters. As a control group in hormone investigations, 193 men were selected randomly from the Danish National Personal Register to make up group 4. RESULTS: We found significantly lower...

  1. Preorchiectomy Leydig Cell Dysfunction in Patients With Testicular Cancer

    DEFF Research Database (Denmark)

    Bandak, Mikkel; Jørgensen, Niels; Juul, Anders

    2017-01-01

    BACKGROUND: Little is known about preorchiectomy Leydig cell function in patients with testicular germ cell cancer (TGCC). The aim was to estimate the prevalence of preorchiectomy Leydig cell dysfunction and evaluate factors associated with this condition in a cohort of patients with TGCC. PATIENTS...... AND METHODS: We evaluated luteinizing hormone (LH), total testosterone (TT), calculated free T (cFT), estradiol, and sex hormone-binding globulin (SHBG) preorchiectomy in 561 patients with TGCC and compared with 561 healthy controls. We calculated TT/LH and cFT/LH ratios and constructed bivariate charts of TT...

  2. Negligible effects of nonesterified fatty acids on serum thyroxine analysis by competitive protein-binding radioassay on Sephadex and by radioimmunoassay

    International Nuclear Information System (INIS)

    Alexander, N.M.; Nishimoto, M.

    1978-01-01

    Values for thyroxine by our competitive protein-binding assay on Sephadex (I) and by radioimmmunoassy (II) were identical for sera containing markedly increased concentrations of endogenous nonesterified fatty acids. Addition of as much as 5 mmol of long-chain saturated fatty acids per liter to normal serum had no significant effect on the thyroxine values by I; larger concentrations (10 mmol/liter) spuriously increased values by 20 to 30%. Added unsaturated fatty acids (1 mmol/liter) were without effect on procedure I, but spurious elevations in thyroxine appeared when concentrations were further increased up to 10 mmol/liter. The spurious effects by 2 to 5 mmol of added oleate and arachidonate (the most potent inhibitor of thyroxine binding to thyroxine-binding globulin) per liter could be reversed by washing the Sephadex columns with additional barbital buffer before binding with thyroxine-binding globulin (a step that is done on the gel). Three different II procedures were unaffected by as much as 5 mmol of added fatty acids per liter, but moderate spurious increases were noted with 10 mmol of oleate per liter. We conclude that method I is reliable for thyroxine analysis in nearly all sera from human subjects, because the concentrations of unsaturated fatty acids present either in vitro or in vivo are seldom large enough to interfere

  3. Predictors of early mortality after rabbit antithymocyte globulin as first-line treatment in severe aplastic anemia.

    Science.gov (United States)

    Atta, Elias H; Lima, Carlos B L; Dias, Danielle S P; Clé, Diego V; Bonduel, Mariana M; Sciuccati, Gabriela B; Medeiros, Larissa A; Oliveira, Michel M; Salvino, Marco A; Garanito, Marlene P; Blum Fonseca, Patricia B; Saad, Sara Teresinha O; Calado, Rodrigo T; Scheinberg, Phillip

    2017-11-01

    Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 10 9 /L (OR 7.64, P  35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 10 9 /L (OR 2.65, P < 0.001), and lack of response to rabbit ATG (OR 11.40, P < 0.001) were independently associated with mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Outcomes of Optimized over Standard Protocol of Rabbit Antithymocyte Globulin for Severe Aplastic Anemia: A Single-Center Experience

    Science.gov (United States)

    Ge, Meili; Shao, Yingqi; Huang, Jinbo; Huang, Zhendong; Zhang, Jing; Nie, Neng; Zheng, Yizhou

    2013-01-01

    Background Previous reports showed that outcome of rabbit antithymocyte globulin (rATG) was not satisfactory as the first-line therapy for severe aplastic anemia (SAA). We explored a modifying schedule of administration of rATG. Design and Methods Outcomes of a cohort of 175 SAA patients, including 51 patients administered with standard protocol (3.55 mg/kg/d for 5 days) and 124 cases with optimized protocol (1.97 mg/kg/d for 9 days) of rATG plus cyclosporine (CSA), were analyzed retrospectively. Results Of all 175 patients, response rates at 3 and 6 months were 36.6% and 56.0%, respectively. 51 cases received standard protocol had poor responses at 3 (25.5%) and 6 months (41.2%). However, 124 patients received optimized protocol had better responses at 3 (41.1%, P = 0.14) and 6 (62.1%, P = 0.01). Higher incidences of infection (57.1% versus 37.9%, P = 0.02) and early mortality (17.9% versus 0.8%, P<0.001) occurred in patients received standard protocol compared with optimized protocol. The 5-year overall survival in favor of the optimized over standard rATG protocol (76.0% versus. 50.3%, P<0.001) was observed. By multivariate analysis, optimized protocol (RR = 2.21, P = 0.04), response at 3 months (RR = 10.31, P = 0.03) and shorter interval (<23 days) between diagnosis and initial dose of rATG (RR = 5.35, P = 0.002) were independent favorable predictors of overall survival. Conclusions Optimized instead of standard rATG protocol in combination with CSA remained efficacious as a first-line immunosuppressive regimen for SAA. PMID:23554855

  7. Induction by anti-thymocyte globulins in kidney transplantation: a review of the literature and current usage.

    Science.gov (United States)

    Malvezzi, Paolo; Jouve, Thomas; Rostaing, Lionel

    2015-10-01

    Preventing acute rejection (AR) after kidney transplantation is of utmost importance because an AR can have a negative impact on long-term allograft survival. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO, and Web of Science have been searched. At the moment this can be done by using rabbit anti-thymocyte globulins (rATGs) as an induction therapy. However, because rATGs are associated with some deleterious side-effects, such as the opportunistic infections cytomegalovirus (CMV) and de novo post-transplant cancer, it is very important they are used optimally, i.e., at minimal doses that avoid many side-effects but still retain optimal treatment efficacy. Recent data show that the risk of CMV infection can be minimized using tacrolimus plus everolimus, and not tacrolimus plus mycophenolic acid, as the maintenance immunosuppression. The use of rATG is particularly valuable in; (a) sensitized patients; (b) in recipients from an expanded-criteria donor, thus enabling the introduction of calcineurin inhibitors at reduced doses; and (c) for patients where steroid avoidance is contemplated. However, we also need to consider that rATG may increase the risk of de novo cancer, even though recent data indicate this is unlikely and that any risk can be reduced by using mammalian target of rapamycin (mTOR) inhibitors instead of mycophenolic acid combined with low-dose calcineurin inhibitors. Even though rATGs do not improve long-term kidney-allograft survival, they may help reduce calcineurin-inhibitor dosage during the early post-transplant period and minimize the risk of AR.

  8. Single-shot antithymocyte globulin (ATG) induction for pancreas/kidney transplantation: ATG-Fresenius versus Thymoglobulin.

    Science.gov (United States)

    Schulz, T; Papapostolou, G; Schenker, P; Kapischke, M

    2005-03-01

    Single-shot antithymocyte globulin (ATG) prior to reperfusion followed by tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisolone (PRD) is an established induction therapy in simultaneous pancreas kidney transplant (SPK) recipients. We retrospectively analyzed 6-month data from 105 patients who received their first SPK. From January 1996 to December 2000, ATG-Fresenius was used. Since January 2001, Thymoglobulin has been administered. In the first group, 58 patients were treated with ATG-Fresenius (4-6 mg/kg body weight). In the second group, 47 patients received Thymoglobulin (1.5-2.5 mg/kg body weight). HLA-mismatch was comparable. After an observation period of 6 months, patients, kidney, and pancreas graft survival is 98.3%, 96.6%, and 93.1% in group I and 97.9%, 97.9%, and 85.1% in group II, respectively. In each group, one death with functioning graft (DWFG) was observed. Twenty (34.5%) acute rejection episodes (AR) were observed (18 patients) in group I. They were treated with steroids (n = 16) or steroids/OKT3 (n = 4). One kidney graft failure was observed due to rejection and one due to DWFG. Four pancreas grafts were lost (thrombosis, n = 2; AR, n = 1; DWFG, n = 1). In group II, 15 AR (31.9%) were seen in 12 patients and were treated with steroids (n = 12), steroids/ATG (n = 1), or steroids/OKT3 (n = 2). Seven pancreas (thrombosis, n = 5; rejection, n = 1; DWFG, n = 1) and one kidney (DWFG, n = 1) graft losses occurred. These data clearly establish that single-shot ATG prior to reperfusion, followed by TAC, MMF, and PRD results in a low incidence of AR (34.5% in group I and 31.9% in group II) after SPK. Only 6.9% (group I) and 6.4% (group II) of the patients received antibodies for rejection treatment.

  9. Comparison of daclizumab, an interleukin 2 receptor antibody, to anti-thymocyte globulin-Fresenius induction therapy in kidney transplantation.

    Science.gov (United States)

    Abou-Jaoude, Maroun M; Ghantous, Imad; Almawi, Wassim Y

    2003-07-01

    The efficacy and safety of daclizumab and anti-thymocyte globulin-Fresenius (ATG-F) as induction therapy in kidney transplantation (KT) were investigated in 45 KT performed in our center between March and May 2002. Group II (n=10) received daclizumab as induction therapy, and Group I (n=35) were induced with a single intraoperative bolus therapy of ATG-F. All patients were at low-risk, and the recipient and donor demographics, as well the immunosuppression regimen employed were comparable in both groups. Drug safety, assessed by the occurrence of side effects, was almost comparable in the two groups, except for more thrombocytopenia in Group II (P<0.0004). Acute rejection (AR) occurred in 10% in Group I and 11.4% in Group II (P=NS). There were more infections in Group II (42.8%) than in Group I (10%) (P<0.009). Bacterial and viral infections were more common in Group II (69 and 23%) than in Group I (10 and 0%) (P<0.05). The hospital stay was similar in both groups. Mean serum creatinine levels upon discharge, at 1, 3 and 6 months were: 1.23+/-0.11, 1.21+/-0.06, 1.25+/-0.11 and 1.35+/-0.08 in Group I and 2.18+/-0.43, 1.49+/-0.16, 1.49+/-0.16 and 1.35+/-0.08 in Group II, respectively. While better serum creatinine levels were observed in Group I upon discharge (P<0.048), this was due to the presence of more sensitized patients in Group II. The 6 months actuarial patient and graft survival were identical in both groups (100 and 100%, respectively). Although both daclizumab and ATG-F were effective and safe as induction therapy in KT, less bacterial and viral infections and lower early serum creatinine levels were noted in daclizumab-treated patients.

  10. Induction treatment with rabbit antithymocyte globulin versus basiliximab in renal transplant recipients with planned early steroid withdrawal.

    Science.gov (United States)

    Martin, Spencer T; Roberts, Keri L; Malek, Sayeed K; Tullius, Stefan G; Vadivel, Nidyanandh; De Serres, Sacha; Grafals, Monica; Elsanjak, Abdelaziz; Filkins, Beth Anne; Chandraker, Anil; Gabardi, Steven

    2011-06-01

    To compare the safety and efficacy of rabbit antithymocyte globulin (r-ATG) with basiliximab in renal transplant recipients for whom an early steroid withdrawal (ESW) regimen was planned. Single-center, retrospective, cohort study. Tertiary care medical center, including inpatient hospital stays and outpatient nephrology clinics. Ninety-nine consecutive adult recipients of living- or deceased-donor renal transplants between January 1, 2004, and December 31, 2007, in whom ESW was planned and who received either r-ATG or basiliximab; patients receiving an extended-criteria kidney donation or a donation after cardiac death were excluded. All patients received mycophenolate mofetil and tacrolimus as maintenance therapy with planned ESW. Induction therapy was either r-ATG 1.5 mg/kg/day for 4 days (68 patients) or basiliximab 20 mg on postoperative days 0 and 4 (31 patients). The primary composite end point of biopsy-proven acute rejection (BPAR), graft loss, and death occurred in 6 patients (9%) and 9 patients (29%) in the r-ATG and basiliximab groups at 1 year after transplantation, respectively (p=0.01), with rates of 7% (5/68 patients) and 26% (8/31 patients) for BPAR (p=0.02), 0% and 3% (1/31 patients) for graft loss (p=0.31), and 2% (1/68 patients) and 0% for patient death (p>0.99). Average time to first BPAR was significantly longer in the r-ATG group (mean ± SD 151.4 ± 82.9 vs 53.6 ± 68.4 days, p<0.01). Kidney function at 12 months was similar between the two groups. Rabbit-ATG was associated with a lower frequency and delayed onset of BPAR compared with basiliximab in renal transplant recipients who received an ESW regimen.

  11. Apoptotic effects of antilymphocyte globulins on human pro-inflammatory CD4+CD28- T-cells.

    Directory of Open Access Journals (Sweden)

    Christina Duftner

    Full Text Available BACKGROUND: Pro-inflammatory, cytotoxic CD4(+CD28(- T-cells with known defects in apoptosis have been investigated as markers of premature immuno-senescence in various immune-mediated diseases. In this study we evaluated the influence of polyclonal antilymphocyte globulins (ATG-Fresenius, ATG-F on CD4(+CD28(- T-cells in vivo and in vitro. PRINCIPAL FINDINGS: Surface and intracellular three colour fluorescence activated cell sorting analyses of peripheral blood mononuclear cells from 16 consecutive transplant recipients and short-term cell lines were performed. In vivo, peripheral levels of CD3(+CD4(+CD28(- T-cells decreased from 3.7 ± 7.1% before to 0 ± 0% six hours after ATG-F application (P = 0.043 in 5 ATG-F treated but not in 11 control patients (2.9 ± 2.9% vs. 3.9 ± 3.0%. In vitro, ATG-F induced apoptosis even in CD4(+CD28(- T-cells, which was 4.3-times higher than in CD4(+CD28(+ T-cells. ATG-F evoked apoptosis was partially reversed by the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz-Val-Ala-Asp(OMe-fluoromethylketone (zVAD-fmk and prednisolon-21-hydrogensuccinate. ATG-F triggered CD25 expression and production of pro-inflammatory cytokines, and induced down-regulation of the type 1 chemokine receptors CXCR-3, CCR-5, CX3CR-1 and the central memory adhesion molecule CD62L predominately in CD4(+CD28(- T-cells. CONCLUSION: In summary, in vivo depletion of peripheral CD3(+CD4(+CD28(- T-cells by ATG-F in transplant recipients was paralleled in vitro by ATG-F induced apoptosis. CD25 expression and chemokine receptor down-regulation in CD4(+CD28(- T-cells only partly explain the underlying mechanism.

  12. Fulltext PDF

    Indian Academy of Sciences (India)

    2012-04-03

    Apr 3, 2012 ... globulin (SHBG), the principal carrier protein for oestrogen. Lower levels of ... esized to play a role in the obesity-disease associations. In insulin ... Mini-review ..... strategic drug delivery to the brain (SDDB): development of.

  13. Total iron binding capacity

    Science.gov (United States)

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

  14. 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.

  15. Synthesis and preliminary study of 99mTc-mercaptoacetyl-triglycine (99mTc-MAG3) for radiolabeling of immune globulins

    International Nuclear Information System (INIS)

    Reyes, L.; Navarrete, M.

    2001-01-01

    The synthesis of a complex molecule with its coordination center composed by a triamide monomercaptide tetradentate set of donor groups plus a phenyl-acetyl group as protector group of a sulphur atom is reported. This compound has been mixed with immune globulin G, labeled with 99m Tc and purified by high resolution liquid chromatography (HRLC). The biological behavior of this labeled compound was evaluated with mice of Balb-C origin, showing the biological properties of a protein. This molecule might be another option for radio-immuno-scintigraphic analysis when using proteins of antigenic nature. (author)

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

    DEFF Research Database (Denmark)

    Dam, Svend Secher; Thaysen-Andersen, Morten; Stenkjær, Eva

    2013-01-01

    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...

  17. Serum globulin electrophoresis

    Science.gov (United States)

    ... plasma proteins. In: Baynes JW, Dominiczak MH, eds. Medical Biochemistry . 4th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 4. Rajkumar SV. Plasma cell disorders. In: Goldman L, Schafer AI, ... . 25th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 187.

  18. Effects of obesity, total fasting and re-alimentation on L-thyroxine (T4), 3,5,3'-L-triiodothyronine (T3), 3,3',5'-L-triiodothyronine (rT3), thyroxine binding globulin (TBG), cortisol, thyrotrophin, cortisol binding globulin (CBG), transferrin, alpha 2-haptoglobin and complement C'3 in serum.

    Science.gov (United States)

    Scriba, P C; Bauer, M; Emmert, D; Fateh-Moghadam, A; Hofmann, G G; Horn, K; Pickardt, C R

    1979-08-01

    The effects of total fasting for 31 +/- 10 days followed by re-alimentation with an 800 calorie diet on thyroid function, i.e. T4,T3,rT3,RT3U (resin T3 uptake), and TSH, and on TBG levels in serum were studied sequentially in obese hospitalized patients (N=18). Additionally, cortisol, growth hormone, prolactin, parathyrin and free fatty acids were followed as hormonal and metabolic parameters, respectively. Further, CBG, transferrin, alpha 2-haptoglobin and complement C'3 were measured as representatives of other serum proteins. Results before fasting: T4, T3, TBG, cortisol, CBG, alpha 2-haptoglobin and complement C'3 of the obese patients were elevated when compared with healthy normal weight controls, whereas rT3, T4/TBG ratio, T3/TBG ratio, TSH, coritsol/cbg ratio, growth hormone, prolactin, parathyrin and transferrin of the obese group were normal. RT3U and fT4 index were decreased in the obese patients. Results during fasting: Significant decreases were observed during fasting for the following parameters -- T3, TBG, T3/TBG ratio, transferrin, alpha 2-haptoglobin complement C'3. rT3, T4/TBG ratio, RT3U, fT4 index and FFA increased. T4, tsh response to TRH stimulation, cortisol, CBG, cortisol/cbg ratio, parathyrin, growth hormone and prolactin did not change. Results during re-alimentation: T3, TBG, T3/TBG ratio, TSH response to TRH, transferrin, alpha 2-haptoglobin and complement C'3 increased. Conversely, fT3, RT3U, FFA, cortisol and cortisol/cbg ratio decreased whereas the other parameters did not change. 1) There is no evidence for primary hypothyroidism in obese patients during prolonged fasting and re-alimentation. 2) The rapid decrease of T3 and increase of RT3U after initiation of fasting are not fully explained by the observed slower decreases in TBG. 3) The alterations of T3, rT3 and RT3U resemble in their kinetics the changes in FFA levels. 4) Fasting reduced the levels of only certain serum proteins, interestingly TBG, transferrin, alpha 2-haptoglobin and complement C'3, all of which, except transferrin, are elevated in obesity. 5) The magnitude of the observed decreases does not suggest any clinically relevant deficiencies in serum proteins. 6) Re-alimentation reverses rapidly all observed changes.

  19. 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.

  20. Prostate cancer risk: the significance of differences in age related changes in serum conjugated and unconjugated steroid hormone concentrations between Arab and Caucasian men.

    Science.gov (United States)

    Kehinde, E O; Akanji, A O; Memon, A; Bashir, A A; Daar, A S; Al-Awadi, K A; Fatinikun, T

    2006-01-01

    Factors responsible for the low incidence of clinical prostate cancer (3-8/100,000 men/year) in the Arab population remain unclear, but may be related to changes in steroid hormone metabolism. We compared the levels of serum conjugated and unconjugated steroids between Arab and Caucasian populations, to determine if these can provide a rational explanation for differences in incidence of prostate cancer between the two populations. Venous blood samples were obtained from 329 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-80 years. Samples were also obtained from similar Arab men with newly diagnosed prostate cancer or benign prostatic hyperplasia (BPH). The samples were taken between 8:00 am and 12:00 noon. Serum levels of total testosterone, (TT), sex hormone binding globulin (SHBG), free androgen index (FAI); adrenal C19-steroids, dehydroepiandrosterone sulphate (DHEAS) and androstenedione (ADT) were determined using Immulite kits (Diagnostic Systems Laboratories Inc, Webster Texas, USA). The results obtained in Arab men were compared with those reported for similarly aged Chinese, German and White USA men. In all four ethnic groups, median TT and FAI declined with age, while SHBG increased with age. However, the mean TT and SHBG was significantly lower (p Arab men (p Arabs (p Arabs. There was no significant difference in mean serum levels of DHEAS between German and USA men. Similarly, there was no significant difference in the level of the hormones between Arab and Chinese men. Arab men with newly diagnosed prostate cancer had high serum TT, SHBG and DHEAS compared to those without the disease. The mean TT and SHBG was significantly lower in Arab men compared to Caucasian men especially in early adulthood. Caucasians have significantly higher serum levels of the precursor androgens DHEAS and ADT especially in early adulthood compared to Arab men. These observations of low circulating androgens and their adrenal precursors in

  1. [FAB immunoglobulin fragments. I. The comparative characteristics of the serological and virus-neutralizing properties of a gamma globulin against tick-borne encephalitis and of the FAB fragments isolated from it].

    Science.gov (United States)

    Barban, P S; Minaeva, V M; Pantiukhina, A N; Startseva, M G

    1976-06-01

    A comparative study was made of the serological properties and virus-neutralizing activity of antiencephalitis gamma-globulin and Fab-fragments isolated from it by gel-filtration. Horse immunoglobulins against the autumno-summer tick-borne encephalitis virus could be disintegrated with the aid of papaine to monovalent Fab-fragments which (according to the complement fixation reaction, the test of suppression of the complement fixation, and the HAIT) retained the serological activity whose level was compared with that of the serological activity of gamma-globulin. Fab-fragments possessed a marked virus-neutralizing activity. The mean value of a logarithm of the neutralization index was 2.65 +/- 0.2 for Fab-fragments and 3.74 +/- 0.38 for gamma-globulin (P less than 0.01).

  2. Feature Binding in Zebrafish

    Directory of Open Access Journals (Sweden)

    P Neri

    2012-07-01

    Full Text Available Binding operations are primarily ascribed to cortex or similarly complex avian structures. My experiments show that the zebrafish, a lower vertebrate lacking cortex, supports visual feature binding of form and motion for the purpose of social behavior. These results challenge the notion that feature binding may require highly evolved neural structures and demonstrate that the nervous system of lower vertebrates can afford unexpectedly complex computations.

  3. Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men.

    Science.gov (United States)

    Roy, Tracey Ann; Blackman, Marc R; Harman, S Mitchell; Tobin, Jordan D; Schrager, Matthew; Metter, E Jeffery

    2002-08-01

    Muscle mass and strength losses during aging may be associated with declining levels of serum testosterone (T) in men. Few studies have shown a direct relationship between T and muscle mass and strength. Subjects were 262 men, aged 24-90 yr, from the Baltimore Longitudinal Study of Aging, who had T and sex hormone-binding globulin sex hormone-binding globulin (SHBG) measurements, from which the free T index (FTI) was calculated (T/SHBG) from serum samples collected longitudinally since 1963, total body fat mass and arm and leg fat-free mass (FFM) by dual-energy X-ray absorptiometry and arm and leg strength by dynanomometry. Mixed-effects models estimated T and FTI at the time of mass and strength measurements. Age, total body fat, arm and leg FFM, T, and FTI were significantly associated with concentric and eccentric strength. FTI, not T, was modestly, but directly, related to arm and leg strength after fat, arm and leg FFM, height, and age were accounted for and indirectly through body mass. FTI is a better predictor of arm and leg strength than T in aging men.

  4. Melanin-binding radiopharmaceuticals

    International Nuclear Information System (INIS)

    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

  5. Competitive protein binding assay

    International Nuclear Information System (INIS)

    Kaneko, Toshio; Oka, Hiroshi

    1975-01-01

    The measurement of cyclic GMP (cGMP) by competitive protein binding assay was described and discussed. The principle of binding assay was represented briefly. Procedures of our method by binding protein consisted of preparation of cGMP binding protein, selection of 3 H-cyclic GMP on market, and measurement procedures. In our method, binding protein was isolated from the chrysalis of silk worm. This method was discussed from the points of incubation medium, specificity of binding protein, the separation of bound cGMP from free cGMP, and treatment of tissue from which cGMP was extracted. cGMP existing in the tissue was only one tenth or one scores of cGMP, and in addition, cGMP competed with cGMP in binding with binding protein. Therefore, Murad's technique was applied to the isolation of cGMP. This method provided the measurement with sufficient accuracy; the contamination by cAMP was within several per cent. (Kanao, N.)

  6. High dose Intravenous Anti-D Immune Globulin is More Effective and Safe in Indian Paediatric Patients of Immune Thrombocytopenic Purpura.

    Science.gov (United States)

    Swain, Trupti Rekha; Jena, Rabindra Kumar; Swain, Kali Prasanna

    2016-12-01

    Immune Thrombocytopenia (ITP) is characterised by an autoimmune antibody-mediated destruction of platelets and impaired platelet production. Few controlled trials exist to guide management of patients with ITP in Indian scenario for which patients require an individualized approach. Anti-D (Rho (D) immune globulin) at a higher dose can prove to be a cost effective and safe alternative for Indian patients with ITP. To compare the safety and efficacy of higher dose (75μg/kg) intravenous Anti-D immune globulin against the standard dose of 50μg/kg for the management of ITP in Indian patients. One hundred and sixty four children with newly diagnosed ITP between 4-14 years were randomly selected for inclusion and were treated with 50μg/kg (standard dose) or 75μg /kg (higher dose) of Anti-D to compare the efficacy and safety of higher dose intravenous anti-D immune globulin. Efficacy of Anti-D was measured in terms of rate of response and median time to response for increase in platelet counts. Any adverse event was noted. A decrease in haemoglobin concentration suggested accompanying haemolysis. Seventy one out of 84 patients treated with Anti-D at 75μg/kg produced complete response (85%) with median time of response being 2.5 days. On the contrary, 45 patients (70%) patients treated with 50μg/kg had complete response. However, there was no significant increase in haemolysis with higher dose. A significant correlation was found between dose and peak increase in platelet count measured at 7 th day following administration. However, there was no relationship between the decrease in haemoglobin and the dose given, or between the increase in platelet count and fall in haemoglobin. A 75μg/kg dose of Anti-D is more effective with acceptable side effect in comparison to 50μg dose for treatment of newly diagnosed Indian patients of ITP.

  7. Corticosterone binding to tissues of adrenalectomized lean and obese Zucker rats.

    Science.gov (United States)

    Grasa, M M; Cabot, C; Balada, F; Virgili, J; Sanchis, D; Monserrat, C; Fernández-López, J A; Remesar, X; Alemany, M

    1998-12-01

    The binding of corticosterone, dexamethasone and aldosterone was investigated in plasma and in homogenates of liver, kidney, brain, brown adipose tissue and visceral (periovaric) and subcutaneous white adipose tissues of Zucker lean and obese rats: intact controls, adrenalectomized and sham-operated. Corticosterone-binding globulin (CBG) accounted for most of the binding, whereas that of glucocorticoid and mineralocorticoid receptors was much lower. Plasma corticosterone levels increased in sham-operated and obviously decreased in the adrenalectomized animals. Sham-operated and adrenalectomized lean rats showed decreased plasma CBG; in the obese, CBG levels were lower than in controls and were not affected by either surgery. No variation with obesity or surgery was observed either in dexamethasone or aldosterone binding, the latter being practically zero in most samples. When expressed per unit of tissue protein, CBG activity was maximal in adipose tissues, with lowest values in brain and liver. In lean rats, tissue CBG activity decreased with either surgical treatment; no changes were observed in the obese, which also had lower CBG tissue levels. The relative lack of changes in CBG of obese rats suggests that they have lost -- at least in part -- the ability to counter-modulate the changes in glucocorticoid levels through CBG modulation, thus relying only on the control of corticosterone levels. This interpretation agrees with the postulated role of CBG modulating the availability of glucocorticoids to target cells.

  8. Simultaneous passive and active immunization against hepatitis B: noninterference of hepatitis B immune globulin with the anti-HBs response to reduced doses of heat-inactivated hepatitis B vaccine

    NARCIS (Netherlands)

    Lelie, P. N.; Reesink, H. W.; Grijm, R.; de Jong-van Manen, S. T.; Reerink-Brongers, E. E.

    1986-01-01

    The effect of simultaneous administration of hepatitis B immune globulin on the antibody response to a low dose of heat-inactivated hepatitis B vaccine was investigated in 175 health care workers. Subjects were divided into four groups: Groups I and II received 3 monthly injections of a reduced dose

  9. Effect of ionizing whole-body irradiation on the primary and secondary antibody reaction of cows to injection of human gamma globulin

    International Nuclear Information System (INIS)

    Koch, F.; Buchholz, I.; Mehlhorn, G.

    1989-01-01

    In 3 experiments 29 cows were exposed to whole-body irradiation, using 9 MeV X-rays of a linear accelerator, with doses of 1.50 and 2.00 Gy or 60 Co gamma rays with a dose of 2.75 Gy, as a midline dose. 2 weeks prior to irradiation the first immunization was applied using human gamma globulin. 4 or 5 weeks after irradiation a second immunization was carried out. The antibody titres were investigated. The irradiation failed to affect the antibody titres after the first immunization. After the second immunization the antibody titres of the irradiated animals remained diminished significantly (α = 0.05). This has been attributed to a damage of the memory cell pool. (author)

  10. 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

  11. Ovarian ultrasound and ovarian and adrenal hormones before and after treatment for hyperthyroidism.

    Science.gov (United States)

    Skjöldebrand Sparre, L; Kollind, M; Carlström, K

    2002-01-01

    To relate thyroid, steroid and pituitary hormones to ovarian ultrasonographic findings in hyperthyroid patients before and during treatment. Ultrasonography of the ovaries and serum hormone determination by immunoassay were performed before and during thiamazole therapy in 18 women of fertile age treated for hyperthyroidism at the Danderyd Hospital from 1996 to 1998. When hyperthyreotic, the patients had elevated serum levels of sex hormone-binding globulin (SHBG) and subnormal values of cortisol, free testosterone (fT) and dehydroepiandrosterone (DHEA). In the euthyreotic state following treatment, endocrine variables were normalized. Patients with a short duration of the disease had higher pretreatment levels of free thyroxine (fT4), SHBG and testosterone and lower corticosteroid binding globulin (CBG) and cortisol levels compared to patients with a long duration of the disease. The pretreatment ultrasonographic picture was abnormal in 16 of 18 patients. Of the 8 patients who were examined by ultrasonography after 3 months of treatment, all but 1 showed a normal picture. Samples from patients showing an abnormal ultrasonographic picture had significantly higher fT4 and lower free testosterone (fT) values than samples from patients with a normal ultrasonographic picture. Ultrasonographic findings showing a multicystic/multifollicular picture, resembling polycystic ovaries (PCO), in hyperthyroidism may be related to direct effects of thyroid hormones on the ovaries and/or altered intraovarian androgen environment due to elevated SHBG levels. It is highly recommended to assess the thyroid status in patients with multicystic/multifollicular ovaries/PCO. Copyright 2002 S. Karger AG, Basel

  12. Early follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee use.

    Science.gov (United States)

    Lucero, J; Harlow, B L; Barbieri, R L; Sluss, P; Cramer, D W

    2001-10-01

    To examine the effects of alcohol, caffeine, and tobacco use on early follicular phase FSH, LH, E2, and sex hormone-binding globulin (SHBG). Cross-sectional study. Academic medical center. Four hundred ninety-eight women selected from the general population, ages 36-45, who were not currently pregnant, breast feeding, or using exogenous hormones. A general questionnaire assessing demography, anthropometry, and smoking habits and a standardized dietary questionnaire assessing food and beverage frequencies, including sources of alcohol and caffeine. FSH, LH, E2, and SHBG levels measured during the early follicular phase of the menstrual cycle. Significant associations observed in a univariate analysis included age > or =40 and current smoking associated with higher FSH; higher body mass index (BMI) associated with lower SHBG levels; and daily alcohol use, cholesterol consumption greater than the median, and coffee use >1 cup/d associated with higher E2 levels. In a multivariate model, total caffeine use was significantly associated with E2 levels after adjustment for age, BMI, total calories, current smoking, alcohol, cholesterol consumption, and day of sampling. Early follicular phase E2 increased from 28.2 pg/mL for women consuming or =500 mg of caffeine per day, about a 70% increase. Coffee consumption and total caffeine use may increase early follicular phase E2 levels independent of related habits of alcohol or tobacco use.

  13. Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies

    Science.gov (United States)

    Key, T J; Appleby, P N; Reeves, G K; Roddam, A W; Helzlsouer, K J; Alberg, A J; Rollison, D E; Dorgan, J F; Brinton, L A; Overvad, K; Kaaks, R; Trichopoulou, A; Clavel-Chapelon, F; Panico, S; Duell, E J; Peeters, P H M; Rinaldi, S; Fentiman, I S; Dowsett, M; Manjer, J; Lenner, P; Hallmans, G; Baglietto, L; English, D R; Giles, G G; Hopper, J L; Severi, G; Morris, H A; Hankinson, S E; Tworoger, S S; Koenig, K; Zeleniuch-Jacquotte, A; Arslan, A A; Toniolo, P; Shore, R E; Krogh, V; Micheli, A; Berrino, F; Barrett-Connor, E; Laughlin, G A; Kabuto, M; Akiba, S; Stevens, R G; Neriishi, K; Land, C E; Cauley, J A; Lui, Li Yung; Cummings, Steven R; Gunter, M J; Rohan, T E; Strickler, H D

    2011-01-01

    Background: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. Methods: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. Results: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. Conclusion: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. PMID:21772329

  14. Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries.

    Science.gov (United States)

    Anttila, L; Koskinen, P; Kaihola, H L; Erkkola, R; Irjala, K; Ruutiainen, K

    1992-10-01

    To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

  15. Hormonal profiles behind the heart of a man.

    Science.gov (United States)

    Sarkar, Narendra Nath

    2009-01-01

    This study focuses on the role of sex steroids on the libido, sexual life, emotional and physiological heart of men of all ages. Sex steroids play a significant role throughout a man's life, with a gradual decline in old age. The foetal testis secretes testosterone and dehydroepiandrosterone at about nine weeks gestation. At puberty, testosterone increases dramatically in boys. Changes in weight and height of boys across this period are associated with increasing testosterone concentration and sex hormone binding globulin (SHBG). Romantic thoughts, fantasy, and sexual pleasure-seeking behaviour in adolescents are associated with exposure to high androgens secretion. Thus, the libido and sexual life of a man is initiated and maintained by testosterone and SHBG. Lower testosterone levels are associated with erectile dysfunction among other risk factors: diabetes, hypertension, heart disease, psychological stress and obesity. Men with proven coronary atherosclerosis have lower levels of testosterone and SHBG, which have negative correlation with very low-density lipoprotein, triglycerides, body mass index and body fat mass. These are some of the risk factors for cardiovascular diseases. Thus, in men, endogenous sex steroids impart beneficial effects on the heart. How exactly endogenous sex steroids act on the heart is not clear. Further study is needed to understand the interaction between endogenous sex steroids, higher centers in the brain and the heart of a man.

  16. Obesity as a protective factor for postmenopausal osteoporosis.

    Science.gov (United States)

    Albala, C; Yáñez, M; Devoto, E; Sostin, C; Zeballos, L; Santos, J L

    1996-11-01

    Obesity is considered a protective factor for osteoporosis improving bone mass and maintaining higher levels of estrogen during menopause. To determine the association of obesity with bone mineral density (BMD), and its relationship with sex hormone levels. A case-control study in Caucasian obese and non obese postmenopausal women. 113 obese and 50 non-obese postmenopausal women. BMD (dual-photon X-ray absorptiometry) at cervical femur. Ward's triangle, proximal radius and lumbar spine. Plasma levels of glucose, insulin, total estrogen, follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHA-S) and testosterone. Mean BMD at femoral sites were significantly higher in obese women (femoral neck: 0.849 +/- 0.124 g/cm2 vs 0.753 +/- 0.095 g/cm2, P obese women and 0.849 +/- 0.137 g/cm2 in non obese, P obese women was observed. Although total estrogen were similar in both groups, in obese women, SHBG was lower (68.6 +/- 26.84 nmol/l vs. 85.1 +/- 31.18 nmol/l, P obese (77.2 +/- 50.4 Ul/ml vs. 49.4 +/- 24.1 Ul/ml, P obese women and suggest that obesity exerts protection due to a decreased SHBG thus increasing free sex steroids. Besides, hyperinsulinemia may produce a decline in the production of IGFBG-1, leading to an increase of IGF-1, that may stimulate the proliferation of osteoblasts.

  17. Interictal hyposexuality in male patients with epilepsy

    Directory of Open Access Journals (Sweden)

    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.

  18. Metformin influence on hormone levels at birth, in PCOS mothers and their newborns.

    Science.gov (United States)

    Carlsen, S M; Vanky, E

    2010-03-01

    Polycystic ovary syndrome (PCOS) tends to run in families and excess intrauterine androgen exposure has been suggested as one possible cause of PCOS. We wanted to study the relationship between maternal and offspring sex hormone levels and the possible effects of metformin treatment in PCOS pregnancies. We performed a post hoc analysis of a trial in which 40 pregnant women with PCOS were randomized in the first trimester, to use either metformin 850 mg twice daily or placebo until delivery. Maternal venous blood and umbilical arterial and venous blood samples were collected at delivery. Outcome measures were levels of androgens, estrogens and sex hormone binding globulin (SHBG). (i) In newborns, SHBG levels were higher in the metformin group. All other hormones, both in mothers and offspring, were unaffected by metformin treatment. (ii) Mothers, who gave birth to boys, had higher estrone and estradiol levels compared with those who gave birth to girls. (iii) Male newborns had higher levels of testosterone, androstanediol glucuronide and estradiol compared with females. (iv) Positive correlations were found between maternal and newborn levels of androstenedione, dihydrotestosterone and estradiol. Intrauterine metformin exposure seems to result in elevated SHBG levels in newborns. However, at birth, maternal and newborn androgen and estrogen levels are unaffected by metformin use in pregnancy. Although androgen and estrogen levels are higher in male newborns compared with females, maternal and newborn androgen and estrogen levels are highly correlated at birth.

  19. 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....

  20. Low capacity of erythrocytes to bind with immune complexes via C3b receptor in patients with systemic lupus erythematosus: correlation with pathological proteinuria

    International Nuclear Information System (INIS)

    Nojima, Y.; Terai, C.; Minota, S.; Takano, K.; Miyakawa, Y.; Takaku, F.

    1985-01-01

    Erythrocytes from 51 patients with systemic lupus erythematosus and 75 controls were tested for the capacity to bind aggregated human gamma-globulin labeled with radioiodine in the presence of complement. Both in patients and controls, a trimodal distribution of binding capacity was observed. Low (less than 9% of the added radioactivity), intermediate (9-17%), and high binding (more than 17%) were observed in 13, 58, and 29% in controls and in 49, 43 and 8% in lupus patients. The low binding capacity of erythrocytes persisted even after patients entered remission following steroid therapy. A genetic control of binding capacity was supported by familial surveys. Prevalence of pathological proteinuria was significantly higher in patients with low binding capacity than those with intermediate or high binding capacity (16/25 vs 7/26, P less than 0.01). These results indicate that an impaired physiological disposal of immune complexes via the erythrocyte C3b receptor in lupus patients may contribute to the development of renal involvement

  1. Interactions of 16{alpha}-[{sup 18}F]-fluoroestradiol (FES) with sex steroid binding protein (SBP)

    Energy Technology Data Exchange (ETDEWEB)

    Tewson, T.J. E-mail: ttewson@u.washington.edu; Mankoff, D.A.; Peterson, L.M.; Woo, I.; Petra, P

    1999-11-01

    Fluorine-18 16{alpha}-Fluoroestradiol ([{sup 18}F]- FES) is a positron-emitting tracer for the estrogen receptor that is used for positron emission tomography (PET) studies of tumor tissues rich in the estrogen receptor. The role of the sex steroid binding protein (SBP or SHBG) in the transport of the [{sup 18}F]-FES to the estrogen-receptor-rich tissue in breast cancer patients in vivo was investigated. To determine the extent to which [{sup 18}F]-FES is bound to SBP in the blood, we performed a series of studies using blood samples obtained from patients undergoing [{sup 18}F]-FES PET scans. The binding of [{sup 18}F]-FES to the SBP was measured using a simple protein precipitation assay. The binding of [{sup 18}F]-FES metabolites to SBP was also measured. These measurements showed that the tracer was distributed between albumin and SBP, and the binding capacity of SBP was sufficient to ensure that the protein was not saturated when the tracer was fully mixed with the plasma; however, local saturation of SBP may occur when [{sup 18}F]-FES is administered intravenously. Typically about 45% of [{sup 18}F]-FES in circulating plasma was bound to SBP, but this fraction was dependent on the concentration of SBP in plasma. The transfer of the tracer between the two proteins was rapid, complete in less than 20 s at 0 deg. C, suggesting that the equilibrium was maintained under most circumstances and that local saturation resolved quickly when blood from the injection site entered the central circulation. These data suggest that SBP binding of [{sup 18}F]-FES is significant and will affect the input function of the tracer for any model that is used for the quantitative evaluation of [{sup 18}F]-FES uptake in PET studies. Estimates of equilibrium binding in blood samples are sufficient to characterize [{sup 18}F]-FES binding to SBP in the circulation.

  2. Preparation of steroid radioligands for ultrafiltration assays by a solid-phase transport globulin method using concanavalin A-Sepharose

    International Nuclear Information System (INIS)

    Hiramatsu, R.; Nisula, B.C.

    1985-01-01

    Concanavalin A-Sepharose (Con A-Sepharose) was applied to separate non-protein-bound and albumin-bound radioactive impurities from steroid radioligands. Con A-Sepharose gel, plasma, and steroid radioligand were mixed, incubated, and then washed with buffer. This method was compared with an affinity diafiltration method which separates non-protein-bound radioactive impurities with a filter membrane. 3 H-Water and 3 H-estrone sulfate, chosen to serve as molecules representative of non-protein-bound and albumin-bound impurities, were removed quite effectively by the Con A-Sepharose method, while 85% of 3 H-estrone sulfate could not be removed by the diafiltration method. Plasma unbound cortisol (F) and testosterone (T) values determined by ultrafiltration using 3 H-F and 3 H-T prepared by the Con A-Sepharose method were significantly lower than those determined using the radioligands unprocessed or prepared by the diafiltration method. The whole procedure of the Con A-Sepharose method takes only 3-4 hours. This method is a simple, rapid, and effective technique for preparation of steroid radioligands for plasma protein binding studies

  3. A simple and rapid Hepatitis A Virus (HAV titration assay based on antibiotic resistance of infected cells: evaluation of the HAV neutralization potency of human immune globulin preparations

    Directory of Open Access Journals (Sweden)

    Kaplan Gerardo G

    2008-12-01

    Full Text Available Abstract Background Hepatitis A virus (HAV, the causative agent of acute hepatitis in humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV titrations are laborious and time-consuming because the virus in general does not cause cytopathic effect and is detected by immunochemical or molecular probes. Simple HAV titration assays could be developed using currently available viral construct containing selectable markers. Results We developed an antibiotic resistance titration assay (ARTA based on the infection of human hepatoma cells with a wild type HAV construct containing a blasticidin (Bsd resistance gene. Human hepatoma cells infected with the HAV-Bsd construct survived selection with 2 μg/ml of blasticidin whereas uninfected cells died within a few days. At 8 days postinfection, the color of the pH indicator phenol red in cell culture media correlated with the presence of HAV-Bsd-infected blasticidin-resistant cells: an orange-to-yellow color indicated the presence of growing cells whereas a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were determined by an endpoint dilution assay based on the color of the cell culture medium scoring orange-to-yellow wells as positive and pink-to-purple wells as negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV neutralization potency of two commercially available human immune globulin (IG preparations and a WHO International Standard for anti-HAV. The three IG preparations contained comparable levels of anti-HAV antibodies that neutralized approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in the absence of blasticidin by an endpoint dilution ELISA at 2 weeks postinfection. Conclusion The ARTA is a simple and rapid method to determine HAV titers without using HAV-specific probes. We determined the HAV neutralization potency of human IG preparations in 8 days by ARTA compared to the 14 days required by the

  4. Prognostic value of pretreatment albumin–globulin ratio in predicting long-term mortality in gastric cancer patients who underwent D2 resection

    Directory of Open Access Journals (Sweden)

    Liu J

    2017-04-01

    Full Text Available Jianjun Liu,1,2,* Shangxiang Chen,1,2,* Qirong Geng,1,3 Xuechao Liu,1,2 Pengfei Kong,1,2 Youqing Zhan,1,2 Dazhi Xu1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 2Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 3Department of Hematology Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Several studies have highlighted the prognostic value of the albumin–globulin ratio (AGR in various kinds of cancers. Our study was designed to assess whether AGR is associated with the prognosis of gastric cancer patients. Patients and methods: A total of 507 gastric cancer patients between 2005 and 2012 were included. The AGR was defined as the ratio of serum albumin to nonalbumin and calculated by the equation: albumin/(total protein - albumin. Furthermore, AGR was divided into two groups (low and high using the X-tile software. Survival analysis stratified by AGR groups was performed. Results: The mean survival time for each group was 36.62 months (95% CI: 33.92–39.32 for the low AGR group and 48.95 months (95% CI: 41.93–55.96, P=0.003 for the high AGR group. Patients in the high group (AGR ≥1.93 had a significantly lower 5-year mortality in comparison with the low group (AGR <1.93 (52.4% vs 78.5%, P=0.003. The high AGR group showed obviously better overall survival than the low AGR group according to Kaplan–Meier curves (P=0.003. Multivariate analysis showed that AGR was an independent predictive factor of prognosis in gastric patients. Conclusion: Pretreatment AGR is a significant and independent predictive factor of prognosis. Keywords: gastric cancer, survival, inflammation, albumin–globulin ratio

  5. 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.

  6. 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.

  7. 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

  8. Synchronous fluorescence based biosensor for albumin determination by cooperative binding of fluorescence probe in a supra-biomolecular host-protein assembly.

    Science.gov (United States)

    Patra, Digambara

    2010-01-15

    A synchronous fluorescence probe based biosensor for estimation of albumin with high sensitivity and selectivity was developed. Unlike conventional fluorescence emission or excitation spectral measurements, synchronous fluorescence measurement offered exclusively a new synchronous fluorescence peak in the shorter wavelength range upon binding of chrysene with protein making it an easy identification tool for albumin determination. The cooperative binding of a fluorescence probe, chrysene, in a supramolecular host-protein assembly during various albumin assessments was investigated. The presence of supramolecular host molecules such as beta-cyclodextrin, curucurbit[6]uril or curucurbit[7]uril have little influence on sensitivity or limit of detection during albumin determination but reduced dramatically interference from various coexisting metal ion quenchers/enhancers. Using the present method the limit of detection for BSA and gamma-Globulin was found to be 0.005 microM which is more sensitive than reported values. Copyright 2009 Elsevier B.V. All rights reserved.

  9. Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial

    OpenAIRE

    Locatelli, Franco; Bernardo, Maria Ester; Bertaina, Alice; Rognoni, Carla; Comoli, Patrizia; Rovelli, Attilio; Pession, Andrea; Fagioli, Franca; Favre, Claudio; Lanino, Edoardo; Giorgiani, Giovanna; Merli, Pietro; Pagliara, Daria; Prete, Arcangelo; Zecca, Marco

    2017-01-01

    Background Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immunemediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II–IV acute graft-versus-host disease (GVHD). Methods We conducted a multicentre, randomised, open-label, p...

  10. 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. Copyright© Ferrata Storti Foundation.

  11. Meta-analysis on the Safety and Efficacy of the Reperfusion Use of a Single High Dose of Anti-T-Lymphocyte Globulin Fresenius in Kidney Transplantation.

    Science.gov (United States)

    Du, X; Wang, W; Sun, Z-J; Su, L L; Zhang, X-D

    2016-01-01

    The aim of this study was to evaluate the effects of a single high dose of the anti-T-lymphocyte globulin Fresenius (ATG-F), given before kidney transplantation, on the prevention of acute rejection response and infections and on the survival rate of the renal graft and patient. Databases including PubMed, Embase, and the Cochrane Library were searched to identify randomized controlled trials relevant to studying the presurgical use of a single high dose of ATG-F. Five RCTs that included 346 patients were selected. The meta-analysis suggested that the application of ATG-F reduced the postsurgical acute rejection reaction incidence compared to that of the control group (relative risk = 0.50, 95% confidence interval = 0.35-0.71, P = .0001). However, the application of ATG-F exhibited no significant effect on the incidence of urinary tract infection, cytomegalovirus infection, and delayed graft function. Furthermore, the one-year patient survival rate and kidney graft survival rate were not affected. The meta-analysis suggested that the reperfusion use of a single high dose (9 mg/kg) of ATG-F could effectively reduce the incidence of postsurgical acute rejection response without affecting the occurrence of infections, the survival rates of kidney grafts and patients, or the incidence of delayed graft function. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Anti-thymocyte globulin could improve the outcome of allogeneic hematopoietic stem cell transplantation in patients with highly aggressive T-cell tumors

    International Nuclear Information System (INIS)

    Yang, J; Cai, Y; Jiang, J L; Wan, L P; Yan, S K; Wang, C

    2015-01-01

    The early experiment result in our hospital showed that anti-thymocyte globulin (ATG) inhibited the proliferation of lymphoid tumor cells in the T-cell tumors. We used the ATG as the part of the conditioning regimen and to evaluate the long-term anti-leukemia effect, the safety and complication in the patients with highly aggressive T-cell lymphomas. Twenty-three patients were enrolled into this study. At the time of transplant, six patients reached first or subsequent complete response, three patients had a partial remission and 14 patients had relapsed or primary refractory disease. The conditioning regimen consisted of ATG, total body irradiation, toposide and cyclophosphamide. The complete remission rate after transplant was 95.7%. At a median follow-up time of 25 months, 16 (69.6%) patients are alive and free from diseases, including nine patients in refractory and progressive disease. Seven patients died after transplant, five from relapse and two from treatment-related complications. The incidence of grades II–IV acute graft-vs-host disease (GvHD) was 39.1%. The maximum cumulative incidence of chronic GvHD was 30%. The most frequent and severe conditioning-related toxicities observed in 8 out of 23 patients were grades III/IV infections during cytopenia. Thus, ATG-based conditioning is a feasible and effective alternative for patients with highly aggressive T-cell tumors

  13. Disparate rates of acute rejection and donor-specific antibodies among high-immunologic risk renal transplant subgroups receiving antithymocyte globulin induction.

    Science.gov (United States)

    Patel, Samir J; Suki, Wadi N; Loucks-DeVos, Jennifer; Graviss, Edward A; Nguyen, Duc T; Knight, Richard J; Kuten, Samantha A; Moore, Linda W; Teeter, Larry D; Gaber, Lillian W; Gaber, A Osama

    2016-08-01

    Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups. © 2016 Steunstichting ESOT.

  14. Incidence and Pattern of Graft-versus-Host Disease in Patients Undergoing Allogeneic Transplantation after Nonmyeloablative Conditioning with Total Lymphoid Irradiation and Antithymocyte Globulin

    Directory of Open Access Journals (Sweden)

    Lauren Veltri

    2013-01-01

    Full Text Available Nonmyeloablative (NMA conditioning with total lymphoid irradiation and antithymocyte globulin (TLI/ATG has been shown to protect against acute graft-versus-host disease (GVHD. We report here our institutional experience with allogeneic transplantation following NMA conditioning with TLI/ATG (. GVHD prophylaxis consisted of a combination of a calcineurin inhibitor and mycophenolate mofetil. Median patient age was 59 years. The median followup of surviving patients is 545 days. One patient experienced primary graft rejection. The median time to neutrophil engraftment was 18 days and platelet engraftment was 9.5 days. The cumulative incidence (CI of grade II–IV acute GVHD at day +100 was 28.6% and 38.1% at day +180. The CI for grade III-IV acute GVHD was 28.6% at day +180. CI of chronic GVHD was 45.2% at 1 year. The CI of disease relapse was 9.5% at 1 year. The rate of nonrelapse mortality (NRM was 0% at day +100 and only 9.5% at 1 year. The overall and progression free survival at 1 year was 81% and 80.4%, respectively. Our limited, retrospective data show encouraging relapse and NRM rates with TLI/ATG-based NMA conditioning, but with higher than previously reported rates of acute and chronic GVHD, underscoring the need for novel strategies designed to effectively prevent GVHD.

  15. Stable long-term pulmonary function after fludarabine, antithymocyte globulin and i.v. BU for reduced-intensity conditioning allogeneic SCT.

    Science.gov (United States)

    Dirou, S; Malard, F; Chambellan, A; Chevallier, P; Germaud, P; Guillaume, T; Delaunay, J; Moreau, P; Delasalle, B; Lemarchand, P; Mohty, M

    2014-05-01

    Lung function decline is a well-recognized complication following allogeneic SCT (allo-SCT). Reduced-intensity conditioning (RIC) and in vivo T-cell depletion by administration of antithymocyte globulin (ATG) may have a protective role in the occurrence of late pulmonary complications. This retrospective study reported the evolution of lung function parameters within the first 2 years after allo-SCT in a population receiving the same RIC regimen that included fludarabine and i.v. BU in combination with low-dose ATG. The median follow-up was 35.2 months. With a median age of 59 years at the time of transplant, at 2 years, the cumulative incidences of non-relapse mortality was as low as 9.7%. The cumulative incidence of relapse was 33%. At 2 years, the cumulative incidences of extensive chronic GVHD (cGVHD) and of pulmonary cGVHD were 23.1% and 1.9%, respectively. The cumulative incidences of airflow obstruction and restrictive pattern were 3.8% and 9.6%, respectively. Moreover, forced expiratory volume (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio remained stable from baseline up to 2 years post transplantation (P=0.26, P=0.27 and P=0.07, respectively). These results correspond favorably with the results obtained with other RIC regimens not incorporating ATG, and suggest that ATG may have a protective pulmonary role after allo-SCT.

  16. Possible cleavage sites of glutelin partial degradation confirmed by immunological analysis in globulin-less mutants of rice (Oryza sativa L.).

    Science.gov (United States)

    Khan, Nadar; Yamaguchi, Satoru; Katsube-Tanaka, Tomoyuki

    2017-10-01

    Proteolytic cleavage or partial degradation of proteins is one of the important post-translational modifications for various biological processes, but it is difficult to analyze. Previously, we demonstrated that some subunits of the major rice (Oryza sativa L.) seed storage protein glutelin are partially degraded to produce newly identified polypeptides X1-X5 in mutants in which another major seed storage protein globulin is absent. In this study, the new polypeptides X3 and X4/X5 were immunologically confirmed to be derived from GluA3 and GluA1/GluA2 subunits, respectively. Additionally, the new polypeptides X1 and X2 were at least in part the α polypeptides of the GluB4 subunit partially degraded at the C-terminus. Simulated 2D-PAGE migration patterns of intact and partially degraded α polypeptides based on the calculation of their MWs and pIs enabled us to narrow or predict the possible locations of cleavage sites. The predicted cleavage sites were also verified by the comparison of 2D-PAGE patterns between seed-extracted and E. coli-expressed proteins of the intact and truncated α polypeptides. The results and methodologies demonstrated here would be useful for analyses of partial degradation of proteins and the structure-function relationships of rice seed protein bodies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. ROL' POLOVYKh GORMONOV V REGULYaTsII KOSTNOGO OBMENA i mineral'noy plotnostikostnoy tkani u muzhchin v pozdnie sroki posle allotransplantatsii trupnoy pochki

    Directory of Open Access Journals (Sweden)

    I A PRONChENKO

    2006-08-01

    Full Text Available Lumbal spine and hip bone mineral density (BMD, bone turnover markers [bone alkaline phosphatase (bALP, osteocalcin (OC, aminoterminal procollagen I propeptide, bone acid phosphatase (bACP, ß-crosslaps (CTX], sex hormones [testosterone, estradiol (E2, sex hormone-binding globulin (SHBG, free androgen index (FAI, free estrogen index (FEI], parathyroid hormone (PTH, osteoprotegerin (OPG and insulin-like growth factor-1 (IGF-1] were determined in 39 men in age 42±10 years (33 with well renal function and 6 - with renal failure (RF 44±26 months following KT receiving triple immunosuppressive therapy (CysA, prednisolone and azathioprine. Increased CTX, bACP, OC and decreased bALP so as BMD were associated in men following KT with low testosterone, SHBG and IGF-1 and high E2, OPG and PTH. There was more degree of bone turnover disturbances, decreased BMD, PTH hypersecretion and low FAI in RF. There were significant positive relationships between serum testosterone and E2, FEI and FAI, bALP and E2, bALP and FEI, femur BMD and FAI, femur BMD and FEI, OPG and E2, IGF-1 and PTH. There were significant inverse correlations between serum CTX and FAI, CTX and FEI, hip (spine BMD and SHBG, hip (spine BMD and PTH so as between PTH and FAI, PTH and FEI. So bone turnover disturbances, hip BMD losses and PTH hypersecretion in men at late time following KT associated with sex hormone deficiency. Predictor of high bone turnover and as vertebral as femur bone losses after KT besides PTH hypersecretion was serum SHBG. Decreased IGF-1 was the reason of bone forming suppression and possibly was following cyclosporine hepatotoxicity. OPG increasing was associated partly with high estradiol and was compensatory to attenuation of bone resorption and bone losses.

  18. Reproductive Hormones and Subclinical Cardiovascular Disease in Midlife Women.

    Science.gov (United States)

    Thurston, Rebecca C; Bhasin, Shalender; Chang, Yuefang; Barinas Mitchell, Emma; Matthews, Karen A; Jasuja, Ravi; Santoro, Nanette

    2018-05-18

    Reproductive hormones are understood to be important to the pathophysiology of cardiovascular disease (CVD) in women. However, standard estradiol (E2) and testosterone (T) assays lack sensitivity at the levels of postmenopausal women. Investigate relations of mass spectrometry-assessed estrone (E1), estradiol (E2), and testosterone (T), and sex hormone binding globulin (SHBG) and subclinical CVD in women. 304 peri- and postmenopausal women, aged 40-60 years, and free of clinical CVD underwent subclinical CVD measurements. E1, E2, and T were assayed using liquid chromatography-tandem mass spectrometry; Free T (FT) was estimated using ensemble allostery models. Associations between hormones and outcomes were analyzed using regression models adjusting for CVD risk factors. Carotid artery intima media thickness (IMT), inter-adventitial diameter (IAD), plaque; brachial flow mediated dilation (FMD). Higher E1 was related to higher FMD [b(SE)=.77(.37), p=.04], indicating better endothelial function. Higher E2 was related to lower IAD [b(SE)=-.07(.02), p=.004], indicating less carotid remodeling. Higher SHBG was related to higher FMD [b(SE)=1.31(.40), p=.001], yet higher IAD [b(SE)=.15(.06), p=.02] and carotid plaque [OR (95%CI)=1.84(1.16-2.91), p=.009]. Higher FT was associated with lower FMD [b(SE)=-1.58(.52), p=.003], yet lower IAD [b(SE)=-.19(.08), p=.01] and carotid plaque [OR(95%CI)=.49(.28-.88), p=.02]. Thus, higher SHBG and lower FT was associated with better endothelial function, yet greater carotid remodeling and plaque. Endogenous E1 levels were related to endothelial function and E2 to vascular remodeling, suggesting distinct roles of these estrogens. SHBG and free testosterone have a complex role and depend on the vessel under study.

  19. Effects of experimentally induced mild hyperthyroidism on growth hormone and insulin secretion and sex steroid levels in healthy young men.

    Science.gov (United States)

    Lovejoy, J C; Smith, S R; Bray, G A; Veldhuis, J D; Rood, J C; Tulley, R

    1997-12-01

    Although triiodothyronine (T3) exerts major regulatory actions in both animals and humans, most clinical studies of T3 administration have been relatively short-term. The present study examined the effects of more than 2 months (63 days) of low-dose T3 treatment on overnight pulsatile growth hormone (GH) secretion, short-term insulin secretion, and of sex steroid levels in seven healthy, lean men studied at an inpatient metabolic unit. At baseline, there were strong correlations between sex hormone-binding globulin (SHBG) and several measures of GH production, including total GH production (r = .99), GH interburst interval (r = -.75), and GH mass (r = .82). SHBG was also inversely correlated with basal insulin secretion (r = -.74). There was a 42% increase in serum levels of total testosterone (18.5 +/- 1.3 to 26.3 +/- 1.8 nmol/L, P = .005) and a 150% increase in SHBG (18.0 +/- 2.2 to 44.9 +/- 7.0 nmol/L, P = .008) following T3 treatment. Estradiol and free testosterone levels were unchanged by treatment, although free testosterone decreased from 142.8 +/- 18.4 to 137.3 +/- 19.5 pmol/L. T3 treatment significantly reduced the GH interburst interval (P secretion. There were no statistically significant effects of T3 treatment on insulin secretion, although insulin peak amplitude, mass secreted per burst, and total production all decreased. We conclude that experimentally induced T3 excess in healthy men produces significant and sustained changes in sex hormone levels and GH secretion. Furthermore, there are strong associations between SHBG and both GH and insulin secretion independent of thyroid hormone excess that require additional study.

  20. 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.

  1. Optical Binding of Nanowires

    Czech Academy of Sciences Publication Activity Database

    Simpson, Stephen Hugh; Zemánek, Pavel; Marago, O.M.; Jones, P.H.; Hanna, S.

    2017-01-01

    Roč. 17, č. 6 (2017), s. 3485-3492 ISSN 1530-6984 R&D Projects: GA ČR GB14-36681G Grant - others:AV ČR(CZ) CNR-16-12 Program:Bilaterální spolupráce Institutional support: RVO:68081731 Keywords : optical binding nanowires * Brownian motion * self-organization * non-equilibrium thermodynamics * non-equilibrium steady state * spin-orbit coupling * emergent phenomena Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: Optics (including laser optics and quantum optics) Impact factor: 12.712, year: 2016

  2. Estimated protective effectiveness of intramuscular immune serum globulin post-exposure prophylaxis during a measles outbreak in British Columbia, Canada, 2014.

    Science.gov (United States)

    Bigham, Mark; Murti, Michelle; Fung, Christina; Hemming, Felicity; Loadman, Susan; Stam, Robert; Van Buynder, Paul; Lem, Marcus

    2017-05-09

    Intramuscular Immune Serum Globulin (IM ISG) is recommended as post-measles exposure prophylaxis (PEP) when administered within 6days of initial exposure, with variable effectiveness in preventing measles disease. Effectiveness of IM ISG PEP in preventing clinical measles was assessed during a 2014 measles outbreak among a religious-affiliated community in British Columbia, Canada. Fifty-five self-reporting measles susceptible contacts were offered exclusively IM ISG PEP within an eligibility period best surmised to be within 6days of initial measles case exposure. Clinical outcome of IM ISG PEP recipients was determined by selective active surveillance and case self-reporting. IM ISG PEP failure was defined as onset of a measles-like rash 8-21days post-IM ISG PEP. Post-IM ISG PEP measles IgG antibody level was tested in 8 recipients. Factors associated with measles disease were analyzed. Seventeen of 55 IM ISG PEP recipients developed clinically consistent measles in the following 8-21days, corresponding to an estimated crude protective effectiveness of 69%. In school aged children 5-18years, among whom potential exposure intensity and immune status confounders were considered less likely, estimated IM ISG PEP protective effectiveness was 50%. Age effectiveness against measles disease within 8-21days post-ISG administration was 69%. Accuracy of this estimated protective effectiveness is vulnerable to assumptions and uncertainties in ascertaining exposure details and pre-exposure immune status. Increasing the Canadian recommended measles IM ISG PEP dose from 0.25 to 0.5ml/kg (up to 15ml maximum volume) may increase protective effectiveness. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Horse versus rabbit antithymocyte globulin in immunosuppressive therapy of treatment-naïve aplastic anemia: a systematic review and meta-analysis.

    Science.gov (United States)

    Yang, Nan; Chen, Jinqiu; Zhang, Hui; Dai, Zhiming; Yao, Huan; Ma, Xiaorong; Bai, Ju; Zhang, Yilin; Zhang, Wanggang

    2017-12-01

    The first-line formulation of antithymocyte globulin (ATG) remains unknown. We aimed to systematically review evidence to compare the efficacy and safety profiles of different ATGs. We did a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort controlled studies comparing horse and rabbit ATG in immunosuppressive therapy of treatment-naïve aplastic anemia. We searched The Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov , and conference proceedings of American Society of Hematology and European Society for Blood and Marrow Transplantation annual meetings. The outcomes were 3-, 6-, and 12-month response; early mortality; relapse; and evolution. We pooled hazard ratios for relapse and odds ratios (ORs) for other outcomes using fixed-effect or random-effect models based on the heterogeneity. This study was registered with PROSPERO, number CRD42016036945. We included 1636 participants from three RCTs and 11 cohort controlled studies. Allocation to horse ATG increased 6-month response events by 86% compared with rabbit ATG. The benefit of horse ATG was mainly driven by increase in studies with non-Asian (OR 95% CI = 2.39 (1.54-3.69), p < 0.0001) and good partial response criterion (OR 95% CI = 2.73 (1.53-4.89), p = 0.0007). The early mortality and evolution were similar between groups. Compared with rabbit ATG, horse ATG had superior remission by 6 months and equivalent safety profiles in patients with treatment-naïve AA. Evidence for further responses beyond 6 to 12 months was limited.

  4. Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.

    Science.gov (United States)

    Lee, DaHae; Keymeulen, Bart; Hilbrands, Robert; Ling, Zhidong; Van de Velde, Ursule; Jacobs-Tulleneers-Thevissen, Daniel; Maleux, Geert; Lapauw, Bruno; Crenier, Laurent; De Block, Christophe; Mathieu, Chantal; Pipeleers, Daniel; Gillard, Pieter

    2017-09-01

    Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

  5. Unexpected suppression of anti-Fya and prevention of hemolytic disease of the fetus and newborn after administration of Rh immune globulin.

    Science.gov (United States)

    Branch, Donald R; Scofield, Terry L; Moulds, John J; Swanson, Jane L

    2011-04-01

    Rh immune globulin (RhIG) has been used successfully for many years for the antenatal suppression of anti-D in D- mothers carrying D+ babies to prevent hemolytic disease of the fetus and newborn. Although the mechanism of RhIG-induced immunosuppression remains unknown, a recent report (TRANSFUSION 2006;46:1316-22) has shown that women receiving RhIG produce elevated levels of transforming growth factor (TGF)β-1, a powerful immunosuppressant cytokine. It was suggested that induction of TGFβ-1 and immunosuppression may be independent of cognate antigen recognition by RhIG. Herein, we present a description of a mother and baby that supports this hypothesis. Red blood cells and serum were analyzed using saline-tube indirect antiglobulin test methods. RhIG (RhoGAM) was administered after each amniocentesis performed at 28, 31, and 36 weeks' gestation. A group A, D-(cde), K+, Fy(a-b+), MNs, Jk(a+b+) mother with no detectable anti-D had an anti-Fy(a) titer of 4096 before RhIG but only 256 after RhIG. Mother gave birth to a group O, D-(cde), Fy(a+b+) healthy baby boy having a weak-positive direct antiglobulin test with anti-Fy(a) eluted from his cells and the titer in the cord serum was 4. This case demonstrates the potential immunosuppressive properties of RhIG for down regulation of a possible clinically significant alloantibody, not anti-D, where no D+ antigen is in the circulation of the mother. The case illustrates the potential utility for using RhIG to modulate antibody levels in situations other than for classical suppression of anti-D production. Although the mechanism in this case is unknown, TGFβ-1-mediated or antibody-mediated immunosuppression to soluble nonparticulate antigens are possible mechanisms. © 2010 American Association of Blood Banks.

  6. Clinical and economic outcomes of rabbit antithymocyte globulin induction in adults who received kidney transplants from living unrelated donors and received cyclosporine-based immunosuppression.

    Science.gov (United States)

    Miller, James T; Collins, Curtis D; Stuckey, Linda J; Luan, Fu L; Englesbe, Michael J; Magee, John C; Park, Jeong M

    2009-10-01

    To evaluate the efficacy, safety, and costs of rabbit antithymocyte globulin (TMG) induction in patients who received kidney transplants from living unrelated donors. Retrospective cohort study. Large academic medical center. Eighty-seven patients who received kidney transplants from living unrelated donors: 40 of the recipients underwent transplantation between January 1, 2003, and December 31, 2004, and did not receive TMG induction (no induction group); 47 underwent transplantation between January 1, 2005, and June 30, 2006, and received TMG induction (induction group). All patients received cyclosporine-based immunosuppression. Biopsy-proven acute rejection, posttransplantation complications, and inpatient hospital costs for the first 12 months after transplantation were compared between groups using standard univariate statistical analyses. Induction significantly decreased the occurrence of biopsy-proven acute rejection versus no induction (2% vs 48%, pTMG treatment. Slightly elevated initial costs associated with TMG induction were offset by lower costs related to rejection treatment. Total inpatient costs for the 12 months after transplantation were comparable between the groups (no induction $66,038 vs induction $74,183, p>0.05). For the no induction versus induction groups, no significant differences in cytomegalovirus disease (5% vs 6%), malignancy (3% vs 2%), graft failures (5% vs 6%), mortality (5% vs 4%), and serum creatinine concentrations (mean +/- SD 1.4 +/- 0.3 vs 1.5 +/- 0.3 mg/dl) were observed at 12 months (p>0.05 for all comparisons). Five-day TMG induction effectively reduced the 1-year acute rejection rate without significantly increasing total inpatient costs or posttransplantation complications among recipients of kidney transplants from living unrelated donors.

  7. Radioimmunoassay of the androgen function at healthy children

    International Nuclear Information System (INIS)

    Milanov, S.; Grigorova, R.; Koparanova, O.

    1998-01-01

    The androgen function at 67 healthy children aged 1-18 years is studied. Three age groups (1-6 yrs., n=28; 7-12 yrs., n=19; 12-18 yrs., n=20) are examined. Measurements have been done of testosterone (T), Δ-4 androstenedione (Δ-4-A) and sex hormone binding globulin (SHBG) by RIA kits of the Merieux. 17-α-hydroxyprogesterone (17α-OHP), the basic precursor os the androgens, has been measured in the serum by the same RIA kits. An increase in T and Δ-4-A levels with age is observed with significantly higher levels for 12-18 year, compared to those of 1 - 6 years (p<0.02, p<0.002) and 7-12 years (p<0.001). There is reliably higher secretion of T and Δ-4-A in boys, compared to that in 12-18 year girls (p<0.01), while in groups of smaller children only a tendency has been established, probably due to the higher SD. Decrease of the SHBG levels with age has been determined. The lowest levels belong to the binding protein in boys of 12-18 (35.93 ± 8.19 nmol/l)), compared to the other boys as well as in girls in the groups of smaller children (p<0.01). SHBG correlates strong inversely with the levels of T and (Δ-4-A in the 12-18 year boys (8.05 ± 4.4 nmol/l; 19.9 ± 5.7 nmol/l). Probably the higher levels of the two androgens determine the decrease to the binding capacity of the SHBG between 7 and 18 age during sexual development in boys. Reliable difference between the levels of 17α OHP in the smaller groups (1 month - 1 yrs.; 7 - 12 yrs.), compared to the group od 12 - 17 yrs. (p<0.01) have been found. The present study determines referent ranges of the serum levels of T, Δ-4-A, SHBG and 17α OHP in healthy children aged 1 - 18 yrs. and provides information about androgen function in this age period. These hormones are important markers of androgen profile in many endocrine diseases in both sexes and the established reference range will serve for a prompt diagnosis and a regular therapeutic control in CAN, PCOS, hyperandrogenism etc

  8. IGF binding proteins.

    Science.gov (United States)

    Bach, Leon A

    2017-12-18

    Insulin-like growth factor binding proteins (IGFBPs) 1-6 bind IGFs but not insulin with high affinity. They were initially identified as serum carriers and passive inhibitors of IGF actions. However, subsequent studies showed that, although IGFBPs inhibit IGF actions in many circumstances, they may also potentiate these actions. IGFBPs are widely expressed in most tissues, and they are flexible endocrine and autocrine/paracrine regulators of IGF activity, which is essential for this important physiological system. More recently, individual IGFBPs have been shown to have IGF-independent actions. Mechanisms underlying these actions include (i) interaction with non-IGF proteins in compartments including the extracellular space and matrix, the cell surface and intracellularly; (ii) interaction with and modulation of other growth factor pathways including EGF, TGF- and VEGF; and (iii) direct or indirect transcriptional effects following nuclear entry of IGFBPs. Through these IGF-dependent and IGF-independent actions, IGFBPs modulate essential cellular processes including proliferation, survival, migration, senescence, autophagy and angiogenesis. They have been implicated in a range of disorders including malignant, metabolic, neurological and immune diseases. A more complete understanding of their cellular roles may lead to the development of novel IGFBP-based therapeutic opportunities.

  9. Enrichment and Identification of the Most Abundant Zinc Binding Proteins in Developing Barley Grains by Zinc-IMAC Capture and Nano LC-MS/MS

    Directory of Open Access Journals (Sweden)

    Giuseppe Dionisio

    2018-01-01

    Full Text Available Background: Zinc accumulates in the embryo, aleurone, and subaleurone layers at different amounts in cereal grains. Our hypothesis is that zinc could be stored bound, not only to low MW metabolites/proteins, but also to high MW proteins as well. Methods: In order to identify the most abundant zinc binding proteins in different grain tissues, we microdissected barley grains into (1 seed coats; (2 aleurone/subaleurone; (3 embryo; and (4 endosperm. Initial screening for putative zinc binding proteins from the different tissue types was performed by fractionating proteins according to solubility (Osborne fractionation, and resolving those via Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE followed by polyvinylidene fluoride (PVDF membrane blotting and dithizone staining. Selected protein fractions were subjected to Zn2+-immobilized metal ion affinity chromatography, and the captured proteins were identified using nanoscale liquid chromatography coupled to tandem mass spectrometry (nanoLC-MS/MS. Results: In the endosperm, the most abundant zinc binding proteins were the storage protein B-hordeins, gamma-, and D-hordeins, while in the embryo, 7S globulins storage proteins exhibited zinc binding. In the aleurone/subaleurone, zinc affinity captured proteins were late abundant embryogenesis proteins, dehydrins, many isoforms of non-specific lipid transfer proteins, and alpha amylase trypsin inhibitor. Conclusions: We have shown evidence that abundant barley grain proteins have been captured by Zn-IMAC, and their zinc binding properties in relationship to the possibility of zinc storage is discussed.

  10. 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.

  11. Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period

    DEFF Research Database (Denmark)

    Andersson, Anna-Maria; Carlsen, Elisabeth; Petersen, Jørgen Holm

    2003-01-01

    To obtain information on the scale of the intraindividual variation in testicular hormone, blood samples for inhibin B determination were collected monthly in 27 healthy male volunteers during a 17-month period. In addition, the traditional reproductive hormones FSH, LH, testosterone, estradiol....... A seasonal variation was observed in LH and testosterone levels, but not in the levels of the other hormones. The seasonal variation in testosterone levels could be explained by the variation in LH levels. The seasonal variation in LH levels seemed to be related to the mean air temperature during the month...... levels in men. The peak levels of both LH and testosterone were observed during June-July, with minimum levels present during winter-early spring. Air temperature, rather than light exposure, seems to be a possible climatic variable explaining the seasonal variation in LH levels....

  12. Genetic Basis of Variation in Rice Seed Storage Protein (Albumin, Globulin, Prolamin, and Glutelin) Content Revealed by Genome-Wide Association Analysis.

    Science.gov (United States)

    Chen, Pingli; Shen, Zhikang; Ming, Luchang; Li, Yibo; Dan, Wenhan; Lou, Guangming; Peng, Bo; Wu, Bian; Li, Yanhua; Zhao, Da; Gao, Guanjun; Zhang, Qinglu; Xiao, Jinghua; Li, Xianghua; Wang, Gongwei; He, Yuqing

    2018-01-01

    Rice seed storage protein (SSP) is an important source of nutrition and energy. Understanding the genetic basis of SSP content and mining favorable alleles that control it will be helpful for breeding new improved cultivars. An association analysis for SSP content was performed to identify underlying genes using 527 diverse Oryza sativa accessions grown in two environments. We identified more than 107 associations for five different traits, including the contents of albumin (Alb), globulin (Glo), prolamin (Pro), glutelin (Glu), and total SSP (Total). A total of 28 associations were located at previously reported QTLs or intervals. A lead SNP sf0709447538, associated for Glu content in the indica subpopulation in 2015, was further validated in near isogenic lines NIL(Zhenshan97) and NIL(Delong208), and the Glu phenotype had significantly difference between two NILs. The association region could be target for map-based cloning of the candidate genes. There were 13 associations in regions close to grain-quality-related genes; five lead single nucleotide polymorphisms (SNPs) were located less than 20 kb upstream from grain-quality-related genes ( PG5a , Wx , AGPS2a , RP6 , and, RM1 ). Several starch-metabolism-related genes ( AGPS2a , OsACS6 , PUL , GBSSII , and ISA2 ) were also associated with SSP content. We identified favorable alleles of functional candidate genes, such as RP6 , RM1 , Wx , and other four candidate genes by haplotype analysis and expression pattern. Genotypes of RP6 and RM1 with higher Pro were not identified in japonica and exhibited much higher expression levels in indica group. The lead SNP sf0601764762, repeatedly detected for Alb content in 2 years in the whole association population, was located in the Wx locus that controls the synthesis of amylose. And Alb content was significantly and negatively correlated with amylose content and the level of 2.3 kb Wx pre-mRNA examined in this study. The associations or candidate genes identified would

  13. Induction Therapy With Antithymocyte Globulin in Patients Undergoing Cardiac Transplantation Is Associated With Decreased Coronary Plaque Progression as Assessed by Intravascular Ultrasound.

    Science.gov (United States)

    Azarbal, Babak; Cheng, Richard; Vanichsarn, Christopher; Patel, Jignesh K; Czer, Lawrence S; Chang, David H; Kittleson, Michelle M; Kobashigawa, Jon A

    2016-01-01

    Antithymocyte globulin (ATG) is used as induction therapy after cardiac transplant for enhancing immunosuppression and delaying the initiation of nephrotoxic drugs. It is unknown if ATG induction is associated with decreased coronary plaque progression by intravascular ultrasound (IVUS). Patients transplanted between March 2010 and December 2012 with baseline and 1-year IVUS were included. All patients transplanted were included in a secondary analysis. Change in plaque progression was measured in a blinded fashion on matched coronary segments and contrasted between patients induced with ATG and those who were not. One hundred and three patients were included in IVUS arms. Mean age at transplant was 55.8 ± 12.6 years, and 33.0% were female. Patients induced with ATG were more sensitized (54.3% versus 14.3%). Plaque progression was attenuated in patients who received ATG by changes in maximal intimal area (1.0 ± 1.2 versus 2.3 ± 2.6 mm(2); P = 0.001), maximal percent stenosis (6.3 ± 7.9 versus 12.8 ± 12.3%; = 0.003), maximal intimal thickness (0.2 ± 0.2 versus 0.3 ± 0.3 mm; P = 0.035), and plaque volume (0.5 ± 0.7 versus 1.0 ± 1.3 mm(3)/mm; P = 0.016). Rapid plaque progression by maximal percent stenosis (≥ 20%) occurred less frequently in the ATG arm (4.3% versus 26.3; P = 0.003). Survival (P = 0.242) and any treated rejection (P = 0.166) were not statistically different between groups. Patients receiving ATG had a higher rate of first-year infection (P = 0.003), perhaps related to increased intravenous antibiotic use immediately postoperatively, and a trend toward more biopsy-proven rejection (P = 0.073). Induction therapy with ATG is associated with reduced first-year coronary plaque progression as assessed by IVUS, despite an increased prevalence of sensitized patients with a trend toward more rejection. © 2016 American Heart Association, Inc.

  14. A New Enzyme-Linked Immunosorbent Assay for a Total Anti-T Lymphocyte Globulin Determination: Development, Analytical Validation, and Clinical Applications.

    Science.gov (United States)

    Montagna, Michela; La Nasa, Giorgio; Bernardo, Maria E; Piras, Eugenia; Avanzini, Maria A; Regazzi, Mario; Locatelli, Franco

    2017-06-01

    Anti-T lymphocyte globulin (ATLG) modulates the alloreactivity of T lymphocytes, reducing the risk of immunological posttransplant complications, in particular rejection and graft-versus-host disease, after allogeneic hematopoietic stem cell transplantation (HSCT). We developed and validated a new enzyme-linked immunosorbent assay (ELISA) method to measure serum levels of total ATLG and evaluate the pharmacokinetics (PK) of the drug in children with β-Thalassemia, receiving allogeneic HSCT. Diluted serum samples were incubated with Goat-anti-Rabbit IgG antibody coated on a microtiter plate and then, with Goat-anti-Human IgG labeled with horseradish peroxidase. After incubation and washings, substrate solution was added and absorbance was read at 492 nm. ATLG concentrations in samples were determined by interpolation from a standard curve (range: 200-0.095 ng/mL), prepared by diluting a known amount of ATLG in phosphate-buffered saline (PBS). Low, medium, and high-quality control concentrations were 1.56, 6.25, and 25 ng/mL, respectively. This method was developed and validated within the acceptance criteria in compliance with the Guidelines for a biological method validation: the sensitivity of the method was 0.095 ng/mL. We analyzed serum samples from 14 children with β-Thalassemia who received ATLG (Grafalon) at a dose of 10 mg/kg administered as intravenous (IV) infusion on days -5, -4, and -3 before HSCT (day 0). Blood sampling for PK evaluation was performed on days -5, -4, and -3 before and after drug infusion; and then from day -2 to +56. The median total ATLG levels pre-IVand post-IV were 0 and 118 mcg/mL on day -5; 85.9 and 199.2 mcg/mL on day -4; 153 and 270.9 mcg/mL on day -3, respectively. The median PK values of CL was 0.0029 (range: 0.0028-0.0057) L·kg·d, Vd was 0.088 (range: 0.025-0.448) L/kg and t1/2 was 20.2 (range: 5.8-50.2) days. These data suggest that given the marked interindividual variability of total ATLG disposition, the development of

  15. Genetic Basis of Variation in Rice Seed Storage Protein (Albumin, Globulin, Prolamin, and Glutelin Content Revealed by Genome-Wide Association Analysis

    Directory of Open Access Journals (Sweden)

    Pingli Chen

    2018-05-01

    Full Text Available Rice seed storage protein (SSP is an important source of nutrition and energy. Understanding the genetic basis of SSP content and mining favorable alleles that control it will be helpful for breeding new improved cultivars. An association analysis for SSP content was performed to identify underlying genes using 527 diverse Oryza sativa accessions grown in two environments. We identified more than 107 associations for five different traits, including the contents of albumin (Alb, globulin (Glo, prolamin (Pro, glutelin (Glu, and total SSP (Total. A total of 28 associations were located at previously reported QTLs or intervals. A lead SNP sf0709447538, associated for Glu content in the indica subpopulation in 2015, was further validated in near isogenic lines NIL(Zhenshan97 and NIL(Delong208, and the Glu phenotype had significantly difference between two NILs. The association region could be target for map-based cloning of the candidate genes. There were 13 associations in regions close to grain-quality-related genes; five lead single nucleotide polymorphisms (SNPs were located less than 20 kb upstream from grain-quality-related genes (PG5a, Wx, AGPS2a, RP6, and, RM1. Several starch-metabolism-related genes (AGPS2a, OsACS6, PUL, GBSSII, and ISA2 were also associated with SSP content. We identified favorable alleles of functional candidate genes, such as RP6, RM1, Wx, and other four candidate genes by haplotype analysis and expression pattern. Genotypes of RP6 and RM1 with higher Pro were not identified in japonica and exhibited much higher expression levels in indica group. The lead SNP sf0601764762, repeatedly detected for Alb content in 2 years in the whole association population, was located in the Wx locus that controls the synthesis of amylose. And Alb content was significantly and negatively correlated with amylose content and the level of 2.3 kb Wx pre-mRNA examined in this study. The associations or candidate genes identified would provide

  16. Drug-binding ability of human serum albumin at children with chronic virus hepatitis radiochemical definition method

    International Nuclear Information System (INIS)

    Kim, A.A.; Dadakhanov, J.A.; Djuraeva, G.T.; Shukurov, B.V.; Mavlyanov, I.R.

    2006-01-01

    chronic virus hepatitis B and C at children the hypoproteinaemia and disproteinemia are observed. Thus the contents of common protein and albumin fraction at chronic hepatitis B is reduced in comparison with control group 1,3 times on the average (P<0,05). It was marked disproteinemia due to increasing of gamma-globulin fraction of blood serum. At a chronic virus hepatitis B at children the ability of serum albumin to bind the tritium labeled drotaverine hydrochloride was reduced in comparison with control groip on the average in 1,3 times. At a chronic hepatitis C hypoproteinemia was expressed less than at a chronic virus hepatitis B, however paid to itself attention more expressed disproteinemia due to increasing of gamma-globulin fraction. Thus ability of serum albumin to bind the tritium labeled drotaverine hydrochloride dropped in comparison with control group on the average in 1,5 times (P<0,05). Thus, received results testify that at a chronic virus hepatitis B and C at children infringement of complexing properties of albumin of a blood is marked that testifies to downstroke of drug-binding function. The radiochemical method of definition of ability of serum albumin to bind the tritium labeled drotaverine hydrochloride is efficient and high informative. (author)

  17. Obesity, serum steroid levels, and pulsatile gonadotropin secretion in polycystic ovarian disease.

    Science.gov (United States)

    Laatikainen, T; Tulenheimo, A; Andersson, B; Kärkkäinen, J

    1983-04-01

    Serum binding capacity of sex-hormone binding globulin (SHBG-BC), steroid concentrations, and secretion patterns of LH and FSH were compared between groups of seven nonobese and seven obese patients with polycystic ovarian disease (PCOD). Obese patients with PCOD differed from those with normal weight in having very low SHBG-BC and elevated serum levels of free and albumin bound testosterone. Compared to healthy women in the follicular phase, both nonobese and obese patients with PCOD showed equally elevated serum levels of androstenedione, estrone, and albumin-bound and free estradiol. Pattern of gonadotropin secretion was studied from blood samples taken at 15 min intervals for 6 h. In 6 patients of both groups low pulses of FSH were found coincidently with pulses of LH. Serum level of LH showed a clear pulsatile pattern in all patients with PCOD, varying from 4.5 to 7.5 pulses per 6 h. The mean pulse rate in the groups of nonobese and obese patients with PCOD was similar, 5.9 pulses per 6 h. In the obese patients the mean LH levels were, however, less elevated and the pulse amplitudes were smaller than those in the nonobese patients. We suggest that this difference is due to high levels of biologically active testosterone in obese patients with PCOD.

  18. Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Pedersen, A T

    1997-01-01

    Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH......-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing...... hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle...

  19. Pictorial binding: endeavor to classify

    Directory of Open Access Journals (Sweden)

    Zinchenko S.

    2015-01-01

    Full Text Available The article is devoted to the classification of bindings of the 1-19th centuries with a unique and untypical book binding decoration technique (encaustic, tempera and oil paintings. Analysis of design features, materials and techniques of art decoration made it possible to identify them as a separate type - pictorial bindings and divide them into four groups. The first group consists of Coptic bindings, decorated with icon-painting images in encaustic technique. The second group is made up of leather Western bindings of the 13-14th centuries, which have the decoration and technique of ornamentation close to iconography. The third group involves parchment bindings, ornamentation technique of which is closer to the miniature. The last group comprises bindings of East Slavic origin of the 15-19th centuries, decorated with icon-painting pictures made in the technique of tempera or oil painting. The proposed classification requires further basic research as several specific kinds of bindings have not yet been investigated

  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 express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin-mediated uptake, reveal (125)I-labeled FBP uptake which is inhibited...

  1. Bioavailability of Oral Hydrocortisone Corrected for Binding Proteins and Measured by LC-MS/MS Using Serum Cortisol and Salivary Cortisone.

    Science.gov (United States)

    Johnson, T N; Whitaker, M J; Keevil, B; Ross, R J

    2018-01-01

    The assessment absolute bioavailability of oral hydrocortisone is complicated by its saturable binding to cortisol binding globulin (CBG). Previous assessment of bioavailability used a cortisol radioimmunoassay which has cross reactivity with other steroids. Salivary cortisone is a measure of free cortisol and LC-MS/MS is the gold standard method for measuring steroids. We here report the absolute bioavailability of hydrocortisone calculated using serum cortisol and salivary cortisone measured by LC-MS/MS. 14 healthy male dexamethasone suppressed volunteers were administered 20 mg hydrocortisone either intravenously or orally by tablet. Samples of serum and saliva were taken and measured for cortisol and cortisone by LC-MS/MS. Serum cortisol was corrected for saturable binding using published data and pharmacokinetic parameters derived using the program WinNonlin. The mean (95% CI) bioavailability of oral hydrocortisone calculated from serum cortisol, unbound serum cortisol and salivary cortisone was 1.00 (0.89-1.14); 0.88 (0.75-1.05); and 0.93 (0.83-1.05), respectively. The data confirm that, after oral administration, hydrocortisone is completely absorbed. The data derived from serum cortisol corrected for protein binding, and that from salivary cortisone, are similar supporting the concept that salivary cortisone reflects serum free cortisol levels and that salivary cortisone can be used as a non-invasive method for measuring the pharmacokinetics of hydrocortisone.

  2. 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...

  3. Short Communication: Testosterone Measured with an Automatic Immunoassay Compares Reasonbly Well to Results Obtained by LC-MS/MS

    DEFF Research Database (Denmark)

    Knudsen, Cindy Søndersø; Højskov, Carsten Schriver; Møller, Holger Jon

    2016-01-01

    Background: Previous studies have reported problems measuring testosterone with immunological assays. Here we explore an automatic second generation immunoassay compared to a LC-MS/MS method. Methods: We collected blood samples from 76 women and measured testosterone, progesterone, gender...... hormonebinding globulin (SHBG), and albumin employing Cobas e601/c501. Testosterone, androstenedione (andro), dehydroepiandrosterone sulphate (DHEAS), and 17-hydroxyprogesterone (17-OHP) concentrations were measured employing LC-MS/MS. We evaluated the difference between testosterone measured by the two methods...... and examined the potential interference from the selected steroids and bindings proteins. Results: Testosterone concentrations measured by the two methods yielded: Cobas e601 = 1.240 x (LC-MS/MS) - 0.197, r = 0.84, for testosterone concentrations between 0.22 - 4.9 nmol/L. A positive correlation was observed...

  4. Elevated serum IGF-I, but unaltered sex steroid levels, in healthy boys with pubertal gynaecomastia

    DEFF Research Database (Denmark)

    Mieritz, Mikkel G; Sorensen, Kaspar; Aksglaede, Lise

    2014-01-01

    OBJECTIVE: Pubertal gynaecomastia is a very common condition. Although the underlying aetiology is poorly understood, it is generally accepted that excess of oestrogens and deficit of androgens are involved in the pathogenesis. Furthermore, adiposity as well as the GH/IGF-I axis may play a role....... In this study, we elucidate the association of adiposity and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), testosterone, oestrogen, IGF-I and IGFBP-3 with the presence of pubertal gynaecomastia in a large cohort of healthy boys. PATIENTS: A total...... of 501 healthy Danish school boys (aged 6·1-19·8 year) from the COPENHAGEN Puberty Study. MEASUREMENTS: Anthropometry and pubertal stages (PH1-6 and G1-5) were evaluated, and the presence of gynaecomastia was assessed. Body fat percentage was calculated by means of four skin folds and impedance...

  5. Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio

    DEFF Research Database (Denmark)

    Holm, Mette; Rajpert-De Meyts, Ewa; Andersson, Anna-Maria

    2003-01-01

    were examined using a semi-quantitative stereological method. In patients, serum concentrations of testosterone, sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol and inhibin-B were correlated with the findings on histological examination......, with the exception of testes with bilateral micronodules, which had significantly increased Leydig cell volume compared to those without micronodules. The number of micronodules correlated positively to LH (r = 0.577, p ... in the hyperstimulated testes, as reflected by an increased LH/testosterone ratio. In conclusion, Leydig cell micronodules were more frequent in biopsies with impaired spermatogenesis and associated with decreased ratios of testicular hormones to gonadotrophins. The presence of micronodules thus seems...

  6. 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...... logistic regression models investigated associations between markers and PCa. Mixed models were used to describe kinetics. Sensitivity and specificity of using tPSA >4 ng/ml to predict PCa was calculated. Receiver operating characteristic curves were used to identify optimal cutoffs in HIV+ men for total...

  7. Does last week's alcohol intake affect semen quality or reproductive hormones?

    DEFF Research Database (Denmark)

    Hansen, M L; Thulstrup, A M; Bonde, J P

    2012-01-01

    The association between last 5 days of alcohol intake, semen quality and reproductive hormones was estimated in this cross-sectional study among 347 men. Conventional semen characteristics, DNA fragmentation index and reproductive hormones (testosterone, estradiol, sex hormone-binding globulin...... (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and inhibin B) were determined. There was a tendency towards lower semen characteristics at higher intake of alcohol past 5 days, albeit with no statistically significant dose-response association. The ratio between free estradiol...... and free testosterone was higher at higher alcohol intake during the 5 days preceding semen sampling. In conclusion, alcohol intake was associated with impairment of most semen characteristics but without a coherent dose-response pattern. The study indicates an association between recent alcohol intake...

  8. Changes in serum concentrations of total and free testosterone in young and middle-aged men

    International Nuclear Information System (INIS)

    Wang Guohong; Xu Ruiji; Zhang Zhongshu

    2011-01-01

    To determine changes in serum concentrations of total and free testosterone in young and middle-aged men.the healthy men (n=126) were divided 20-29 yr, 30-39 yr and 40-49 yr three groups,their serum levels of total testosterone (T), free testosterone (FT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG) and estradiol (E2) were detected. The results were statically analyzed. The results showed that the levels of serum T and FT was found significantly decreased in 30-39 yr group than in 20-29 yr group (15.06±13 nmol/L vs 20.41±86 nmol/L, P<0.01; 9.36±95 pg/L vs 11.48±88 pg/L, P<0.05; respectively). There were young trends that age-related decline in androgen levels. (authors)

  9. Effect of dietary supplementation of binahong leaf meal, betel nut meal or their combination on serum albumin and globulin, fecal endoparasites and bacterial counts in milk of Saanen goats suffering from subclinical mastitis

    Directory of Open Access Journals (Sweden)

    Endang Kusumanti

    2017-10-01

    Full Text Available The effect was investigated of dietary supplementation of binahong (Anredera cordifolia (Ten. Steenis leaf meal, betel nut (Arecha catechu L. meal or their combination on serum albumin and globulin, fecal endoparasites and bacterial counts in the milk of Saanen goats suffering from subclinical mastitis. The goats were randomly allotted to one of four experimental groups: control diet (diet without binahong leaf meal or betel nut meal; CON, diet supplemented with binahong leaf meal (1 g/kg body weight; BNH, diet supplemented with betel nut meal (1 g/kg body weight; BTN and diet supplemented with a combination of binahong leaf meal and betel nut meal (both 0.5 g/kg body weight; BNH + BTN. After 14 d treatment, the pH was higher (p  0.05 in levels of serum albumin and globulin and milk production across the treatment diets. In conclusion, dietary supplementation of binahong leaf meal, betel nut meal and a combination of both showed potential to reduce the load of endoparasites in the gastrointestinal tract and to reduce subclinical mastitis in lactating Saanen goats. Keywords: Antibiotics, Betel nut, Binahong, Saanen goat, Subclinical mastitis

  10. [3]tetrahydrotrazodone binding. Association with serotonin binding sites

    International Nuclear Information System (INIS)

    Kendall, D.A.; Taylor, D.P.; Enna, S.J.

    1983-01-01

    High (17 nM) and low (603 nM) affinity binding sites for [ 3 ]tetrahydrotrazodone ([ 3 ] THT), a biologically active analogue of trazodone, have been identified in rat brain membranes. The substrate specificity, concentration, and subcellular and regional distributions of these sites suggest that they may represent a component of the serotonin transmitter system. Pharmacological analysis of [ 3 ]THT binding, coupled with brain lesion and drug treatment experiments, revealed that, unlike other antidepressants, [ 3 ] THT does not attach to either a biogenic amine transporter or serotonin binding sites. Rather, it would appear that [ 3 ]THT may be an antagonist ligand for the serotonin binding site. This probe may prove of value in defining the mechanism of action of trazodone and in further characterizing serotonin receptors

  11. Protein binding of psychotropic agents

    International Nuclear Information System (INIS)

    Hassan, H.A.

    1990-01-01

    Based upon fluorescence measurements, protein binding of some psychotropic agents (chlorpromazine, promethazine, and trifluoperazine) to human IgG and HSA was studied in aqueous cacodylate buffer, PH7. The interaction parameters determined from emission quenching of the proteins. The interaction parameters determined include the equilibrium constant (K), calculated from equations derived by Borazan and coworkers, the number of binding sites (n) available to the monomer molecules on a single protein molecule. The results revealed a high level of affinity, as reflected by high values of K, and the existence of specific binding sites, since a limited number of n values are obtained. 39 tabs.; 37 figs.; 83 refs

  12. Binding protein for vitamin D and its metabolites in rat mesenteric lymph

    International Nuclear Information System (INIS)

    Dueland, S.; Bouillon, R.; Van Baelen, H.; Pedersen, J.I.; Helgerud, P.; Drevon, C.A.

    1985-01-01

    A protein with high affinity for vitamin D3 and 25-hydroxyvitamin D3 in rat mesenteric lymph has been studied. Mesenteric lymph was collected after duodenal instillation of radiolabeled vitamin D3 and 25-hydroxyvitamin D3. As previously described, approximately 10% of vitamin D3 and 95% of 25-hydroxyvitamin D3 recovered in mesenteric lymph were associated with the alpha-globulin fractions. The radioactive vitamin D3 recovered in the lymph fraction with d greater than 1.006 (free of chylomicrons) coeluted with purified rat serum binding protein for vitamin D and its metabolites (DBP) from an antirat DBP column. The results obtained by immunoblotting after sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that this protein in mesenteric lymph had molecular weight and immunological properties identical with purified serum DBP. Purified serum DBP labeled with 125 I was injected intravenously and mesenteric lymph was collected. results suggesting that DBP may be transferred from blood to mesenteric lymph and that plasma and lymph DBP may have a similar origin

  13. The comparison of the measurement of human serum thyroid globulin auto-antibodies and thyroid peroxidase auto-antibodies by CLIA and RIA

    International Nuclear Information System (INIS)

    Song Ailing; Guo Zhisheng; Sun Meili; Lian Xiaolan; Bai Yao

    2003-01-01

    The serum levels of thyroid globulin auto-antibodies (Anti-TgAb) and thyroid peroxidase auto-antibodies (Anti-TpoAb) in 37 patients with hyperthyroidism, 30 with chronic lymphocytic thyroidism, 36 with other endocrine diseases and 35 healthy persons were determined by chemiluminescence immunoassay (CLIA) and RIA, and the results were compared with each other. The results showed: (1) The within-batch CVs of CLIA and RIA were 3.0% and 10.0%, and the between-batch CVs were 3.9% and 15.0%, respectively; (2) The levels of serum anti-TgAb and Anti-TpoAb in healthy people were 25.9±9.6 U/mL and 31.4±6.7U/mL by CLIA, while those were 11.2±2.8% and 8.7±3.0% by RIA; (3) The levels of serum anti-TgAb and Anti-TpoAb of chronic lymphocytic thyroidism were 292.6±334.1U/mL and 5043.3±3196.1U/mL (n=17) by CLIA, while those were 56.4±11.2% (n=21) and 35.4±6.9% (n=21) by RIA. It showed that levels of anti-TgAb and Anti-TpoAb of chronic lymphocytic thyroidism were much higher than that in healthy people by CLIA (P<0.001). Furthermore, the levels of Anti-TpoAb were more than 100 times of that in health people by CLIA and the specificity of Anti-TpoAb was higher; (4) The levels of anti-TgAb and Anti-TpoAb in hyperthyroid patients were 202.3±506.3U/mL and 452.9±645.8U/mL by CLIA, while those were 28.8±20.0% and 22.6±14.2% by RIA. The levels of Anti-TgAb and Anti-TpoAb in patients with other endocrine disease were 28.7±15.0U/mL and 58.8±45.7U/mL by CLIA, while those were 10.2±13.3% and 7.9±7.7% by RIA; (5) These is a significant correlation between the two methods: Anti TgAb r=0.695; and Anti-TpoAb r=0.489. This results show that it may be more sensitive and specific test of Anti-TpoAb with CLIA than with RIA. CLIA should be used as a powerful diagnostic tool in clinical because it is simple, quick and without radioisotope

  14. Superresolution microscopy with transient binding.

    Science.gov (United States)

    Molle, Julia; Raab, Mario; Holzmeister, Susanne; Schmitt-Monreal, Daniel; Grohmann, Dina; He, Zhike; Tinnefeld, Philip

    2016-06-01

    For single-molecule localization based superresolution, the concentration of fluorescent labels has to be thinned out. This is commonly achieved by photophysically or photochemically deactivating subsets of molecules. Alternatively, apparent switching of molecules can be achieved by transient binding of fluorescent labels. Here, a diffusing dye yields bright fluorescent spots when binding to the structure of interest. As the binding interaction is weak, the labeling is reversible and the dye ligand construct diffuses back into solution. This approach of achieving superresolution by transient binding (STB) is reviewed in this manuscript. Different realizations of STB are discussed and compared to other localization-based superresolution modalities. We propose the development of labeling strategies that will make STB a highly versatile tool for superresolution microscopy at highest resolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Elevated Serum Bisphenol A Level in Patients with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Qinmei Xiong

    2015-05-01

    Full Text Available background: This study aimed to determine serum Bisphenol A (BPA concentrations in patients with dilated cardiomyopathy (DCM as well as the association between serum BPA and several hormonal parameters in DCM patients compared with a healthy control group. Materials and methods: Eighty-eight DCM patients and 88 age- and gender-matched healthy controls were included. Serum BPA levels and several hormonal parameters (including total testosterone (T, sex hormone-binding globulin (SHBG and estradiol (E2 were measured by using corresponding ELISA Kits. The free androgen index (FAI was calculated by the formula: total T in nmol/L × 100/SHBG in nmol/L. Results: BPA levels in the total DCM group were significantly higher compared with that in the controls (6.9 ± 2.7 ng/mL vs. 3.8 ± 1.9 ng/mL, p < 0.001. Significant difference was also observed in SHBG and FAI between DCM patients and controls, (76.9 ± 30.9 nM/L vs. 41.0 ± 15.6 nM/L and 2.9 ± 3.5 vs.5.3 ± 2.6, respectively, both of p < 0.001. Similar trends were observed in the male and female subgroup. Mean T level was lower in DCM group than in control group (540.8 ± 186.0 pg/mL vs. 656.3 ± 112.9 pg/mL, p < 0.001. Linear regression analysis has shown that increasing serum BPA levels were statistically significantly associated with increased SHBG levels. However, no statistical difference was noted for E2. Conclusion: Our findings firstly demonstrated that BPA exposure increased in DCM patients compared with that in healthy controls, while FAI and T levels decreased. SHBG presented a positive association with BPA. It is concluded that hormone disorder induced by BPA exposure might be an environmental factor in the pathology of DCM.

  16. To bind or not to bind? Different temporal binding effects from voluntary pressing and releasing actions.

    Science.gov (United States)

    Zhao, Ke; Chen, Yu-Hsin; Yan, Wen-Jing; Fu, Xiaolan

    2013-01-01

    Binding effect refers to the perceptual attraction between an action and an outcome leading to a subjective compression of time. Most studies investigating binding effects exclusively employ the "pressing" action without exploring other types of actions. The present study addresses this issue by introducing another action, releasing action or the voluntary lifting of the finger/wrist, to investigate the differences between voluntary pressing and releasing actions. Results reveal that releasing actions led to robust yet short-lived temporal binding effects, whereas pressing condition had steady temporal binding effects up to super-seconds. The two actions also differ in sensitivity to changes in temporal contiguity and contingency, which could be attributed to the difference in awareness of action. Extending upon current models of "willed action," our results provide insights from a temporal point of view and support the concept of a dual system consisting of predictive motor control and top-down mechanisms.

  17. 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.

  18. The Association between Androgenic Hormone Levels and the Risk of Developing Coronary Artery Disease (CAD).

    Science.gov (United States)

    Allameh, Farzad; Pourmand, Gholamreza; Bozorgi, Ali; Nekuie, Sepideh; Namdari, Farshad

    2016-01-01

    The aim of the study was to evaluate the relationship between the serum levels of androgens and Coronary Artery Disease (CAD) in an Iranian population. Male individuals admitted to Tehran Heart Center and Sina Hospital, Tehran, Iran from 2011-2012 were categorized into CAD and control groups based on selective coronary angiography. Baseline demographic data, including age, BMI, diabetes, and a history of hypertension were recorded. Patients were also assessed for their serum levels of total testosterone, free testosterone, estradiol, dehydroepi and rosterone sulfate (DHEA-S), and Sex Hormone Binding Globulin (SHBG). Data analysis was carried out chi-square and ANOVA tests as well as logistic regression analysis. Two hundred patients were in the CAD group and 135 individuals in control group. In the CAD group, 69 had single-vessel disease, 49 had two-vessel diseases, and 82 had three-vessel diseases. Statistically significant differences were observed between the individuals in the two groups with respect to age (PCAD group; however, the serum level of SHBG was higher in the CAD group than in the control group (P=0.007). Results of the logistic regression analysis indicated that only age (P=0.042) and diabetes (P=0.003) had significant relationships with CAD. Although the serum levels of some of the androgens were significantly different between the two groups, no association was found between androgenic hormone levels and the risk of CAD, due mainly to the effect of age and diabetes.

  19. The association of reproductive and lifestyle factors with a score of multiple endogenous hormones.

    Science.gov (United States)

    Shafrir, Amy L; Zhang, Xuehong; Poole, Elizabeth M; Hankinson, Susan E; Tworoger, Shelley S

    2014-10-01

    We recently reported that high levels of multiple sex and growth hormones were associated with increased postmenopausal breast cancer risk. Limited research has explored the relationship between reproductive, anthropometric, and lifestyle factors and levels of multiple hormones simultaneously. This cross-sectional analysis included 738 postmenopausal Nurses' Health Study participants who were controls in a breast cancer nested case-control study and had measured levels of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone sulfate, prolactin, and sex hormone binding globulin (SHBG). A score was created by summing the number of hormones a woman had above (below for SHBG) each hormone's age-adjusted geometric mean. The association between lifestyle, anthropometric, and reproductive exposures and the score was assessed using generalized linear models. The hormone score ranged from 0 to 8 with a mean of 4.0 (standard deviation = 2.2). Body mass index (BMI) and alcohol consumption at blood draw were positively associated with the hormone score: a 5 unit increase in BMI was associated with a 0.79 (95%CI: 0.63, 0.95) unit increase in the score (p hormones, whereas anthropometric and lifestyle factors, particularly BMI and alcohol consumption, tended to be associated with higher levels of multiple hormones.

  20. Plasma beta-endorphin levels in obese and non-obese patients with polycystic ovary disease.

    Science.gov (United States)

    Martínez-Guisasola, J; Guerrero, M; Alonso, F; Díaz, F; Cordero, J; Ferrer, J

    2001-02-01

    The aim of this study was to determine the influence of body weight on circulating plasma levels of beta-endorphin and insulin in women with polycystic ovary disease (PCOD), as well as the correlation between the plasma levels of beta-endorphin and insulin. One-hundred and sixty-seven consecutive subjects with PCOD were recruited, 117 of whom had normal weight (body mass index (BMI) 25). A venous blood sample was taken and plasma concentrations of beta-endorphin, insulin, gonadotropins, prolactin, progesterone, 17 beta-estradiol, estrone, androgens, dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) were measured. Mean beta-endorphin and insulin plasma levels were significantly higher (p PCOD women than in non-obese ones. Correlation analysis showed a positive association between insulin and beta-endorphin, beta-endorphin and BMI (and weight), insulin and BMI (and weight), and a negative correlation was found between insulin and SHBG. A weak association was found between beta-endorphin and luteinizing hormone (LH) in peripheral plasma. Stratified and linear regression analysis showed that plasma beta-endorphin concentrations correlate more with BMI than with insulinemia.

  1. Circulating adiponectin increases in obese women after sleeve gastrectomy or gastric bypass driving beneficial metabolic changes but with no relationship with carotid intima-media thickness.

    Science.gov (United States)

    Gómez-Martin, Jesús M; Balsa, José A; Aracil, Enrique; Insenser, María; Priego, Pablo; Escobar-Morreale, Héctor F; Botella-Carretero, José I

    2017-10-12

    Obesity surgery induces beneficial effects in metabolic and cardiovascular parameters. Adiponectin increase might be associated with some of these changes. However, direct comparison between different surgical techniques has not been extensively performed. We studied 20 obese women submitted to laparoscopic Roux en Y gastric bypass (RYGB) and 20 to sleeve gastrectomy (SG). Twenty control women matched for age and baseline metabolic profiles were also included. Both patients and controls were followed up for one year after surgery or conventional treatment with diet and exercise, respectively. Serum adiponectin was measured at baseline, 6 months and 1 year after, as well as lipid profiles, sex hormone binding globulin (SHBG), fasting glucose and insulin. Carotid intima-media thickness was measured by ultrasonography at baseline and after 1 year. Circulating adiponectin increased after obesity surgery (more markedly following RYGB than after SG), whereas no changes were observed in the controls (Wilks' λ = 0.659, P media thickness (r = -0.055, P = 0.679). RYGB induces a higher increase in adiponectin than SG, which parallels SHBG, the reduction of fasting insulin and insulin resistance. On the other hand, no association was found with carotid intima-media, lipid profiles or blood pressure. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  2. Hormonal (Cortical-Gonadotropic Axis) and Physical Changes With Two Years Intense Exercise Training in Elite Young Soccer Players.

    Science.gov (United States)

    Hammami, Mohamed Ali; Ben Abderrahman, Abderraouf; Hackney, Anthony C; Kebsi, Wiem; Owen, Adam L; Nebigh, Amar; Racil, Ghazi; Tabka, Zouhair; Zouhal, Hassane

    2017-09-01

    Hammami, MA, Ben Abderrahman, A, Hackney, AC, Kebsi, W, Owen, AL, Nebigh, A, Racil, G, Tabka, Z, and Zouhal, H. Hormonal (cortical-gonadotropic axis) and physical changes with two years intense exercise training in elite young soccer players. J Strength Cond Res 31(9): 2388-2397, 2017-The aim of this study was to investigate the effects of 2 soccer-training seasons on physical fitness and hormone concentrations in elite youth soccer players. Twenty male elite soccer players (SP, age 14.5 ± 0.4 years) and 20 male control subjects (CS, age 14.3 ± 0.3 years) participated in the study. Anthropometric measurements, aerobic (Yo-Yo Intermittent Recovery Test Level 1 [YYIRT1]) and anaerobic soccer relevant performances (jump and sprint tests), blood testosterone (T), cortisol (C), sex hormone binding globulin (SHBG), and T/C ratio were assessed 5 times (from T0 to T4) during 2 competitive seasons. Significant differences from basal values (Δ) of T, SHBG, and C between SP and CS were observed (p soccer players group compared with controls. Our findings also show that the T concentrations and power performance outcomes co-vary positively over the 2 soccer seasons in soccer players.

  3. Endocrine Changes In Egyptian Female Olympic Runners

    International Nuclear Information System (INIS)

    Bayad, M.A.; Fahmy, N.M.

    2002-01-01

    Circulating levels of testosterone (T), free testosterone (FT), and rostenedione (A) estradial 17-B (E 2 ), dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding globulin (SHBG), luteninzing hormone (LH) and cortisol (C) were estimated by RIA proccdures in the serum of two groups of athletic female runners. An eumenorrheic group (n=10), and an oligomenorrheic group (n=10), and in a healthy regularly menstruating group as control(n=20). The athletes were subjected to a stadardized Ergometer testing aiming at achieving maximal O 2 consumption. Blood samples were with drawn at rest and immediately after exercise in the eumenorrheic and oligomenorrheic groups. Samples from eumenorrheic athletes and control group were at midfollicular phase of the cycle; and randomly in the oligomenorrheicat athlets. Results revealed a state of hypercortisolism in resting eumenorrheic athletes in comparison with control, whereas the oligomenorrheic athletes showed a state of hypercortisolism, hyperandrogenism and hyperestrogenism. The estimated perameters showed remrakable significant increase after the bicycle Ergometer testing, with the exception of SHBG and DHEA-S in the athletic groups

  4. Testosterone during pregnancy and gender role behavior of preschool children: a longitudinal, population study.

    Science.gov (United States)

    Hines, Melissa; Golombok, Susan; Rust, John; Johnston, Katie J; Golding, Jean

    2002-01-01

    Levels of testosterone (T) and sex hormone-binding globulin (SHBG) were measured in blood samples from pregnant women and related to gender role behavior in 342 male and 337 female offspring at the age of 3.5 years. Gender role behavior was assessed using the Pre-School Activities Inventory, a standardized measure on which a parent indicates the child's involvement with sex-typical toys, games, and activities. Levels of T, but not SHBG, related linearly to gender role behavior in preschool girls. Neither hormone related to gender role behavior in boys. Other factors, including the presence of older brothers or sisters in the home, parental adherence to traditional sex roles, the presence of a male partner in the home, and maternal education, did not relate to gender role behavior in this sample and did not account for the relation observed between T and behavior. Although other, unmeasured factors may explain the relation, the results suggest that normal variability in T levels prenatally may contribute to the development of individual differences in the gender role behavior of preschool girls.

  5. Exercise training improves free testosterone in lifelong sedentary aging men.

    Science.gov (United States)

    Hayes, Lawrence D; Herbert, Peter; Sculthorpe, Nicholas F; Grace, Fergal M

    2017-07-01

    As the impact of high-intensity interval training (HIIT) on systemic hormones in aging men is unstudied to date, we investigated whether total testosterone (TT), sex hormone-binding globulin (SHBG), free testosterone (free-T) and cortisol (all in serum) were altered following HIIT in a cohort of 22 lifelong sedentary (62 ± 2 years) older men. As HIIT requires preconditioning exercise in sedentary cohorts, participants were tested at three phases, each separated by six-week training; baseline (phase A), following conditioning exercise (phase B) and post-HIIT (phase C). Each measurement phase used identical methods. TT was significantly increased following HIIT (~17%; P  HIIT compared to baseline (~4.5%; P  = 0.023). Cortisol remained unchanged from A to C ( P  = 0.138). The present data indicate a combination of preconditioning, and HIIT increases TT and SHBG in sedentary older males, with the HIIT stimulus accounting for a small but statistically significant increase in free-T. Further study is required to determine the biological importance of small improvements in free-T in aging men. © 2017 The authors.

  6. Differences in low-grade chronic inflammation and insulin resistance in women with previous gestational diabetes mellitus and women with polycystic ovary syndrome.

    Science.gov (United States)

    Thomann, Robert; Rossinelli, Nadia; Keller, Ulrich; Tirri, Brigitte Frey; De Geyter, Christian; Ruiz, Juan; Kränzlin, Marius; Puder, Jardena J

    2008-04-01

    Polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) are both characterized by an increase in insulin resistance. Our goal in the present study was to measure insulin resistance (as estimated by homeostasis model assessment, sex hormone-binding globulin (SHBG) and adiponectin concentrations) and parameters of low-grade inflammation in non-diabetic, non-hyperandrogenic ovulatory women with previous GDM (pGDM) and in non-diabetic women with classic PCOS, characterized by hyperandrogenism and oligo/anovulation. We evaluated 20 women with PCOS, 18 women with pGDM and 19 controls, all matched according to body mass index (BMI). Fasting blood samples were drawn in all women 3-6 days after spontaneous or dydrogesterone-induced withdrawal bleeding. Body fat distribution was assessed using dual-energy X-ray absorptiometry in all women. After adjusting for age and percent body fat, measures of insulin resistance such as SHBG and adiponectin concentrations were decreased and central obesity was increased in women with PCOS and pGDM compared with controls (all p PCOS compared with BMI-matched controls (all p insulin resistance are increased in both women with PCOS and women with pGDM, while low-grade inflammation is increased only in PCOS. PCOS and GDM might represent specific phenotypes of one disease entity with an increased risk of cardiovascular disease, whereby women with PCOS demonstrate an augmented cardiovascular risk profile.

  7. Sex hormones in Malay and Chinese men in Malaysia: are there age and race differences?

    Directory of Open Access Journals (Sweden)

    Kok-Yong Chin

    2013-01-01

    Full Text Available OBJECTIVES: Variations in the prevalence of sex-hormone-related diseases have been observed between Asian ethnic groups living in the same country; however, available data concerning their sex hormone levels are limited. The present study aimed to determine the influence of ethnicity and age on the sex hormone levels of Malay and Chinese men in Malaysia. METHODS: A total of 547 males of Malay and Chinese ethnicity residing in the Klang Valley Malaysia underwent a detailed screening, and their blood was collected for sex hormones analyses. RESULTS: Testosterone levels were normally distributed in the men (total, free and non-sex hormone-binding globulin (SHBG bound fractions, and significant ethnic differences were observed (p<0.05; however, the effect size was small. In general, testosterone levels in males began to decline significantly after age 50. Significant ethnic differences in total, free and non-SHBG bound fraction estradiol levels were observed in the 20-29 and 50-59 age groups (p<0.05. The estradiol levels of Malay men decreased as they aged, but they increased for Chinese men starting at age 40. CONCLUSIONS: Small but significant differences in testosterone levels existed between Malay and Chinese males. Significant age and race differences existed in estradiol levels. These differences might contribute to the ethnic group differences in diseases related to sex hormones, which other studies have found in Malaysia.

  8. Sex hormones in Malay and Chinese men in Malaysia: are there age and race differences?

    Directory of Open Access Journals (Sweden)

    Kok-Yong Chin

    Full Text Available OBJECTIVES: Variations in the prevalence of sex-hormone-related diseases have been observed between Asian ethnic groups living in the same country; however, available data concerning their sex hormone levels are limited. The present study aimed to determine the influence of ethnicity and age on the sex hormone levels of Malay and Chinese men in Malaysia. METHODS: A total of 547 males of Malay and Chinese ethnicity residing in the Klang Valley Malaysia underwent a detailed screening, and their blood was collected for sex hormones analyses. RESULTS: Testosterone levels were normally distributed in the men (total, free and non-sex hormone-binding globulin (SHBG bound fractions, and significant ethnic differences were observed (p<0.05; however, the effect size was small. In general, testosterone levels in males began to decline significantly after age 50. Significant ethnic differences in total, free and non-SHBG bound fraction estradiol levels were observed in the 20-29 and 50-59 age groups (p<0.05. The estradiol levels of Malay men decreased as they aged, but they increased for Chinese men starting at age 40. CONCLUSIONS: Small but significant differences in testosterone levels existed between Malay and Chinese males. Significant age and race differences existed in estradiol levels. These differences might contribute to the ethnic group differences in diseases related to sex hormones, which other studies have found in Malaysia.

  9. Menstrual Dysfunction in Girls from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study.

    Science.gov (United States)

    Kelsey, Megan M; Braffett, Barbara H; Geffner, Mitchell E; Levitsky, Lynne L; Caprio, Sonia; McKay, Siripoom V; Shah, Rachana; Sprague, Jennifer E; Arslanian, Silva A

    2018-04-24

    Little is known about reproductive function in girls with youth-onset type 2 diabetes. To characterize girls with irregular menses, and effects of glycemic treatments on menses and sex steroids in the Treatment Options for Type 2 Diabetes in Youth (TODAY) study. Differences in demographic, metabolic, and hormonal characteristics between regular vs. irregular menses groups were tested; treatment group (metformin +/- rosiglitazone, metformin + lifestyle) effect on menses and sex steroids over time in the study was assessed. This is a secondary analysis of TODAY data. Multi-center study in an academic setting. TODAY girls not on hormonal contraception and those > 1-year post-menarche were included. Irregular menses was defined as irregular menses. Those with irregular vs. regular menses had higher body mass index (BMI) (p=0.001), AST (p=0.001), free androgen index (p=0.0003), total testosterone (p=0.01); and lower sex-hormone binding globulin (SHBG) (p=0.004) and estradiol (p=0.01). Differences remained after adjusting for BMI. There was no treatment group effect on menses or sex steroids at 12 or 24 months, and no association of sex steroids with measures of insulin sensitivity or secretion. Menstrual dysfunction is common in girls with recently diagnosed T2D and associated with alterations in sex steroids, SHBG, and AST, but not with alteration in insulin sensitivity or β-cell function, and did not improve with 2 years of anti-hyperglycemic treatment.

  10. 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.

  11. Preceding immunosuppressive therapy with antithymocyte globulin and ciclosporin increases the incidence of graft rejection in children with aplastic anaemia who underwent allogeneic bone marrow transplantation from HLA-identical siblings.

    Science.gov (United States)

    Kobayashi, Ryoji; Yabe, Hiromasa; Hara, Junichi; Morimoto, Akira; Tsuchida, Masahiro; Mugishima, Hideo; Ohara, Akira; Tsukimoto, Ichiro; Kato, Koji; Kigasawa, Hisato; Tabuchi, Ken; Nakahata, Tatsutoshi; Ohga, Shoichi; Kojima, Seiji

    2006-12-01

    The incidence of graft rejection was determined in 66 children with acquired aplastic anaemia (AA) following bone marrow transplantation (BMT) from a related donor. Eleven of 65 evaluable patients experienced either early or late rejection. Multivariate analysis identified previous immunosuppressive therapy with antithymocyte-globulin (ATG) and ciclosporin (CsA) as a risk factor for graft rejection (relative risk: 16.6, P = 0.001). Patients who received ATG and CsA had a significantly lower probability of failure-free survival than those who did not (69.7 +/- 6.2% vs. 87.9 +/- 8.0%, P = 0.044). These results suggest that BMT should be instituted immediately in children with severe AA who have human leucocyte antigen-identical siblings.

  12. Binding energies of cluster ions

    International Nuclear Information System (INIS)

    Parajuli, R.; Matt, S.; Scheier, P.; Echt, O.; Stamatovic, A.; Maerk, T.D.

    2002-01-01

    The binding energy of charged clusters may be measured by analyzing the kinetic energy released in the metastable decay of mass selected parent ions. Using finite heat bath theory to determine the binding energies of argon, neon, krypton, oxygen and nitrogen from their respective average kinetic energy released were carried out. A high-resolution double focussing two-sector mass spectrometer of reversed Nier-Johnson type geometry was used. MIKE ( mass-analysed ion kinetic energy) were measured to investigate decay reactions of mass-selected ions. For the inert gases neon (Ne n + ), argon (Ar n + ) and krypton (Kr n + ), it is found that the binding energies initially decrease with increasing size n and then level off at a value above the enthalpy of vaporization of the condensed phase. Oxygen cluster ions shown a characteristic dependence on cluster size (U-shape) indicating a change in the metastable fragmentation mechanism when going from the dimer to the decamer ion. (nevyjel)

  13. Metal binding by food components

    DEFF Research Database (Denmark)

    Tang, Ning

    for zinc binding by the investigated amino acids, peptides and proteins. The thiol group or imidazole group containing amino acids, peptides and proteins which exhibited strong zinc binding ability were further selected for interacting with zinc salts in relation to zinc absorption. The interactions...... between the above selected food components and zinc citrate or zinc phytate will lead to the enhanced solubility of zinc citrate or zinc phytate. The main driving force for this observed solubility enhancement is the complex formation between zinc and investigated food components as revealed by isothermal...... titration calorimetry and quantum mechanical calculations. This is due to the zinc binding affinity of the relatively softer ligands (investigated food components) will become much stronger than citrate or phytate when they present together in aqueous solution. This mechanism indicates these food components...

  14. 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.

  15. Intrauterine insulin resistance in fetuses of overweight mothers.

    Science.gov (United States)

    Liu, Bin; Xu, Yun; Liang, Jian-Ming; Voss, Courtney; Xiao, Huan-Yu; Sheng, Wei-Yang; Sun, Yan-Hong; Wang, Zi-Lian

    2013-01-01

    To investigate the relationship between maternal overweight and fetal insulin resistance. Nineteen overweight and 30 lean pregnant women were recruited in the present study. Maternal and fetal insulin resistance were determined by measuring sex hormone binding globulin (SHBG) concentrations in maternal venous or umbilical cord serum, respectively. Maternal age, gestational age, height, pre-gravidity weight, pre-partum weight, as well as fetal gender, birth weight, birth height, and head circumference were collected as clinical data. Fetuses of overweight mothers had larger birth weight (3.58±0.55kg vs 3.32±0.42, adjusted P=0.006) and lower SHBG concentrations (26.64±3.65 vs 34.36±7.84, adjusted P=0.007) than those of lean mothers after values were adjusted for potential cofactors. Fetal SHBG level was negatively correlated with pre-gravidity body mass index (R=-0.392, adjusted P=0.025) and weight gain during pregnancy (R=-0.332, adjusted P=0.026) even with adjustment for potential cofactors. Among the 29 pregnant women with gestational diabetes mellitus, the overweight mothers had higher H1AC levels than their lean counterparts (6.47±0.44 vs 5.74±0.52, adjusted P=0.004). Intrauterine insulin resistance is more prominent in fetuses of overweight mothers, an effect that is decreased by weight gain control during pregnancy. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  16. Evaluation of the association of vitamin D deficiency with gonadotropins and sex hormone in obese and non-obese women with polycystic ovary syndrome.

    Science.gov (United States)

    Velija-Ašimi, Zelija

    2014-02-01

    To evaluate the association of vitamin D (VD) deficiency with gonadotropins and sex hormone in obese and non-obese women with polycystic ovary syndrome (PCOS). Of the total of 140 women, thirty obese and thirty nonobese, aged 20-40 years, were included in the study. Inclusion criteria were the women with normal level of thyroid-stimulating hormone (TSH), prolactin (PRL), parathyroid hormone (PTH), and calcium, and those who had not received any medication or VD supplementation within the last 6 months. Serum 25- hydroxyvitamin D (25(OH)D), C-reactive protein (CRP), lipid profile, fasting serum glucose, basal insulin, homeostasis model analysis of insulin resistance (HOMA-IR) index, follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestrogen, total testosterone, dehidroepiandrostendion-sulphat (DHEA-S), androstendione, and sex hormone binding globulin (SHBG) were determined at follicular phase. Body mass index (BMI), weight, waist, lipids, and CRP were significantly higher in obese than in non-obese PCOS women (p=0.000). Meanwhile, insulin and HOMA-IR were also higher in the obese PCOS (p less than 0.000), and so was the fasting glucose (p=0.004). Furthermore, obese PCOS showed significantly higher level of LH (p=0.012), but lower level of progesterone (p=0.001) and androstendione (p=0.006) than in non-obese PCOS. In total 68% of PCOS women had VD deficiency but without significant difference among groups according to BMI. There was no association of VD deficiency with gonadotropins and sex hormones except SHBG. Insulin resistance was a better independent risk factor for the presence of vitamin D deficiency than SHBG. The insulin resistance and vitamin D deficiency significantly predicted the obesity risk in PCOS women.

  17. Elevated anti-Mullerian hormone in lean women may not indicate polycystic ovarian syndrome.

    Science.gov (United States)

    Bradbury, Rachel A; Lee, Paul; Smith, Howard C

    2017-10-01

    Polycystic ovarian syndrome (PCOS) is a heterogeneous disorder with clinical features shared with functional hypogonadotrophic hypogonadism (FHH). To investigate the usefulness of an elevated (>40 pmol/L) anti-Mullerian hormone (AMH) in identifying PCOS and distinguishing PCOS from FHH. 141 patients with an elevated AMH and body mass index either 30 kg/m 2 (obese) were selected and three subgroups analysed - obese, lean, lean with suspected FHH. FHH was diagnosed clinically, incorporating diet, weight and exercise history; confirmatory tests included pituitary MRIs, progestin challenges and endometrial thickness measurements. PCOS features of oligo/anovulation, polycystic ovarian morphology (PCOm) and hyperandrogenism were determined by clinical history, pelvic ultrasound, free androgen index and physical examination, respectively. Features of PCOS and blood levels of AMH, follicle-stimulating hormone, luteinising hormone, sex hormone binding globulin (SHBG) and testosterone were compared between subgroups. Of 141 patients with elevated AMH, 76 were obese and 65 lean. Greater than one-third of lean women had the clinical picture of FHH. Elevated AMH predicted PCOm and menstrual irregularity across all subgroups but uniquely associated with hyperandrogenism in the obese. Median AMH levels were similar among FHH and non-FHH women. Median SHBG levels were significantly higher (111 ± 73 vs 56 ± 31, P polycystic ovarian morphology. AMH did not assist in differentiating FHH from PCOS. A higher SHBG level shows promise as a discriminatory finding in FHH. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  18. Serum androgen levels in women who have recurrent miscarriages and their correlation with markers of endometrial function.

    Science.gov (United States)

    Okon, M A; Laird, S M; Tuckerman, E M; Li, T C

    1998-04-01

    To compare plasma androgen concentrations in women who have recurrent miscarriages and in fertile women, and to correlate the results with concentrations of the endometrial protein PP14 in uterine flushings and plasma from women who have recurrent miscarriages. Retrospective study. Hospital research unit. Women attending a recurrent miscarriage clinic and normal fertile volunteers. Ten of the women with recurrent miscarriages had polycystic ovary disease (PCOD) as assessed by ultrasonography or increased follicular LH levels. Plasma samples were obtained from the women on days LH-7, LH-4, LH+0, and LH+7 or LH+10 of a cycle. An endometrial flushing sample and a biopsy specimen were taken from women with recurrent miscarriages on day LH+7 or LH+10. Androstenedione, testosterone, and sex hormone-binding globulin (SHBG) were measured in the plasma samples. The endometrial protein PP14 was measured in the uterine flushings and in the LH+7 or LH+10 plasma samples from the women with recurrent miscarriages. Testosterone concentrations were higher in the women with recurrent miscarriages both with and without PCOD on days LH-7 and LH-4 of the cycle. Concentrations of androstenedione also were higher in the women with recurrent miscarriages, but without PCOD on day LH-7. Testosterone SHBG ratios were higher in the women with recurrent miscarriages, without PCOD compared with the controls on days LH-7, LH+0, and LH+7. Mean follicular testosterone concentrations were correlated negatively with both uterine (r = -0.47) and plasma (r = -0.49) PP14 levels on day LH+10. Mean luteal phase testosterone SHBG ratios were correlated negatively with uterine PP14 concentrations on day LH+7 of the cycle (r = -0.674). Androgen levels are higher in women who have recurrent miscarriages than in normal fertile controls. These high levels of androgens may have a detrimental effect on endometrial function.

  19. Testosterone levels and sexual function disorders in depressive female patients: effects of antidepressant treatment.

    Science.gov (United States)

    Kumsar, Şükrü; Kumsar, Neslihan Akkişi; Sağlam, Hasan Salih; Köse, Osman; Budak, Salih; Adsan, Öztuğ

    2014-02-01

    Women suffer from depression more frequently than men, which indicates that sex hormones might be involved in the etiology of this disease. The purpose of this study was to assess the relationship between testosterone and depression pathophysiology in depressive women along with sexual function. We also investigated whether antidepressant treatment causes any change in levels of this hormone or in sexual function. Premenopausal female patients aged 25-46 years (n = 52) with diagnosed major depression were included in this study as the patient group, and 25- to 46-year-old premenopausal women without depression (n = 30) were included as the control group. Serum testosterone and sex hormone-binding globulin (SHBG) levels were measured twice, before and after the antidepressant treatment. Bioavailable testosterone (cBT) levels were calculated using the assay results for total testosterone (TT), SHBG, and albumin according to the formulas of Vermeulen et al. Depression severity was measured using the 17-item Hamilton Depression Rating Scale, and sexual function was evaluated with the Arizona Sexual Experience Scale. The mean TT and cBT levels significantly increased in the patient group after the antidepressant treatment (P treatment TT and cBT levels were significantly lower in the patient group than in the control group (P treatment serum TT and cBT levels in the patient and control groups (P > 0.05). There were no significant differences among the groups in terms of SHBG level. The low testosterone levels in depressed women compared with women in the control group and the elevated levels post-pharmacotherapy suggest that testosterone may be involved in depression. © 2013 International Society for Sexual Medicine.

  20. 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

  1. Sex hormones and quantitative ultrasound parameters at the heel in men and women from the general population.

    Science.gov (United States)

    Pätzug, Konrad; Friedrich, Nele; Kische, Hanna; Hannemann, Anke; Völzke, Henry; Nauck, Matthias; Keevil, Brian G; Haring, Robin

    2017-12-01

    The present study investigates potential associations between liquid chromatography-mass spectrometry (LC-MS) measured sex hormones, dehydroepiandrosterone sulphate, sex hormone-binding globulin (SHBG) and bone ultrasound parameters at the heel in men and women from the general population. Data from 502 women and 425 men from the population-based Study of Health in Pomerania (SHIP-TREND) were used. Cross-sectional associations of sex hormones including testosterone (TT), calculated free testosterone (FT), dehydroepiandrosterone sulphate (DHEAS), androstenedione (ASD), estrone (E1) and SHBG with quantitative ultrasound (QUS) parameters at the heel, including broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were examined by analysis of variance (ANOVA) and multivariable quantile regression models. Multivariable regression analysis showed a sex-specific inverse association of DHEAS with SI in men (Beta per SI unit = - 3.08, standard error (SE) = 0.88), but not in women (Beta = - 0.01, SE = 2.09). Furthermore, FT was positively associated with BUA in men (Beta per BUA unit = 29.0, SE = 10.1). None of the other sex hormones (ASD, E1) or SHBG was associated with QUS parameters after multivariable adjustment. This cross-sectional population-based study revealed independent associations of DHEAS and FT with QUS parameters in men, suggesting a potential influence on male bone metabolism. The predictive role of DHEAS and FT as a marker for osteoporosis in men warrants further investigation in clinical trials and large-scale observational studies.

  2. The effect of endurance training on muscle strength in young, healthy men in relation to hormonal status.

    Science.gov (United States)

    Grandys, M; Majerczak, J; Duda, K; Zapart-Bukowska, J; Sztefko, K; Zoladz, J A

    2008-12-01

    The objective of this study was to establish the effect of moderate intensity endurance training on muscle strength in relation to hormonal changes in the body. Fifteen young, healthy men took part in 5 week endurance training performed on a cycloergometer. Before and after training program, exercise testing sessions were performed involving all participants. Training program significantly increased V(O2 max) (P<0.05) and time to fatigue at 50% of maximal voluntary isometric contraction (TTF 50% MVC), P<0.03, but it did not affect maximal voluntary isometric contraction (MVC). This was accompanied by an increase (P<0.001) in total plasma testosterone (T) and free testosterone (fT) concentrations, whereas a decrease in sex hormone-binding globulin (SHBG) (P<0.02), growth hormone (P<0.05), free triiodothyronine (P<0.001) and free thyroxine (P<0.02) concentrations was observed. No changes were found in plasma cortisol (C) and insulin-like growth factor-I (IGF-I) concentrations. Additionally, MVC was positively correlated to T/C, fT/C and IGF-I/C ratios after the training, whereas time to fatigue at 50% of MVC was closely positively correlated to the SHBG concentration, both before and after endurance training. We have concluded that moderate intensity endurance training resulting in a significant increase in V(O2 max), did not affect the MVC, but it significantly increased time to fatigue at 50% of MVC. This index of local muscular endurance was greater in subjects with higher concentration of SHBG, both before and after the training.

  3. Lower Serum DHEAS levels are associated with a higher degree of physical disability and depressive symptoms in middle-aged to older African American women

    Science.gov (United States)

    Haren, Matthew T.; Malmstrom, Theodore K.; Banks, William A.; Patrick, Ping; Miller, Douglas K.; Morley, John E.

    2007-01-01

    Background Changes in androgen levels and associations with chronic disease, physical and neuropsychological function and disability in women over the middle to later years of life are not well understood and have not been extensively studied in African-American women. Aims The present cross-sectional analysis reports such levels and associations in community dwelling, African American women aged 49 – 65 years from St. Louis, Missouri. Methods A home-based physical examination and a health status questionnaire were administered to randomly sampled women. Body composition (DEXA), lower limb and hand-grip muscle strength, physical and neuropsychological function and disability levels were assessed. Blood was drawn and assayed for total testosterone (T), sex hormone-binding globulin (SHBG), dehydroepiandrosterone-sulfate (DHEAS), oestradiol (E2), adiponectin, leptin, triglycerides, glucose, C-reactive protein (CRP) and cytokine receptors (sIL2r, sIL6r, sTNFr1 & sTNFr2). Multiple linear regression modelling was used to identify the best predictors of testosterone, DHEAS and Free Androgen Index (T/SHBG). Results Seventy-four percent of women were menopausal and a quarter of these were taking oestrogen therapy. DHEAS and E2 declined between the ages of 49 and 65 years, whereas total T, SHBG and FAI remained stable. Total T and DHEAS levels were strongly correlated. In this population sample there were no independent associations of either total T or FAI with indicators of functional limitations, disability or clinically relevant depressive symptoms. Unlike total T and FAI, lower DHEAS levels was independently associated with both higher IADL scores (indicating a higher degree of physical disability) and higher CESD scores (indicating a higher degree of clinically relevant depressive symptoms). Conclusion There is an age-related decline in serum DHEAS in African-American women. Lower DHEAS levels appear to be associated with a higher degree of physical disability and

  4. Increased cortisol in the cerebrospinal fluid of women with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Brundu, Benedetta; Loucks, Tammy L; Adler, Lauri J; Cameron, Judy L; Berga, Sarah L

    2006-04-01

    The proximate cause of functional hypothalamic amenorrhea (FHA) is reduced GnRH drive. The concomitant increase in circulating cortisol suggests that psychogenic stress plays an etiologic role, but others have argued for a strictly metabolic cause, such as undernutrition or excessive exercise. Indeed, our finding that the cerebrospinal fluid (CSF) concentration of CRH was not elevated in FHA cast doubt about the extent of hypothalamic-pituitary-adrenal activation in FHA and, therefore, we wondered whether central cortisol levels were elevated. We tested the null hypothesis that CSF cortisol levels would be comparable in FHA and eumenorrheic women (EW). The study is a cross-sectional comparison. The study was set in a general clinical research center at an academic medical center. Fifteen women with FHA who were of normal body weight and 14 EW participated. Blood samples were collected at 15-min intervals for 24 h, followed by procurement of 25 ml CSF. Cortisol, cortisol-binding globulin (CBG), and SHBG levels in blood and CSF were the main outcome measures. CSF cortisol concentrations were 30% greater when serum cortisol was 16% higher in FHA compared with EW. Circulating CBG, but not SHBG, was increased in FHA and, thus, the circulating free cortisol index was similar in FHA and EW. Because CBG and SHBG were nil in CSF, the increase in CSF cortisol in FHA was unbound. The hypothalamic-pituitary-adrenal axis is activated in FHA. The maintenance of CRH drive despite increased CSF cortisol indicates resistance to cortisol feedback inhibition. The mechanisms mediating feedback resistance likely involve altered hippocampal corticosteroid reception and serotonergic and GABAergic neuromodulation.

  5. Skyrmions with low binding energies

    Energy Technology Data Exchange (ETDEWEB)

    Gillard, Mike, E-mail: m.n.gillard@leeds.ac.uk; Harland, Derek, E-mail: d.g.harland@leeds.ac.uk; Speight, Martin, E-mail: speight@maths.leeds.ac.uk

    2015-06-15

    Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  6. Skyrmions with low binding energies

    International Nuclear Information System (INIS)

    Gillard, Mike; Harland, Derek; Speight, Martin

    2015-01-01

    Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values

  7. Skyrmions with low binding energies

    Directory of Open Access Journals (Sweden)

    Mike Gillard

    2015-06-01

    Full Text Available Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  8. 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.

  9. When is protein binding important?

    Science.gov (United States)

    Heuberger, Jules; Schmidt, Stephan; Derendorf, Hartmut

    2013-09-01

    The present paper is an ode to a classic citation by Benet and Hoener (2002. Clin Pharm Ther 71(3):115-121). The now classic paper had a huge impact on drug development and the way the issue of protein binding is perceived and interpreted. Although the authors very clearly pointed out the limitations and underlying assumptions for their delineations, these are too often overlooked and the classic paper's message is misinterpreted by broadening to cases that were not intended. Some members of the scientific community concluded from the paper that protein binding is not important. This was clearly not intended by the authors, as they finished their paper with a paragraph entitled: "When is protein binding important?" Misinterpretation of the underlying assumptions in the classic work can result in major pitfalls in drug development. Therefore, we revisit the topic of protein binding with the intention of clarifying when clinically relevant changes should be considered during drug development. Copyright © 2013 Wiley Periodicals, Inc.

  10. Identification and characterisation of the IgE-binding proteins 2S albumin and conglutin gamma in almond (Prunus dulcis) seeds.

    Science.gov (United States)

    Poltronieri, P; Cappello, M S; Dohmae, N; Conti, A; Fortunato, D; Pastorello, E A; Ortolani, C; Zacheo, G

    2002-06-01

    Almond proteins can cause severe anaphylactic reactions in susceptible individuals. The aim of this study was the identification of IgE-binding proteins in almonds and the characterisation of these proteins by N-terminal sequencing. Five sera were selected from individuals with a positive reaction to food challenge. Sodium dodecylsulphate-polyacrylamide gel electrophoresis and immunoblotting were performed on almond seed proteins. Purified IgE-binding proteins were tested for immunoblot inhibition with sera pre-incubated with extracts of hazelnut and walnut. N-terminal sequences of the 12-, 30- and 45-kD proteins were obtained. The 45- and 30-kD proteins shared the same N terminus, with 60% homology to the conglutin gamma heavy chain from lupine seed (Lupinus albus) and to basic 7S globulin from soybean (Glycine max). The sequences of the N-terminal 12-kD protein and of an internal peptide obtained by endoproteinase digestion showed good homology to 2S albumin from English walnut (Jug r 1). Immunoblot inhibition experiments were performed and IgE binding to almond 2S albumin and conglutin gamma was detected in the presence of cross-reacting walnut or hazelnut antigens. Two IgE-binding almond proteins were N-terminally sequenced and identified as almond 2S albumin and conglutin gamma. Localisation and conservation of IgE binding in a 6-kD peptide obtained by endoproteinase digestion of 2S albumin was shown. Copyright 2002 S. Karger AG, Basel

  11. 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...... profile of the integrin-linked kinase associated phosphatase (ILKAP), a member of the protein phosphatase 2C (PP2C) family. Phosphatases can potentially dephosphorylate these phosphopeptide substrates but, interestingly, performing the binding studies at 4 °C allowed efficient binding to phosphopeptides......, without the need for phosphopeptide mimics or phosphatase inhibitors. As no proven ILKAP substrates were available, we selected phosphopeptide substrates among known PP2Cδ substrates including the protein kinases: p38, ATM, Chk1, Chk2 and RSK2 and synthesized directly on PEGA solid supports through a BAL...

  12. 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...

  13. Do differences in age specific androgenic steroid hormone levels account for differing prostate cancer rates between Arabs and Caucasians?

    Science.gov (United States)

    Kehinde, Elijah O; Akanji, Abayomi O; Al-Hunayan, Adel; Memon, Anjum; Luqmani, Yunus; Al-Awadi, Khaleel A; Varghese, Ramani; Bashir, Abdul Aziz; Daar, Abdallah S

    2006-04-01

    Factors responsible for the low incidence of clinical prostate cancer in the Arab population remain unclear, but may be related to differences in androgenic steroid hormone metabolism between Arabs and other populations, especially as prostate cancer is believed to be androgen dependent. We therefore measured the levels of serum androgenic steroids and their binding proteins in Arab men and compared results obtained with values reported for Caucasian populations to determine if any differences could at least partially account for differences in incidence of prostate cancer rates between the two populations. Venous blood samples were obtained from 327 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-79 years. Samples were also obtained from 30 Arab men with newly diagnosed prostate cancer. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), derived free androgen index (FAI); adrenal C19 -steroids, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (ADT) were determined by chemiluminescent immunoassay. Age specific reference intervals, mean and median for each analyte were determined. Frequency distribution pattern for each hormone was plotted. The reference range for hormones with normal distribution was mean +/- 2SD and 2.5-97.5% for those with non-normal distribution. The mean serum levels of the hormones in Arab men with prostate cancer were compared with values in healthy age-matched Arab men. There was a significant decrease between the 21-29 years age group and the 70-79 years age group for TT (-38.77%), DHEAS (-70%), ADT (-36%) and FAI (-63.25%), and an increase for SHBG (+64%). The calculated reference ranges are TT (2.73-30.45 nmol/L), SHBG (6.45-65.67 nmol/L), FAI (14.51-180.34), DHEAS (0.9-11.0 micromol/L) and ADT (0.54-4.26 ng/mL). The mean TT, SHBG, DHEAS and ADT in Arab men were significantly lower than those reported for Caucasians especially in the 21-29 years age group. Arab men with

  14. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    , for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well...... as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context....

  15. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

    James, W.P.T.; Branch, W.J.; Southgate, D.A.T.

    1978-01-01

    Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids liberates the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity on the colon for calcium. (author)

  16. Testosterone levels and the genetic variation of sex hormone ...

    Indian Academy of Sciences (India)

    Lillian

    1Physiology and Hormones Department, Animal Health Research Institute, ... hormone-binging globulin (SHBG) that is the major transporter protein of sex ... genotypes, one of which is likely to be associated with low testosterone ..... sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium.

  17. Material Binding Peptides for Nanotechnology

    Directory of Open Access Journals (Sweden)

    Urartu Ozgur Safak Seker

    2011-02-01

    Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.

  18. 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.

  19. Anion binding in biological systems

    International Nuclear Information System (INIS)

    Feiters, Martin C; Meyer-Klaucke, Wolfram; Kostenko, Alexander V; Soldatov, Alexander V; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Kuepper, Frithjof C; Hollenstein, Kaspar; Locher, Kaspar P; Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R

    2009-01-01

    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 L 3 (2p 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.

  20. 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.

  1. Solute-vacancy binding in aluminum

    International Nuclear Information System (INIS)

    Wolverton, C.

    2007-01-01

    Previous efforts to understand solute-vacancy binding in aluminum alloys have been hampered by a scarcity of reliable, quantitative experimental measurements. Here, we report a large database of solute-vacancy binding energies determined from first-principles density functional calculations. The calculated binding energies agree well with accurate measurements where available, and provide an accurate predictor of solute-vacancy binding in other systems. We find: (i) some common solutes in commercial Al alloys (e.g., Cu and Mg) possess either very weak (Cu), or even repulsive (Mg), binding energies. Hence, we assert that some previously reported large binding energies for these solutes are erroneous. (ii) Large binding energies are found for Sn, Cd and In, confirming the proposed mechanism for the reduced natural aging in Al-Cu alloys containing microalloying additions of these solutes. (iii) In addition, we predict that similar reduction in natural aging should occur with additions of Si, Ge and Au. (iv) Even larger binding energies are found for other solutes (e.g., Pb, Bi, Sr, Ba), but these solutes possess essentially no solubility in Al. (v) We have explored the physical effects controlling solute-vacancy binding in Al. We find that there is a strong correlation between binding energy and solute size, with larger solute atoms possessing a stronger binding with vacancies. (vi) Most transition-metal 3d solutes do not bind strongly with vacancies, and some are even energetically strongly repelled from vacancies, particularly for the early 3d solutes, Ti and V

  2. A high frequency MspI RFLP at the human vitamin D binding protein (hDBP) locus

    Energy Technology Data Exchange (ETDEWEB)

    Ray, K; Cooke, N E [Univ. of Pennsylvania, Philadelphia (USA)

    1988-07-25

    A nearly full-length cDNA encoding the human vitamin D binding protein (hDBP), also known as Gc-globulin, was isolated from a human liver cDNA expression library. This 1.73 kb cDNA was digested with EcoRI and the 5{prime}, 140 bp fragment of the cDNA, subcloned into plasmid SP65 (phDBP140), was used as probe. MspI identifies a two allele polymorphism with either a band at 12 kb or a band at 5 kb. The frequency was estimated from a study of 24 unrelated North American Caucasians. The hDBP gene has been localized to chromosome 4 using a cDNA probe and a panel of rodent X human somatic cell hybrids. It was sublocalized to 4q11-q13 by in situ hybridization. Co-dominant autosomal segregation of the polymorphic alleles has been observed in two informative families (20 individuals). With overexposure of the autoradiograph two faint variant bands are seen at 17 kb and 13.5 kb which appear to cosegregate with the 12 kb band and the 5 kb band respectively.

  3. Effects of two doses of anti-T lymphocyte globulin-Fresenius given after full-match sibling stem cell transplantation in acute myeloblastic leukemia patients who underwent myeloablative fludarabine/busulfan conditioning.

    Science.gov (United States)

    Boga, Can; Yeral, Mahmut; Gereklioglu, Ciğdem; Asma, Suheyl; Maytalman, Erkan; Aytan, Pelin; Kozanoglu, Ilknur; Sariturk, Cagla; Ozdogu, Hakan

    2018-02-20

    Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F. This was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups. Although the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III-IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667-199.255; p = <.02). No patients developed rATG-F-related severe adverse events (Common Terminology Criteria grade 4 or 5). Dose difference of

  4. Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Soiffer, Robert J; Kim, Haesook T; McGuirk, Joseph; Horwitz, Mitchell E; Johnston, Laura; Patnaik, Mrinal M; Rybka, Witold; Artz, Andrew; Porter, David L; Shea, Thomas C; Boyer, Michael W; Maziarz, Richard T; Shaughnessy, Paul J; Gergis, Usama; Safah, Hana; Reshef, Ran; DiPersio, John F; Stiff, Patrick J; Vusirikala, Madhuri; Szer, Jeff; Holter, Jennifer; Levine, James D; Martin, Paul J; Pidala, Joseph A; Lewis, Ian D; Ho, Vincent T; Alyea, Edwin P; Ritz, Jerome; Glavin, Frank; Westervelt, Peter; Jagasia, Madan H; Chen, Yi-Bin

    2017-12-20

    Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

  5. Insulin binding to individual rat skeletal muscles

    International Nuclear Information System (INIS)

    Koerker, D.J.; Sweet, I.R.; Baskin, D.G.

    1990-01-01

    Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white [extensor digitorum longus (EDL), gastrocnemius] muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding

  6. The electrophilic lodi nation with 125 I/ 131 I of gamma globulin: Comparison between a solid-phase oxidizing agent (Iodogen), chloramine-T, iodine mono chloride and N-Bromo succinimide

    International Nuclear Information System (INIS)

    El-Wetery, A.S.; Ayyoub, S.; El-Mohty, A.A.; Raieh, M.; Ghonaim, A.Kh.

    1997-01-01

    A new available oxidizing agent, 1, 3, 4, 6-tetra chloro-3α, diphenyl glycoluril(iodogen) was compared with chloramine-T (Ch-T), Iodine-mono chloride (I Cl) and N-Bromo succinimide (NBS) in the radio-iodination of gamma-globulin (γ-G) with 'no-carrier-added' (nca) Na 131 I (T 1/2=8 d). In Phosphate and acetate buffer solution, the optimum reaction conditions with respect to PH, concentration of oxidizing agent, reaction time and concentration of γ-G were determined. The optimum conditions which were found require 100μ l of buffer (pH 7.4, 0.025 M), 500μg γ-G (0.003 μmol), (10-40) μg of oxidizing agent and the desired amount of carrier-free radioiodine. Highest radiochemical yield (>85-90%) were obtained at pH 7.4. Separation and identification of the labelled products were achieved by means of high performance liquid chromatography (HPLC) and thin layer chromatography (TLC). 8 figs., 1 tab

  7. Oral contraceptives increase insulin-like growth factor binding protein-1 concentration in women with polycystic ovarian disease.

    Science.gov (United States)

    Suikkari, A M; Tiitinen, A; Stenman, U H; Seppälä, M; Laatikainen, T

    1991-05-01

    Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. To investigate the effect of oral contraceptive (OC) pills, given for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in seven women with polycystic ovarian disease (PCOD) and in five healthy control subjects. Seven women with PCOD and five healthy control subjects. An oral glucose tolerance test (OGTT) was performed before and after treatment with OC. After treatment with OC, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentration increased in the women with PCOD as well as in the control subjects. The cumulative response of serum insulin to OGTT was larger in the women with PCOD than in the control subjects both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from basal level of 326 +/- 70 micrograms/L to 199 +/- 28 micrograms/L after treatment with OC in the women with PCOD, whereas no change was found in the control subjects (from 235 +/- 11 micrograms/L to 226 +/- 11 micrograms/L). Treatment with OC caused an increase of the mean basal IGFBP-1 concentration from 24 +/- 7 micrograms/L to 73 +/- 14 micrograms/L in the women with PCOD. This increase was constant during the OGTT. In the control subjects, treatment with OC did not result in any significant change in IGFBP-1 concentrations (from 44 +/- 11 micrograms/L to 61 +/- 9 micrograms/L). The combination of decreased total IGF-I concentration and increased IGFBP-1 concentration induced by OC may decrease ovarian androgen production in PCOD.

  8. 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.

  9. Focus on BMI and subclinical hypothyroidism in adolescent girls first examined for amenorrhea or oligomenorrhea. The emerging role of polycystic ovary syndrome.

    Science.gov (United States)

    Nezi, Markella; Christopoulos, Panagiotis; Paltoglou, George; Gryparis, Alexandros; Bakoulas, Vassilios; Deligeoroglou, Efthimios; Creatsas, George; Mastorakos, George

    2016-06-01

    Primary amenorrhea, oligomenorrhea and secondary amenorrhea are diagnosed commonly during adolescence. Weight aberrations are associated with menstrual disorders. Autoimmune thyroiditis is frequent during adolescence. In this study, the commonest clinical and hormonal characteristics of amenorrhea or oligomenorrhea during adolescence were investigated. In this cross-sectional study, one hundred and thirty-eight consecutive young patients presenting with amenorrhea or oligomenorrhea referred to an adolescent endocrinology and gynecology university clinic were studied. Clinical examination and an abdominal ultrasound were performed. Testosterone, free-testosterone, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), dehydroepiandrosterone sulfate (DHEA-S), 17-OH progesterone, sex hormone binding globulin (SHBG), Δ4-androstenedione (Δ4A), free androgen index (FAI), insulin, glucose, thyroid stimulating hormone (TSH), total thyroxine (T4) (TT4), free T4 (FT4), total triiodothyronine (T3) (TT3) and free T3 (FT3). Concentrations were measured in blood samples. Patients with primary and secondary amenorrhea presented more often with body mass index (BMI) 25 kg/m2, respectively. BMI values correlated positively with insulin (r=0.742) and glucose (r=0.552) concentrations and negatively with glucose/insulin ratio values (r=-0.54); BMI values and insulin concentrations correlated positively with FAI values (r=0.629 and r=0.399, respectively). In all patients, BMI values correlated positively and negatively with free testosterone (r=0.249) and SHBG (r=-0.24) concentrations, respectively. In patients with secondary amenorrhea insulin concentrations correlated negatively with SHBG concentrations (r=-0.75). In patients with oligomenorrhea BMI values correlated positively with insulin (r=0.490) and TSH (r=0.325) concentrations, and negatively with SHBG (r=-0.33) concentrations. Seventy-two percent, 21% and 7% of patients presented with

  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. Effect of Exercise on Serum Sex Hormones in Men: A 12-Month Randomized Clinical Trial

    Science.gov (United States)

    HAWKINS, VIVIAN N.; FOSTER-SCHUBERT, KAREN; CHUBAK, JESSICA; SORENSEN, BESS; ULRICH, CORNELIA M.; STANCYZK, FRANK Z.; PLYMATE, STEPHEN; STANFORD, JANET; WHITE, EMILY; POTTER, JOHN D.; MCTIERNAN, ANNE

    2011-01-01

    Purpose The effect of exercise on androgens in middle-aged to older men is poorly understood, and it could have implications for several aspects of health. This analysis was conducted to examine the effects of long-term aerobic exercise on serum sex hormones in middle-aged to older men. Methods One hundred two sedentary men, ages 40–75 yr, were randomly assigned to a 12-month exercise intervention or a control group (no change in activity). The combined facility- and home-based exercise program consisted of moderate/vigorous-intensity aerobic activity for 60 min·d−1, 6 d·wk−1. Serum concentrations of testosterone, free testosterone, dihydrotestosterone (DHT), 3α-androstanediol glucuronide (3α-Diol-G), estradiol, free estradiol, and sex hormone–binding globulin (SHBG) were measured at baseline, 3, and 12 months. Results Exercisers trained a mean of 370 min·wk−1 (102% of goal), with only two dropouts. Cardiopulmonary fitness (V̇O2max) increased 10.8% in exercisers and decreased by 1.8% in controls (P < 0.001). DHT increased 14.5% in exercisers versus 1.7% in controls at 3 months (P = 0.04); at 12 months, it remained 8.6% above baseline in exercisers versus a 3.1% decrease in controls (P = 0.03). SHBG increased 14.3% in exercisers versus 5.7% in controls at 3 months (P = 0.04); at 12 months, it remained 8.9% above baseline in exercisers versus 4.0% in controls (P = 0.13). There were significant trends toward increasing DHT and SHBG, with greater increases in V̇O2max at 3 and 12 months in exercisers. No statistically significant differences were observed for testosterone, free testosterone, 3α-Diol-G, estradiol, or free estradiol in exercisers versus controls. Conclusions A yearlong, moderate-intensity aerobic exercise program increased DHT and SHBG, but it had no effect on other androgens in middle-aged to older men. PMID:18202581

  12. Establishing the cut off values of androgen markers in the assessment of polycystic ovarian syndrome.

    Science.gov (United States)

    Nadaraja, R N D; Sthaneshwar, P; Razali, N

    2018-04-01

    Hyperandrogenism remains as one of the key features in Polycystic Ovarian Syndrome (PCOS) and can be assessed clinically or determined by biochemical assays. Hirsutism is the most common clinical manifestation of hyperandrogenism. The clinical assessment is subjected to wide variability due to poor interobserver agreement and multiple population factors such as ethnic variation, cosmetic procedures and genetic trait. The difficulty in resolving the androgen excess biochemically is due to a lack of consensus as to which serum androgen should be measured for the diagnosis of PCOS. The aim of the study was to compare and establish the diagnostic cut off value for different androgen biomarker for the diagnosis of PCOS. A total of 312 patients classified to PCOS (n = 164) and non PCOS (n = 148) cohorts were selected from the Laboratory Information System (LIS) based on serum total testosterone (TT) and sex hormone binding globulin (SHBG) from the period of 1st April 2015 to 31st March 2016. PCOS was diagnosed based on Rotterdam criteria. Clinical hyperandrogenism and ultrasound polycystic ovarian morphology were obtained from the clinical records. The other relevant biochemical results such as serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and albumin were also obtained from LIS. Free androgen index (FAI), calculated free testosterone (cFT) and calculated bioavailable testosterone (cBT) were calculated for these patients. Receiver Operating Characteristic (ROC) curve analysis were performed for serum TT, SHBG, FAI, cFT, cBT and LH: FSH ratio to determine the best marker to diagnose PCOS. All the androgen parameters (except SHBG) were significantly higher in PCOS patients than in control (pandrogen indices (FAI, cFT and cBT) showed good correlation with each other. Furthermore, cFT, FAI and calculated BT were shown to be more specific with higher positive likelihood ratio than measured androgen markers. Based on our study, the calculated testosterone

  13. 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

  14. DNA Binding Hydroxyl Radical Probes.

    Science.gov (United States)

    Tang, Vicky J; Konigsfeld, Katie M; Aguilera, Joe A; Milligan, Jamie R

    2012-01-01

    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.

  15. Asymmetric cation-binding catalysis

    DEFF Research Database (Denmark)

    Oliveira, Maria Teresa; Lee, Jiwoong

    2017-01-01

    The employment of metal salts is quite limited in asymmetric catalysis, although it would provide an additional arsenal of safe and inexpensive reagents to create molecular functions with high optical purity. Cation chelation by polyethers increases the salts' solubility in conventional organic...... 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...... highly enantioselective silylation reactions in polyether-generated chiral environments, and leading to a record-high turnover in asymmetric organocatalysis. This can lead to further applications by the asymmetric use of other inorganic salts in various organic transformations....

  16. The helical structure of DNA facilitates binding

    International Nuclear Information System (INIS)

    Berg, Otto G; Mahmutovic, Anel; Marklund, Emil; Elf, Johan

    2016-01-01

    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. (paper)

  17. Fundamental considerations in ski binding analysis.

    Science.gov (United States)

    Mote, C D; Hull, M L

    1976-01-01

    1. The static adjustment of a ski binding by hand or by available machines is only an adjustment and is neither a static nor a dynamic evaluation of the binding design. Bindings of different design with identical static adjustments will perform differently in environments in which the forces are static or dynamic. 2. The concept of binding release force is a useful measure of binding adjustment, but it is inappropriate as a criterion for binding evaluation. First, it does not direct attention toward the injury causing mechanism, strain, or displacement in the leg. Second, it is only part of the evaluation in dynamic problems. 3. The binding release decision in present bindings is displacement controlled. The relative displacement of the boot and ski is the system variable. For any specified relative displacement the binding force can be any of an infinite number of possibilities determined by the loading path. 4. The response of the leg-ski system to external impulses applied to the ski is independent of the boot-ski relative motion as long as the boot recenters quickly in the binding. Response is dependent upon the external impulse plus system inertia, damping and stiffness. 5. When tested under half sinusoidal forces applied to a test ski, all bindings will demonstrate static and impulse loading regions. In the static region the force drives the binding to a relative release displacement. In the impulse region the initial velocity of the ski drives the binding to a release displacement. 6. The transition between the static and impulse loading regions is determined by the binding's capacity to store and dissipate energy along the principal loading path. Increased energy capacity necessitates larger external impulses to produce release. 7. In all bindings examined to date, the transmitted leg displacement or strain at release under static loading exceeds leg strain under dynamic or impact loading. Because static loading is responsible for many injuries, a skier

  18. 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.

  19. 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...

  20. Bitopic Ligands and Metastable Binding Sites

    DEFF Research Database (Denmark)

    Fronik, Philipp; Gaiser, Birgit I; Sejer Pedersen, Daniel

    2017-01-01

    of orthosteric binding sites. Bitopic ligands have been employed to address the selectivity problem by combining (linking) an orthosteric ligand with an allosteric modulator, theoretically leading to high-affinity subtype selective ligands. However, it remains a challenge to identify suitable allosteric binding...... that have been reported to date, this type of bitopic ligands would be composed of two identical pharmacophores. Herein, we outline the concept of bitopic ligands, review metastable binding sites, and discuss their potential as a new source of allosteric binding sites....

  1. 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.

  2. 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

  3. New DNA-binding radioprotectors

    Science.gov (United States)

    Martin, Roger

    The normal tissue damage associated with cancer radiotherapy has motivated the development at Peter Mac of a new class of DNA-binding radioprotecting drugs that could be applied top-ically to normal tissues at risk. Methylproamine (MP), the lead compound, reduces radiation induced cell kill at low concentrations. For example, experiments comparing the clonogenic survival of transformed human keratinocytes treated with 30 micromolar MP before and dur-ing various doses of ionising radiation, with the radiation dose response for untreated cells, indicate a dose reduction factor (DRF) of 2. Similar survival curve experiments using various concentrations of MP, with parallel measurements of uptake of MP into cell nuclei, have en-abled the relationship between drug uptake and extent of radioprotection to be established. Radioprotection has also been demonstrated after systemic administration to mice, for three different endpoints, namely lung, jejunum and bone marrow (survival at 30 days post-TBI). The results of pulse radiolysis studies indicated that the drugs act by reduction of transient radiation-induced oxidative species on DNA. This hypothesis was substantiated by the results of experiments in which MP radioprotection of radiation-induced DNA double-strand breaks, assessed as -H2AX foci, in the human keratinocyte cell line. For both endpoints, the extent of radioprotection increased with MP concentration up to a maximal value. These results are consistent with the hypothesis that radioprotection by MP is mediated by attenuation of the extent of initial DNA damage. However, although MP is a potent radioprotector, it becomes cytotoxic at higher concentrations. This limitation has been addressed in an extensive program of lead optimisation and some promising analogues have emerged from which the next lead will be selected. Given the clinical potential of topical radioprotection, the new analogues are being assessed in terms of delivery to mouse oral mucosa. This is

  4. Outcomes of peripheral blood stem cell transplantation patients from HLA-mismatched unrelated donor with antithymocyte globulin (ATG)-Thymoglobulin versus ATG-Fresenius: a single-center study.

    Science.gov (United States)

    Huang, Wenrong; Zhao, Xiaoli; Tian, Yamin; Cao, Tingting; Li, Yanfen; Liu, Zhanxiang; Jing, Yu; Wang, Shuhong; Gao, Chunji; Yu, Li

    2015-02-01

    Although antithymocyte globulin (ATG) had been widely used in hematopoietic stem cell transplantation from unrelated donor due to its ability to prevent acute and chronic graft-versus-host disease (GVHD), the comparative efficacy and safety of ATG-Thymoglobulin (ATG-T) and ATG-Fresenius (ATG-F) in patients undergoing HLA-mismatched allogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) has not been evaluated. Retrospective analysis of patients who underwent HLA-mismatched UR-PBSCT between January 2003 and December 2013 and received pre-transplant ATG-T at a total dose of 10 mg/kg or ATG-F at a total dose of 20 mg/kg was performed. Patients who received ATG-T (n = 23) or ATG-F (n = 28) had similar baseline demographic, disease, and transplant characteristics. There were no significant between-groups differences in the probability of acute GVHD (P = 0.721) and chronic GVHD (P = 0.439). ATG-F was associated with nonsignificant trends toward higher disease-free survival at 3-year follow-up compared with ATG-T (45.7 ± 11.1 vs 61.3 ± 9.7 %, respectively, P = 0.07). A significantly greater proportion of ATG-T patients experienced high fever than ATG-F patients (P < 0.01) during ATG infusion. There was no difference in the rate of infection between the two treatment groups. There were less adverse effects comparing ATG-F with ATG-T. ATG-T at a total dose of 10 mg/kg and ATG-F at a total dose of 20 mg/kg had a similar clinical outcome in the setting of HLA-mismatched UR-PBSCT.

  5. 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.

  6. 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.

  7. 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.

  8. 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-...

  9. Identification of Glossina morsitans morsitans odorant binding ...

    African Journals Online (AJOL)

    Tsetse flies are vectors of trypanosome parasites, causative agents of Trypanosomiasis in humans and animals. Odorant Binding Proteins (OBPs) are critical in insect olfaction as they bind volatile odours from the environment and transport them to receptors within olfactory receptor neurons for processing providing critical ...

  10. 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)....

  11. 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...

  12. Binding of corroded ions to human saliva.

    Science.gov (United States)

    Mueller, H J

    1985-05-01

    Employing equilibrium dialysis, the binding abilities of Cu, Al, Co and Cr ions from corroded Cu-Al and Co-Cr dental casting alloys towards human saliva and two of its gel chromatographic fractions were determined. Results indicate that both Cu and Co bind to human saliva i.e. 0.045 and 0.027 mg/mg protein, respectively. Besides possessing the largest binding ability, Cu also possessed the largest binding capacity. The saturation of Cu binding was not reached up to the limit of 0.35 mg protein/ml employed in the tests, while Co reached full saturation at about 0.2 mg protein/ml. Chromium showed absolutely no binding to human saliva while Al ions did not pass through the dialysis membranes. Compared to the binding with solutions that were synthetically made up to contain added salivary-type proteins, it is shown that the binding to human saliva is about 1 order of magnitude larger, at least for Cu ions.

  13. Intentional binding of visual effects.

    Science.gov (United States)

    Ruess, Miriam; Thomaschke, Roland; Kiesel, Andrea

    2018-04-01

    When an action produces an effect, the effect is perceived earlier in time compared to a stimulus without preceding action. This temporal bias is called intentional binding (IB) and serves as an implicit measure of sense of agency. Typically, IB is investigated by presenting a rotating clock hand while participants execute an action and perceive a resulting tone. Participants are asked to estimate the time point of tone onset by referring to the clock hand position. This time point estimate is compared to a time point estimate of a tone in a condition in which the tone occurs without preceding action. Studies employing this classic clock paradigm employed auditory action effects. We modified this paradigm to investigate potential IB of visual action effects, and, additionally, to investigate how IB differs for visual action effects (Experiment 1) in comparison to auditory action effects (Experiment 2). Our results show that, like the IB of an auditory effect, the time point of a visual action effect is shifted toward the causing action, and that the size of the IB depends on the delay duration of the effect. Comparable to auditory action effects, earlier action effects showed stronger IB compared to later action effects. Yet overall IB of the visual effects was weaker than IB of the auditory effects. As IB is seen as an indicator of sense of agency, this may have important implications for the design of human-machine interfaces.

  14. Characterization of chlorophyll binding to LIL3.

    Science.gov (United States)

    Mork-Jansson, Astrid Elisabeth; Eichacker, Lutz Andreas

    2018-01-01

    The light harvesting like protein 3 (LIL 3) from higher plants, has been linked to functions in chlorophyll and tocopherol biosynthesis, photo-protection and chlorophyll transfer. However, the binding of chlorophyll to LIL3 is unclear. We present a reconstitution protocol for chlorophyll binding to LIL3 in DDM micelles. It is shown in the absence of lipids and carotenoids that reconstitution of chlorophyll binding to in vitro expressed LIL3 requires pre-incubation of reaction partners at room temperature. We show chlorophyll a but not chlorophyll b binding to LIL3 at a molar ratio of 1:1. Neither dynamic light scattering nor native PAGE, enabled a discrimination between binding of chlorophyll a and/or b to LIL3.

  15. (TH) diazepam binding to human granulocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bond, P.A.; Cundall, R.L.; Rolfe, B.

    1985-07-08

    (TH)-diazepam binds to sites on human granulocyte membranes, with little or no binding to platelets or lymphocytes. These (TH)-diazepam binding sites are of the peripheral type, being strongly inhibited by R05-4864 (Ki=6.23nM) but only weakly by clonazepam (Ki=14 M). Binding of (TH) diazepam at 0 is saturable, specific and stereoselective. Scatchard analysis indicates a single class of sites with Bmax of 109 +/- 17f moles per mg of protein and K/sub D/ of 3.07 +/- 0.53nM. Hill plots of saturation experiments gave straight lines with a mean Hill coefficient of 1.03 +/- 0.014. Binding is time dependent and reversible and it varies linearly with granulocyte protein concentration over the range 0.025-0.300 mg of protein. 11 references, 3 figures, 1 table.

  16. Factor VIIa binding and internalization in hepatocytes

    DEFF Research Database (Denmark)

    Hjortoe, G; Sorensen, B B; Petersen, L C

    2005-01-01

    The liver is believed to be the primary clearance organ for coagulation proteases, including factor VIIa (FVIIa). However, at present, clearance mechanisms for FVIIa in liver are unknown. To obtain information on the FVIIa clearance mechanism, we investigated the binding and internalization...... no effect. HEPG2 cells internalized FVIIa with a rate of 10 fmol 10(-5) cells h(-1). In contrast to HEPG2 cells, FVIIa binding to primary rat hepatocytes was completely independent of TF, and excess unlabeled FVIIa partly reduced the binding of 125I-FVIIa to rat hepatocytes. Further, compared with HEPG2...... cells, three- to fourfold more FVIIa bound to rat primary hepatocytes, and the bound FVIIa was internalized at a faster rate. Similar FVIIa binding and internalization profiles were observed in primary human hepatocytes. Plasma inhibitors had no effect on FVIIa binding and internalization in hepatocytes...

  17. 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

    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, plean 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.

  18. 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.

  19. 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 ...

  20. 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.

  1. Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

    International Nuclear Information System (INIS)

    Gangi Setty, Thanuja; Cho, Christine; Govindappa, Sowmya; Apicella, Michael A.; Ramaswamy, S.

    2014-01-01

    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

  2. Specific insulin binding in bovine chromaffin cells; demonstration of preferential binding to adrenalin-storing cells

    International Nuclear Information System (INIS)

    Serck-Hanssen, G.; Soevik, O.

    1987-01-01

    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 125 I-insulin was carried out at 15 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

  3. Human liver aldehyde dehydrogenase: coenzyme binding

    International Nuclear Information System (INIS)

    Kosley, L.L.; Pietruszko, R.

    1987-01-01

    The binding of [U- 14 C] NAD to mitochondrial (E2) and cytoplasmin(E1) aldehyde dehydrogenase was measured by gel filtration and sedimentation techniques. The binding data for NAD and (E1) yielded linear Scatchard plots giving a dissociation constant of 25 (+/- 8) uM and the stoichiometry of 2 mol of NAD bound per mol of E1. The binding data for NAD and (E2) gave nonlinear Scatchard plots. The binding of NADH to E2 was measured via fluorescence enhancement; this could not be done with E1 because there was no signal. The dissociation constant for E2 by this technique was 0.7 (+/- 0.4) uM and stoichiometry of 1.0 was obtained. The binding of [U- 14 C] NADH to (E1) and (E2) was also measured by the sedimentation technique. The binding data for (E1) and NADH gave linear Scatchard plots giving a dissociation constant of 13 (+/- 6) uM and the stoichiometry of 2.0. The binding data for NADH to (E2) gave nonlinear Scatchard plots. With (E1), the dissociation constants for both NAD and NADH are similar to those determined kinetically, but the stoichiometry is only half of that found by stopped flow technique. With (E2) the dissociation constant by fluorometric procedure was 2 orders of magnitude less than that from catalytic reaction

  4. Increased thyrotropin binding in hyperfunctioning thyroid nodules.

    Science.gov (United States)

    Müller-Gärtner, H W; Schneider, C; Bay, V; Tadt, A; Rehpenning, W; de Heer, K; Jessel, M

    1987-08-01

    The object of this study was to investigate TSH receptors in hyperfunctioning thyroid nodules (HFN). In HFN, obtained from seven patients, 125-I-TSH binding as determined by equilibrium binding analysis on particulate membrane preparations, was found to be significantly increased as compared with normal thyroid tissues (five patients; P less than 0.001). Scatchard analysis of TSH-binding revealed two kinds of binding sites for both normal thyroid tissue and HFN, and displayed significantly increased association constants of high- and low-affinity binding sites in HFN (Ka = 11.75 +/- 6.8 10(9) M-1, P less than 0.001 and Ka = 2.1 +/- 1.0 10(7) M-1, P less than 0.025; x +/- SEM) as compared with normal thyroid tissue (Ka = 0.25 +/- 0.06 10(9) M-1, Ka = 0.14 +/- 0.03 10(7) M-1; x +/- SEM). The capacity of the high-affinity binding sites in HFN was found to be decreased (1.8 +/- 1.1 pmol/mg protein, x +/- SEM) in comparison with normal thyroid tissue (4.26 +/- 1.27 pmol/mg protein; x +/- SEM). TSH-receptor autoradiography applied to cryostatic tissue sections confirmed increased TSH binding of the follicular epithelium in HFN. These data suggest that an increased affinity of TSH-receptor sites in HFN in iodine deficient areas may be an important event in thyroid autonomy.

  5. 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

  6. Effect of chickpea (Cicer arietinum L. germination on the major globulin content and in vitro digestibility Efeito da germinação de grão-de-bico (Cicer arietinum L. na globulina majoritária e digestibilidade in vitro

    Directory of Open Access Journals (Sweden)

    Guilherme Vanucchi Portari

    2005-12-01

    Full Text Available Chickpea seed germination was carried out over a period of 6 days. Little variation in the nitrogen and total globulin content was observed. The major globulin (11 S type showed higher variation after the 4th day of germination. The elution behaviour and distribution of the isolated major globulin fraction on Sepharose CL-6B chromatography showed little modification at the end of germination. On SDS-PAGE the peak eluted from Sepharose CL-6B showed changes in protein bands between 20 and 30 kDa and above 60 kDa, indicating protein degradation during the period. Proteolytic activity was detected in the albumin fraction of the seeds, which increased up to the fourth and then decreased up to the sixth day, when isolated chickpea total globulin and casein were used as substrates. Chickpea flour, isolated albumin and total globulin fractions did not show an increase for in vitro digestibility; however, the isolated major globulin was more susceptible to hydrolysis after germination.A germinação das sementes de grão-de-bico foi acompanhada por um período de 6 dias, no qual pequenas variações nos teores de nitrogênio e globulina total foram registradas. A globulina majoritária (tipo 11 S apresentou maiores variações após o quarto dia de germinação. A natureza e distribuição da fração globulina majoritária isolada na cromatografia em Sepharose CL-6B mostrou pequenas modificações ao final do período de germinação. A eletroforese em gel de poliacrilamida com dodecilssulfato de sódio do pico eluído na cromatografia em Sepharose CL-6B demonstra modificações nas bandas de proteínas entre os pesos moleculares de 20 e 30 kDa e acima de 60 kDa, indicando degradação protéica durante o período. Atividade proteolítica foi detectada na fração albumina da semente que aumentou até o quarto dia, seguido de queda até o sexto dia de germinação, quando da utilização de globulina total isolada da semente e caseína como substratos

  7. 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…

  8. 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

  9. Hardware device binding and mutual authentication

    Science.gov (United States)

    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.

  10. 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...... than 5 amino acids showed binding and a clear correlation with hydrophobicity was demonstrated for oligomers of different hydrophobic amino acids. Insertion of hydrophilic amino acids in a hydrophobic sequence diminished or abolished binding. In conclusion our results show that calreticulin has...

  11. Fatty Acid Binding Proteins in Prostate Cancer

    National Research Council Canada - National Science Library

    Jett, Marti

    2000-01-01

    We have shown that there is a distinct pattern of fatty acid binding protein (FAEP) expression in prostate cancer vs normal cells and that finding has be confirmed in patient samples of biopsy specimens...

  12. Bilirubin Binding Capacity in the Preterm Neonate.

    Science.gov (United States)

    Amin, Sanjiv B

    2016-06-01

    Total serum/plasma bilirubin (TB), the biochemical measure currently used to evaluate and manage hyperbilirubinemia, is not a useful predictor of bilirubin-induced neurotoxicity in premature infants. Altered bilirubin-albumin binding in premature infants limits the usefulness of TB in premature infants. In this article, bilirubin-albumin binding, a modifying factor for bilirubin-induced neurotoxicity, in premature infants is reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Exciton Binding Energy of Monolayer WS2

    Science.gov (United States)

    Zhu, Bairen; Chen, Xi; Cui, Xiaodong

    2015-03-01

    The optical properties of monolayer transition metal dichalcogenides (TMDC) feature prominent excitonic natures. Here we report an experimental approach to measuring the exciton binding energy of monolayer WS2 with linear differential transmission spectroscopy and two-photon photoluminescence excitation spectroscopy (TP-PLE). TP-PLE measurements show the exciton binding energy of 0.71 +/- 0.01 eV around K valley in the Brillouin zone.

  14. P-shell hyperon binding energies

    International Nuclear Information System (INIS)

    Koetsier, D.; Amos, K.

    1991-01-01

    A shell model for lambda hypernuclei has been used to determine the binding energy of the hyperon in nuclei throughout the p shell. Conventional (Cohen and Kurath) potential energies for nucleon-nucleon interactions were used with hyperon-nucleon interactions taken from Nijmegen one boson exchange potentials. The hyperon binding energies calculated from these potentials compare well with measured values. 7 refs., 2 figs

  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. 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.

  17. LIBRA: LIgand Binding site Recognition Application.

    Science.gov (United States)

    Hung, Le Viet; Caprari, Silvia; Bizai, Massimiliano; Toti, Daniele; Polticelli, Fabio

    2015-12-15

    In recent years, structural genomics and ab initio molecular modeling activities are leading to the availability of a large number of structural models of proteins whose biochemical function is not known. The aim of this study was the development of a novel software tool that, given a protein's structural model, predicts the presence and identity of active sites and/or ligand binding sites. The algorithm implemented by ligand binding site recognition application (LIBRA) is based on a graph theory approach to find the largest subset of similar residues between an input protein and a collection of known functional sites. The algorithm makes use of two predefined databases for active sites and ligand binding sites, respectively, derived from the Catalytic Site Atlas and the Protein Data Bank. Tests indicate that LIBRA is able to identify the correct binding/active site in 90% of the cases analyzed, 90% of which feature the identified site as ranking first. As far as ligand binding site recognition is concerned, LIBRA outperforms other structure-based ligand binding sites detection tools with which it has been compared. The application, developed in Java SE 7 with a Swing GUI embedding a JMol applet, can be run on any OS equipped with a suitable Java Virtual Machine (JVM), and is available at the following URL: http://www.computationalbiology.it/software/LIBRAv1.zip. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. 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.

  19. Radiation damage to DNA-binding proteins

    International Nuclear Information System (INIS)

    Culard, G.; Eon, S.; DeVuyst, G.; Charlier, M.; Spotheim-Maurizot, M.

    2003-01-01

    The DNA-binding properties of proteins are strongly affected upon irradiation. The tetrameric lactose repressor (a dimer of dimers) losses its ability to bind operator DNA as soon as at least two damages per protomer of each dimer occur. The monomeric MC1 protein losses its ability to bind DNA in two steps : i) at low doses only the specific binding is abolished, whereas the non-specific one is still possible; ii) at high doses all binding vanishes. Moreover, the DNA bending induced by MC1 binding is less pronounced for a protein that underwent the low dose irradiation. When the entire DNA-protein complexes are irradiated, the observed disruption of the complexes is mainly due to the damage of the proteins and not to that of DNA. The doses necessary for complex disruption are higher than those inactivating the free protein. This difference, larger for MC1 than for lactose repressor, is due to the protection of the protein by the bound DNA. The oxidation of the protein side chains that are accessible to the radiation-induced hydroxyl radicals seems to represent the inactivating damage

  20. 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.

  1. Recent improvements to Binding MOAD: a resource for protein–ligand binding affinities and structures

    Science.gov (United States)

    Ahmed, Aqeel; Smith, Richard D.; Clark, Jordan J.; Dunbar, James B.; Carlson, Heather A.

    2015-01-01

    For over 10 years, Binding MOAD (Mother of All Databases; http://www.BindingMOAD.org) has been one of the largest resources for high-quality protein–ligand complexes and associated binding affinity data. Binding MOAD has grown at the rate of 1994 complexes per year, on average. Currently, it contains 23 269 complexes and 8156 binding affinities. Our annual updates curate the data using a semi-automated literature search of the references cited within the PDB file, and we have recently upgraded our website and added new features and functionalities to better serve Binding MOAD users. In order to eliminate the legacy application server of the old platform and to accommodate new changes, the website has been completely rewritten in the LAMP (Linux, Apache, MySQL and PHP) environment. The improved user interface incorporates current third-party plugins for better visualization of protein and ligand molecules, and it provides features like sorting, filtering and filtered downloads. In addition to the field-based searching, Binding MOAD now can be searched by structural queries based on the ligand. In order to remove redundancy, Binding MOAD records are clustered in different families based on 90% sequence identity. The new Binding MOAD, with the upgraded platform, features and functionalities, is now equipped to better serve its users. PMID:25378330

  2. Recent improvements to Binding MOAD: a resource for protein-ligand binding affinities and structures.

    Science.gov (United States)

    Ahmed, Aqeel; Smith, Richard D; Clark, Jordan J; Dunbar, James B; Carlson, Heather A

    2015-01-01

    For over 10 years, Binding MOAD (Mother of All Databases; http://www.BindingMOAD.org) has been one of the largest resources for high-quality protein-ligand complexes and associated binding affinity data. Binding MOAD has grown at the rate of 1994 complexes per year, on average. Currently, it contains 23,269 complexes and 8156 binding affinities. Our annual updates curate the data using a semi-automated literature search of the references cited within the PDB file, and we have recently upgraded our website and added new features and functionalities to better serve Binding MOAD users. In order to eliminate the legacy application server of the old platform and to accommodate new changes, the website has been completely rewritten in the LAMP (Linux, Apache, MySQL and PHP) environment. The improved user interface incorporates current third-party plugins for better visualization of protein and ligand molecules, and it provides features like sorting, filtering and filtered downloads. In addition to the field-based searching, Binding MOAD now can be searched by structural queries based on the ligand. In order to remove redundancy, Binding MOAD records are clustered in different families based on 90% sequence identity. The new Binding MOAD, with the upgraded platform, features and functionalities, is now equipped to better serve its users. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Crystal structure of the botulinum neurotoxin type G binding domain: insight into cell surface binding.

    Science.gov (United States)

    Stenmark, Pål; Dong, Min; Dupuy, Jérôme; Chapman, Edwin R; Stevens, Raymond C

    2010-04-16

    Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-A 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. Copyright (c) 2010. Published by Elsevier Ltd.

  4. Structure-function relationships of Na+, K+, ATP, or Mg2+ binding and energy transduction in Na,K-ATPase

    DEFF Research Database (Denmark)

    Jorgensen, Peter L.; Pedersen, Per Amstrup

    2000-01-01

    Na,K-ATPase; Mutagenesis; Na+ binding; K+ binding; Tl+ binding; Mg2+ binding; ATP binding; Cation binding site; Energy transduction......Na,K-ATPase; Mutagenesis; Na+ binding; K+ binding; Tl+ binding; Mg2+ binding; ATP binding; Cation binding site; Energy transduction...

  5. Alpine ski bindings and injuries. Current findings.

    Science.gov (United States)

    Natri, A; Beynnon, B D; Ettlinger, C F; Johnson, R J; Shealy, J E

    1999-07-01

    In spite of the fact that the overall incidence of alpine ski injuries has decreased during the last 25 years, the incidence of serious knee sprains usually involving the anterior cruciate ligament (ACL) has risen dramatically since the late 1970s. This trend runs counter to a dramatic reduction in lower leg injuries that began in the early 1970s and to date has lowered the risk of injury below the knee by almost 90%. One of the primary design objectives of modern ski boots and bindings has been to protect the skier from tibia and ankle fractures. So, in that sense, they have done an excellent job. However, despite advances in equipment design, modern ski bindings have not protected the knee from serious ligament trauma. At the present time, we are unaware of any binding design, settings or function that can protect both the knee and lower extremities from serious ligament sprains. No innovative change in binding design appears to be on the horizon that has the potential to reduce the risk of these severe knee injuries. Indeed, only 1 study has demonstrated a means to help reduce this risk of serious knee sprains, and this study involved education of skiers, not ski equipment. Despite the inability of bindings to reduce the risk of severe knee injuries there can be no doubt that improvement in ski bindings has been the most important factor in the marked reduction in incidence of lower leg and ankle injuries during the last 25 years. The authors strongly endorse the application of present International Standards Organisation (ISO) and American Society for Testing and Materials (ASTM) standards concerning mounting, setting and maintaining modern 'state of the art' bindings.

  6. Dissociation of binding and learning processes.

    Science.gov (United States)

    Moeller, Birte; Frings, Christian

    2017-11-01

    A single encounter of a stimulus together with a response can result in a short-lived association between the stimulus and the response [sometimes called an event file, see Hommel, Müsseler, Aschersleben, & Prinz, (2001) Behavioral and Brain Sciences, 24, 910-926]. The repetition of stimulus-response pairings typically results in longer lasting learning effects indicating stimulus-response associations (e.g., Logan & Etherton, (1994) Journal of Experimental Psychology: Learning, Memory, and Cognition, 20, 1022-1050]. An important question is whether or not what has been described as stimulus-response binding in action control research is actually identical with an early stage of incidental learning (e.g., binding might be seen as single-trial learning). Here, we present evidence that short-lived binding effects can be distinguished from learning of longer lasting stimulus-response associations. In two experiments, participants always responded to centrally presented target letters that were flanked by response irrelevant distractor letters. Experiment 1 varied whether distractors flanked targets on the horizontal or vertical axis. Binding effects were larger for a horizontal than for a vertical distractor-target configuration, while stimulus configuration did not influence incidental learning of longer lasting stimulus-response associations. In Experiment 2, the duration of the interval between response n - 1 and presentation of display n (500 ms vs. 2000 ms) had opposing influences on binding and learning effects. Both experiments indicate that modulating factors influence stimulus-response binding and incidental learning effects in different ways. We conclude that distinct underlying processes should be assumed for binding and incidental learning effects.

  7. CaMELS: In silico prediction of calmodulin binding proteins and their binding sites.

    Science.gov (United States)

    Abbasi, Wajid Arshad; Asif, Amina; Andleeb, Saiqa; Minhas, Fayyaz Ul Amir Afsar

    2017-09-01

    Due to Ca 2+ -dependent binding and the sequence diversity of Calmodulin (CaM) binding proteins, identifying CaM interactions and binding sites in the wet-lab is tedious and costly. Therefore, computational methods for this purpose are crucial to the design of such wet-lab experiments. We present an algorithm suite called CaMELS (CalModulin intEraction Learning System) for predicting proteins that interact with CaM as well as their binding sites using sequence information alone. CaMELS offers state of the art accuracy for both CaM interaction and binding site prediction and can aid biologists in studying CaM binding proteins. For CaM interaction prediction, CaMELS uses protein sequence features coupled with a large-margin classifier. CaMELS models the binding site prediction problem using multiple instance machine learning with a custom optimization algorithm which allows more effective learning over imprecisely annotated CaM-binding sites during training. CaMELS has been extensively benchmarked using a variety of data sets, mutagenic studies, proteome-wide Gene Ontology enrichment analyses and protein structures. Our experiments indicate that CaMELS outperforms simple motif-based search and other existing methods for interaction and binding site prediction. We have also found that the whole sequence of a protein, rather than just its binding site, is important for predicting its interaction with CaM. Using the machine learning model in CaMELS, we have identified important features of protein sequences for CaM interaction prediction as well as characteristic amino acid sub-sequences and their relative position for identifying CaM binding sites. Python code for training and evaluating CaMELS together with a webserver implementation is available at the URL: http://faculty.pieas.edu.pk/fayyaz/software.html#camels. © 2017 Wiley Periodicals, Inc.

  8. Serum levels of insulin-like growth factor binding protein-1 and ovulatory responses to clomiphene citrate in women with polycystic ovarian disease.

    Science.gov (United States)

    Tiitinen, A E; Laatikainen, T J; Seppälä, M T

    1993-07-01

    To study the serum levels of insulin, insulin-like growth factor I (IGF-I), and insulin-like growth factor binding protein-1 (IGFBP-1) in relation to clomiphene citrate (CC) responsiveness in women with polycystic ovarian disease (PCOD). Prospective. PATIENTS, SETTING: Twenty-three women with PCOD admitted consecutively to the University Infertility Clinic, a tertiary referral center. Blood samples were taken at fasting state and during oral glucose tolerance test (OGTT) for the determination of insulin, IGF-I, and IGFBP-1. A dose of 50 to 200 mg/d CC was given for ovulation induction. With CC treatment, ovulation was achieved in 13 of 23 PCOD patients. The IGFBP-1 concentration was lower in CC nonresponders than in CC responders (20.5 +/- 4.0 ng/mL versus 41.0 +/- 8.5 ng/mL) (P PCOD patients. Lean CC nonresponders (n = 7) had almost threefold lower serum IGFBP-1 levels than lean CC responders (n = 6) (24.0 +/- 3.1 ng/mL versus 61.8 +/- 8.6 ng/mL) (P PCOD patients, the IGFBP-1 levels were low irrespective of CC responsiveness (14.8 +/- 8.0 ng/mL versus 16.7 +/- 7.2 ng/mL). The differences remained during OGTT. The concentrations of IGF-I, insulin, sex hormone-binding globulin, LH, FSH, and androgens showed no significant differences between CC responders and nonresponders. There was an inverse correlation between serum insulin and IGFBP-1 levels in obese PCOD patients, whereas this was not seen in lean patients. In lean PCOD patients, low serum IGFBP-1 concentration is related to CC unresponsiveness by a mechanism unrelated to insulin.

  9. Protein Binding Capacity of Different Forages Tannin

    Science.gov (United States)

    Yusiati, L. M.; Kurniawati, A.; Hanim, C.; Anas, M. A.

    2018-02-01

    Eight forages of tannin sources(Leucaena leucocephala, Arachis hypogaea, Mimosa pudica, Morus alba L, Swietenia mahagoni, Manihot esculenta, Gliricidia sepium, and Bauhinia purpurea)were evaluated their tannin content and protein binding capacity. The protein binding capacity of tannin were determined using precipitation of bovine serum albumin (BSA). Swietenia mahagonihas higest total tannin level and condensed tannin (CT) compared with other forages (P<0.01). The Leucaena leucocephala has highest hydrolysable tannin (HT) level (P<0.01). The total and condensed tannin content of Swietenia mahagoni were 11.928±0.04 mg/100 mg and 9.241±0.02mg/100mg dry matter (DM) of leaves. The hydrolysable tannin content of Leucaena leucocephala was 5.338±0.03 mg/100 mg DM of leaves. Binding capacity was highest in Swietenia mahagoni and Leucaena leucocephala compared to the other forages (P<0.01). The optimum binding of BSA to tannin in Leucaena leucocephala and Swietenia mahagoniwere1.181±0.44 and 1.217±0.60mg/mg dry matter of leaves. The present study reports that Swietenia mahagoni has highest of tannin content and Leucaena leucocephala and Swietenia mahagoni capacity of protein binding.

  10. 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 ...... 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.......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...... provisions’ which empower the municipalities to later ruling. This way of making plans postpones the actual regulation of an area (i.e. the planning permission) making it an individual ruling for instance at the application of building permits. Case studies show examples of this way of regulating an area...

  11. Assessment of the binding properties of granuloszint

    International Nuclear Information System (INIS)

    Schubiger, P.A.; Hasler, P.H.; Novak-Hofer, I.; Blaeuenstein, P.

    1989-01-01

    123 I-granuloszint (a murine monoclonal antibody - called AK-47 - against NCA-95 glycoprotein of granulocytes) has been proved to be a very convenient and successful radiopharmaceutical for visualizing infectious diseases. For a broad introduction in routine nuclear medicine it was necessary to optimize the labelling method and to determine in vitro exactly those biological and binding parameters which are relevant for an effective application in vivo. Binding to granulocytes has been shown to be specific and saturable (nonspecific binding about 10%) and is not via the Fc part of the antibody. The investigation of the binding properties of 125 I-labelled AK-47 gave the following results: Affinity constant 5x10 8 , 20,000-100,000 epitopes per granulocyte and an immunoreactivity of more than 90%. Labelling with 123 I reduced the immunoreactivity to 40%. The Lindmo method and immunoblotting are used as quality control to check the likely in vivo behaviour of the labelled antibody. There is a good correspondence between the results from the two methods. With our special labelling method and the different in vitro checks we have found a reliable way to control the production and to assure an optimal binding behaviour of 123 I-granuloszint. (orig.)

  12. Assessment of the binding properties of granuloszint

    Energy Technology Data Exchange (ETDEWEB)

    Schubiger, P.A.; Hasler, P.H.; Novak-Hofer, I.; Blaeuenstein, P.

    1989-09-01

    /sup 123/I-granuloszint (a murine monoclonal antibody - called AK-47 - against NCA-95 glycoprotein of granulocytes) has been proved to be a very convenient and successful radiopharmaceutical for visualizing infectious diseases. For a broad introduction in routine nuclear medicine it was necessary to optimize the labelling method and to determine in vitro exactly those biological and binding parameters which are relevant for an effective application in vivo. Binding to granulocytes has been shown to be specific and saturable (nonspecific binding about 10%) and is not via the Fc part of the antibody. The investigation of the binding properties of /sup 125/I-labelled AK-47 gave the following results: Affinity constant 5x10/sup 8/, 20,000-100,000 epitopes per granulocyte and an immunoreactivity of more than 90%. Labelling with /sup 123/I reduced the immunoreactivity to 40%. The Lindmo method and immunoblotting are used as quality control to check the likely in vivo behaviour of the labelled antibody. There is a good correspondence between the results from the two methods. With our special labelling method and the different in vitro checks we have found a reliable way to control the production and to assure an optimal binding behaviour of /sup 123/I-granuloszint. (orig.).

  13. New Mechanisms of Mercury Binding to Peat

    Science.gov (United States)

    Nagy, K. L.; Manceau, A.; Gasper, J. D.; Ryan, J. N.; Aiken, G. R.

    2007-12-01

    Mercury can be immobilized in the aquatic environment by binding to peat, a solid form of natural organic matter. Binding mechanisms can vary in strength and reversibility, and therefore will control concentrations of bioreactive mercury, may explain rates of mercury methylation, and are important for designing approaches to improve water quality using natural wetlands or engineered phytoremediation schemes. In addition, strong binding between mercury and peat is likely to result in the fixation of mercury that ultimately resides in coal. The mechanisms by which aqueous mercury at low concentrations reacts with both dissolved and solid natural organic matter remain incompletely understood, despite recent efforts. We have identified three distinct binding mechanisms of divalent cationic mercury to solid peats from the Florida Everglades using EXAFS spectroscopic data (FAME beamline, European Synchrotron Radiation Facility (ESRF)) obtained on experimental samples as compared to relevant references including mercury-bearing solids and mercury bound to various organic molecules. The proportions of the three molecular configurations vary with Hg concentration, and two new configurations that involve sulfur ligands occur at Hg concentrations up to about 4000 ppm. The binding mechanism at the lowest experimental Hg concentration (60-80 ppm) elucidates published reports on the inhibition of metacinnabar formation in the presence of Hg-bearing solutions and dissolved natural organic matter, and also, the differences in extent of mercury methylation in distinct areas of the Florida Everglades.

  14. 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.

  15. Human serum albumin binding of certain antimalarials

    Science.gov (United States)

    Marković, Olivera S.; Cvijetić, Ilija N.; Zlatović, Mario V.; Opsenica, Igor M.; Konstantinović, Jelena M.; Terzić Jovanović, Nataša V.; Šolaja, Bogdan A.; Verbić, Tatjana Ž.

    2018-03-01

    Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site. Fluorescence quenching at three temperatures (20, 25, and 37 °C) was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. The enthalpy and entropy changes upon sulphur-containing compound-HSA interactions were calculated using Van't Hoff equation. Positive values of enthalpy and entropy changes indicate that non-specific, hydrophobic interactions are the main contributors to HSA-compound interaction. Molecular docking and calculated lipophilicity descriptors indicate the same, pointing out that the increased lipophilicity of sulphur-containing compounds might be a reason for their better binding to HSA. Obtained results might contribute to design of novel derivatives with improved pharmacokinetic properties and drug efficacy.

  16. 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...... a water-phase shuttle of monomers mediates such transfers. We have used our method based upon the use of albumin-filled red cell ghosts as a dispersed biological "reference binder" to measure the water-phase concentrations of anandamide. These concentrations were measured in buffer (pH 7.3) in equilibrium...... that BSA has one high-affinity binding site for anandamide at all four temperatures. The free energy of anandamide binding (¿G) is calculated to -43.05 kJ mol with a large enthalpy (¿H ) contribution of -42.09 kJ mol. Anandamide has vasodilator activity, and the binding to albumin may mediate its transport...

  17. Binding of Fidarestat Stereoisomers with Aldose Reductase

    Directory of Open Access Journals (Sweden)

    Dae-Sil Lee

    2006-11-01

    Full Text Available The stereospecificity in binding to aldose reductase (ALR2 of two fidarestat {6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carboxamide} stereoisomers [(2S,4Sand (2R,4S] has been investigated by means of molecular dynamics simulations using freeenergy integration techniques. The difference in the free energy of binding was found to be2.0 ± 1.7 kJ/mol in favour of the (2S,4S-form, in agreement with the experimentalinhibition data. The relative mobilities of the fidarestats complexed with ALR2 indicate alarger entropic penalty for hydrophobic binding of (2R,4S-fidarestat compared to (2S,4S-fidarestat, partially explaining its lower binding affinity. The two stereoisomers differmainly in the orientation of the carbamoyl moiety with respect to the active site and rotationof the bond joining the carbamoyl substituent to the ring. The detailed structural andenergetic insights obtained from out simulations allow for a better understanding of thefactors determining stereospecific inhibitor-ALR2 binding in the EPF charges model.

  18. 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).

  19. Binding of ethidium to the nucleosome core particle. 2. Internal and external binding modes

    International Nuclear Information System (INIS)

    McMurray, C.T.; Small, E.W.; van Holde, K.E.

    1991-01-01

    The authors have previously reported that the binding of ethidium bromide to the nucleosome core particle results in a stepwise dissociation of the structure which involves the initial release of one copy each of H2A and H2B. In this report, they have examined the absorbance and fluorescence properties of intercalated and outside bound forms of ethidium bromide. From these properties, they have measured the extent of external, electrostatic binding of the dye versus internal, intercalation binding to the core particle, free from contribution by linker DNA. They have established that dissociation is induced by the intercalation mode of binding to DNA within the core particle DNA, and not by binding to the histones or by nonintercalative binding to DNA. The covalent binding of [ 3 H]-8-azidoethidium to the core particle clearly shows that < 1.0 adduct is formed per histone octamer over a wide range of input ratios. Simultaneously, analyses of steady-state fluorescence enhancement and fluorescence lifetime data from bound ethidium complexes demonstrate extensive intercalation binding. Combined analyses from steady-state fluorescence intensity with equilibrium dialysis or fluorescence lifetime data revealed that dissociation began when ∼14 ethidium molecules are bound by intercalation to each core particle and < 1.0 nonintercalated ion pair was formed per core particle

  20. 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 of ...

  1. Quantification of Cooperativity in Heterodimer-DNA Binding Improves the Accuracy of Binding Specificity Models*

    Science.gov (United States)

    Isakova, Alina; Berset, Yves; Hatzimanikatis, Vassily; Deplancke, Bart

    2016-01-01

    Many transcription factors (TFs) have the ability to cooperate on DNA elements as heterodimers. Despite the significance of TF heterodimerization for gene regulation, a quantitative understanding of cooperativity between various TF dimer partners and its impact on heterodimer DNA binding specificity models is still lacking. Here, we used a novel integrative approach, combining microfluidics-steered measurements of dimer-DNA assembly with mechanistic modeling of the implicated protein-protein-DNA interactions to quantitatively interrogate the cooperative DNA binding behavior of the adipogenic peroxisome proliferator-activated receptor γ (PPARγ):retinoid X receptor α (RXRα) heterodimer. Using the high throughput MITOMI (mechanically induced trapping of molecular interactions) platform, we derived equilibrium DNA binding data for PPARγ, RXRα, as well as the PPARγ:RXRα heterodimer to more than 300 target DNA sites and variants thereof. We then quantified cooperativity underlying heterodimer-DNA binding and derived an integrative heterodimer DNA binding constant. Using this cooperativity-inclusive constant, we were able to build a heterodimer-DNA binding specificity model that has superior predictive power than the one based on a regular one-site equilibrium. Our data further revealed that individual nucleotide substitutions within the target site affect the extent of cooperativity in PPARγ:RXRα-DNA binding. Our study therefore emphasizes the importance of assessing cooperativity when generating DNA binding specificity models for heterodimers. PMID:26912662

  2. Quantification of Cooperativity in Heterodimer-DNA Binding Improves the Accuracy of Binding Specificity Models.

    Science.gov (United States)

    Isakova, Alina; Berset, Yves; Hatzimanikatis, Vassily; Deplancke, Bart

    2016-05-06

    Many transcription factors (TFs) have the ability to cooperate on DNA elements as heterodimers. Despite the significance of TF heterodimerization for gene regulation, a quantitative understanding of cooperativity between various TF dimer partners and its impact on heterodimer DNA binding specificity models is still lacking. Here, we used a novel integrative approach, combining microfluidics-steered measurements of dimer-DNA assembly with mechanistic modeling of the implicated protein-protein-DNA interactions to quantitatively interrogate the cooperative DNA binding behavior of the adipogenic peroxisome proliferator-activated receptor γ (PPARγ):retinoid X receptor α (RXRα) heterodimer. Using the high throughput MITOMI (mechanically induced trapping of molecular interactions) platform, we derived equilibrium DNA binding data for PPARγ, RXRα, as well as the PPARγ:RXRα heterodimer to more than 300 target DNA sites and variants thereof. We then quantified cooperativity underlying heterodimer-DNA binding and derived an integrative heterodimer DNA binding constant. Using this cooperativity-inclusive constant, we were able to build a heterodimer-DNA binding specificity model that has superior predictive power than the one based on a regular one-site equilibrium. Our data further revealed that individual nucleotide substitutions within the target site affect the extent of cooperativity in PPARγ:RXRα-DNA binding. Our study therefore emphasizes the importance of assessing cooperativity when generating DNA binding specificity models for heterodimers. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. 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. © 2014, The American College of Clinical Pharmacology.

  4. Bones and Crohn's: Estradiol deficiency in men with Crohn's disease is not associated with reduced bone mineral density

    Directory of Open Access Journals (Sweden)

    Boehm BO

    2008-10-01

    Full Text Available Abstract Background Reduced bone mineral density (BMD and osteoporosis are frequent in Crohn's disease (CD, but the underlying mechanisms are still not fully understood. Deficiency of sex steroids, especially estradiol (E2, is an established risk factor in postmenopausal osteoporosis. Aim To assess if hormonal deficiencies in male CD patients are frequent we investigated both, sex steroids, bone density and bone metabolism markers. Methods 111 male CD patients underwent osteodensitometry (DXA of the spine (L1–L4. Disease related data were recorded. Disease activity was estimated using Crohn's disease activity index (CDAI. Testosterone (T, dihydrotestosterone (DHT, estradiol (E2, sex hormone binding globulin (SHBG, Osteocalcin and carboxyterminal cross-linked telopeptids (ICTP were measured in 111 patients and 99 age-matched controls. Results Patients had lower T, E2 and SHBG serum levels (p 10 g had lower BMD. 32 (28.8% patients showed osteoporosis, 55 (49.5% osteopenia and 24 (21.6% had normal BMD. Patients with normal or decreased BMD showed no significant difference in their hormonal status. No correlation between markers of bone turnover and sex steroids could be found. ICTP was increased in CD patients (p Conclusion We found an altered hormonal status – i.e. E2 and, to a lesser extent T deficiency – in male CD patients but failed to show an association to bone density or markers of bone turnover. The role of E2 in the negative skeletal balance in males with CD, analogous to E2 deficiency in postmenopausal females, deserves further attention.

  5. Maca reduces blood pressure and depression, in a pilot study in postmenopausal women.

    Science.gov (United States)

    Stojanovska, L; Law, C; Lai, B; Chung, T; Nelson, K; Day, S; Apostolopoulos, V; Haines, C

    2015-02-01

    Lepidium meyenii (Maca) has been used for centuries for its fertility-enhancing and aphrodisiac properties. In an Australian study, Maca improved anxiety and depressive scores. The effects of Maca on hormones, lipids, glucose, serum cytokines, blood pressure, menopausal symptoms and general well-being in Chinese postmenopausal women were evaluated. A randomized, double-blind, placebo-controlled, cross-over study was conducted in 29 postmenopausal Hong Kong Chinese women. They received 3.3 g/day of Maca or placebo for 6 weeks each, in either order, over 12 weeks. At baseline, week 6 and week 12, estradiol, follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), thyroid stimulating hormone (TSH), full lipid profiles, glucose and serum cytokines were measured. The Greene Climacteric, SF-36 Version 2, Women's Health Questionnaire and Utian Quality of Life Scales were used to assess the severity of menopausal symptoms and health-related quality of life. There were no differences in estradiol, FSH, TSH, SHBG, glucose, lipid profiles and serum cytokines amongst those who received Maca as compared to the placebo group; however, significant decreases in diastolic blood pressure and depression were apparent after Maca treatment. Maca did not exert hormonal or immune biological action in the small cohort of patients studied; however, it appeared to reduce symptoms of depression and improve diastolic blood pressure in Chinese postmenopausal women. Although results are comparable to previous similar published studies in postmenopausal women, there might be a cultural difference among the Chinese postmenopausal women in terms of symptom reporting.

  6. Associations between brominated flame retardants in house dust and hormone levels in men

    International Nuclear Information System (INIS)

    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-, 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

  7. Plasma Testosterone and the Course of Major Depressive Disorder in Older Men and Women.

    Science.gov (United States)

    Giltay, Erik J; van der Mast, Roos C; Lauwen, Esther; Heijboer, Annemieke C; de Waal, Margot W M; Comijs, Hannie C

    2017-04-01

    To investigate associations between testosterone levels and major depressive disorder (MDD) in older men and women. In a cross-sectional, 2-year prospective analyses within the Netherlands Study on Depression in Older persons cohort study, 469 participants comprised 350 patients with MDD and 119 nondepressed participants in the comparison group (mean age 70.5 ± 7.3 years; 166 [35.4%] men). MDD was assessed by the Composite International Diagnostic Interview. Baseline plasma total testosterone and sex hormone binding globulin (SHBG) were assessed to calculate free testosterone. The Inventory of Depressive Symptomatology was assessed every 6 months. Whereas SHBG levels did not differ between the depressed/nondepressed groups (F(1,149) = 0.075, p = 0.78), men with MDD had lower mean total and free testosterone levels than the comparison group in the multivariate adjusted analyses (F(1,150) = 7.249, p = 0.008, Cohen's d = 0.51; and F(1,149) = 8.548, p = 0.004 Cohen's d = 0.55, respectively). This could be ascribed to lower testosterone in men with "pure" MDD and not in men with MDD and comorbid anxiety. Nine men (5.4%) had a total testosterone level men (using all five measurement points during follow-up) baseline free testosterone was inversely associated with depression severity in the adjusted analyses (β = -0.15, t(151) = -2.15, p = 0.03). Testosterone levels were lower in men with MDD compared with healthy men after adjustment for confounders, such as body mass index. No significant associations were found in women. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  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. 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.

  10. Endurance training of moderate intensity increases testosterone concentration in young, healthy men.

    Science.gov (United States)

    Grandys, M; Majerczak, J; Duda, K; Zapart-Bukowska, J; Kulpa, J; Zoladz, J A

    2009-07-01

    The aim of this study was to investigate the effect of short-term, moderate intensity and low volume endurance training on gonadal hormone profile in untrained men. Fifteen young, healthy men performed an endurance training of 5-week duration on a cycle ergometer. Before and after the exercise program all participants completed a maximal incremental test. Concentration of testosterone (T), sex hormone-binding globulin (SHBG) and cortisol (C) as well as blood morphology were determined in venous blood samples at rest both before and after the training. The training program resulted in 3.7% improvement of maximal oxygen uptake (VO(2max)) and 8.2% improvement of power output reached at VO(2max) (PO (max)). This was accompanied by significant increase in T (from 18.84+/-5.73 nmol.l(-1) to 22.03+/-6.61 nmol.l(-1), p = 0.0004) and calculated fT concentration (from 374+/-116 pmol.l(-1) to 470+/-153 pmol.l(-1), p = 0.00005). Moreover, the training caused a significant decrease in SHBG concentration (from 34.45+/-11.26 nmol.l(-1) to 31.95+/-10.40 nmol.l(-1), p = 0.01), whereas no significant changes were found in the cortisol concentration (334+/-138 nmol.l(-1) vs. 367+/-135 nmol.l(-1) for pre- and post-training measures, respectively, p = 0.50) and T/C and fT/C ratios. We have concluded that short-term, moderate intensity and low volume endurance training can significantly increase testosterone concentration in previously untrained men.

  11. Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome.

    Science.gov (United States)

    Jedel, Elizabeth; Gustafson, Deborah; Waern, Margda; Sverrisdottir, Yrsa Bergmann; Landén, Mikael; Janson, Per Olof; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

    2011-11-01

    Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). Circulating concentrations of testosterone (T) (P=0.026), free T (FT) (P=0.025), and androstane-3α 17β-diol-3glucuronide (3G) (P=0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S≥11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Body composition and circulating estradiol are the main bone density predictors in healthy young and middle-aged men.

    Science.gov (United States)

    Bilha, S C; Branisteanu, D; Buzduga, C; Constantinescu, D; Cianga, P; Anisie, E; Covic, A; Ungureanu, M C

    2018-01-16

    Current fracture risk assessment options in men call for improved evaluation strategies. Recent research directed towards non-classic bone mass determinants have often yielded scarce and conflicting results. We aimed at investigating the impact of novel potential bone mass regulators together with classic determinants of bone status in healthy young and middle-aged men. Anthropometric measurements, all-site bone mineral density (BMD) and body composition parameters assessed by dual-energy X-ray absorptiometry and also serum concentrations of (1) the adipokines leptin and resistin, (2) vitamin D and parathormone (PTH), (3) sex hormone binding globulin (SHBG), total testosterone and estradiol (free testosterone was also calculated) and (4) C-terminal telopeptide of type I collagen (CTx) were obtained from 30 apparently healthy male volunteers aged 20-65 years enrolled in this cross-sectional study. Only lean mass (LM) and total estradiol independently predicted BMD in men in multiple regression analysis, together explaining 49% (p ≤ 0.001) of whole-body BMD variance. Hierarchical regression analysis with whole-body BMD as outcome variable demonstrated that the body mass index (BMI) beta coefficient became nonsignificant when LM was added to the model. Adipokines, fat parameters, testosterone (total and free), SHBG, PTH and vitamin D were not independently associated with BMD or CTx. The present study shows that LM and sex hormones-namely estradiol-are the main determinants of bone mass in young and middle-aged men. The effects of BMI upon BMD seem to be largely mediated by LM. Lifestyle interventions should focus on preserving LM in men for improved bone outcomes.

  13. Effects of selenium on short-term control of hyperthyroidism due to Graves' disease treated with methimazole: results of a randomized clinical trial.

    Science.gov (United States)

    Leo, M; Bartalena, L; Rotondo Dottore, G; Piantanida, E; Premoli, P; Ionni, I; Di Cera, M; Masiello, E; Sassi, L; Tanda, M L; Latrofa, F; Vitti, P; Marcocci, C; Marinò, M

    2017-03-01

    In spite of previous conflicting results, an adjuvant role of selenium in the treatment of Graves' disease (GD) hyperthyroidism has been proposed. To address this issue, a randomized clinical trial was carried out aimed at investigating whether selenium is beneficial on the short-term control of GD hyperthyroidism treated with methimazole (MMI). Thirty newly diagnosed hyperthyroid GD patients were randomly assigned to treatment with: (i) MMI or (ii) MMI plus selenium. Primary outcomes were: control of hyperthyroidism and clinical and biochemi