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Sample records for binding globulin cbg

  1. 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)

  2. 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.

  3. 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,

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

    Directory of Open Access Journals (Sweden)

    Nicolette Verhoog

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

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

    Science.gov (United States)

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

    2014-03-01

    Corticosteroid binding globulin (CBG) is a glycoprotein synthesized in liver and secreted in the blood where it binds with a high affinity but low capacity glucocorticoid hormones, cortisol in humans and corticosterone in laboratory rodents. In mammals, 95% of circulating glucocorticoids are bound to either CBG (80%) or albumin (15%) and only the 5% free fraction is able to enter the brain. During stress, the concentration of glucocorticoids rises significantly and the free fraction increases even more because CBG becomes saturated. However, glucocorticoids unbound to CBG are cleared from the blood more quickly. Our studies on mice totally devoid of CBG (Cbg k.o.) showed that during stress these mutant mice display a lower rise of glucocorticoids than the wild-type controls associated with altered emotional reactivity. These data suggested that CBG played a role in the fast actions of glucocorticoids on behavior. Further analyses demonstrated that stress-induced memory retrieval impairment, an example of the fast action of glucocorticoids on the brain is abolished in the Cbg k.o. mice. This effect of stress on memory retrieval could be restored in the Cbg k.o. mice by infusing corticosterone directly in the hippocampus. The mechanisms explaining these effects involved an increased clearance but no difference in corticosterone production. Thus, CBG seems to have an important role in maintaining in blood a glucocorticoid pool that will be able to access the brain for the fast effects of glucocorticoids. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. 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

  7. 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.

  8. Pyrexia's effect on the CBG-cortisol thermocouple, rather than CBG cleavage, elevates the acute free cortisol response to TNF-α in humans

    DEFF Research Database (Denmark)

    Nenke, Marni Anne; Nielsen, Signe Tellerup; Lehrskov, Louise Lang

    2017-01-01

    Corticosteroid-binding globulin (CBG) cleavage promotes local cortisol delivery in inflammation. Enzymatic cleavage of high-affinity CBG to low-affinity CBG (haCBG to laCBG) occurs at inflammatory sites and is now measurable in vivo; however, the time kinetics of haCBG depletion following...... an inflammatory stimulus is unknown. Hence our aim was to determine the immediate effect of the key pro-inflammatory cytokine TNF-α on CBG levels and cleavage. We performed a crossover study of 12 healthy males receiving a TNF-α versus saline infusion, measuring total CBG, haCBG, laCBG and free and total cortisol...... hourly for 6 h. There was no change in total CBG or haCBG levels in the first 6 h of inflammation between the groups, suggesting that CBG cleavage is not activated nor is hepatic CBG production affected by TNF-α in this time frame. There was an early increase in the ratio of free:total cortisol...

  9. 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....

  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. 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.

  12. Evidence of Reduced CBG Cleavage in Abdominal Obesity: A Potential Factor in Development of the Metabolic Syndrome.

    Science.gov (United States)

    Nenke, M A; Lewis, J G; Rankin, W; Torpy, D J

    2016-08-01

    Corticosteroid-binding globulin (CBG) is involved in the regulation of cortisol delivery. Neutrophil elastase-mediated cleavage of high to low affinity CBG (haCBG to laCBG) induces cortisol release at inflammatory sites. Past studies have shown reduced CBG in obesity, an inflammatory state, particularly in central adiposity/metabolic syndrome. We performed an observational, cross-sectional study of the effects of obesity, age and sex on ha/laCBG in 100 healthy volunteers. Total and haCBG levels were 11% higher in women but did not vary with age or menopausal status. Total CBG levels were lower with increased body weight and waist circumference; laCBG levels were lower with increased body weight, waist circumference, body mass index and body fat; higher haCBG levels were seen with increased body fat. The relation between CBG and adiposity appeared to be driven predominantly by the metabolic syndrome group. The results suggest reduced CBG cleavage in central obesity, possibly contributing to the characteristic inflammatory phenotype of the central obesity and metabolic syndrome. The mechanism of gender differences in CBG levels is unclear. © Georg Thieme Verlag KG Stuttgart · New York.

  13. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... and Iron-binding Capacity (TIBC, UIBC) Trichomonas Testing Triglycerides Troponin Tryptase Tumor Markers Uric Acid Urinalysis Urine ... Syndrome CME. Medscape From Nature Clinical Practice Endocrinology & Metabolism [On-line information]. Available online at http://www. ...

  14. 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.

  15. 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.

  16. 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

  17. Adiponectin And Sex Hormone-Binding Globulin In Preeclampsia ...

    African Journals Online (AJOL)

    Adiponectin And Sex Hormone-Binding Globulin In Preeclampsia: Relationship To Insulin Resistance. ... this is a leading cause of maternal and fetal morbidity and mortality. The present study was ... Also the fasting levels of glucose and insulin were significantly higher in PE than normotensive pregnant women. There was ...

  18. The effects of neonatal handling on adrenocortical responsiveness, morphological development and corticosterone binding globulin in nestling American kestrels (Falco sparverius).

    Science.gov (United States)

    Whitman, Buddy A; Breuner, Creagh W; Dufty, Alfred M

    2011-06-01

    Early developmental experiences play an important role in development of the adult phenotype. We investigated the effects of neonatal handling on the hypothalamic-pituitary-adrenal axis in a free-living avian species, the American kestrel (Falco sparverius). In the handled group (H), kestrel chicks were handled for 15 min/day from hatching until 26 days of age, after which time blood samples were collected for analysis of adrenal responsiveness and corticosterone binding globulin (CBG) levels. The non-handled control group (NH) was left undisturbed until 26 days of age when blood samples were collected and analyzed as above. Handled and NH kestrels did not differ in body condition index. Both total corticosterone (CORT) and CBG capacity were dampened significantly in H kestrels. However, free CORT did not differ between the two groups. In addition, hormone challenges of corticotropin releasing factor and adrenocorticotropin hormone were compared to saline injections to determine if the pituitary or the adrenal glands, respectively, were rendered more or less sensitive by handling. There was no difference in the responsiveness of H and NH kestrels to either hormone challenge. It is clear from these data that handling had an affect on fledgling phenotypic development, although whether the effects are permanent or ephemeral is unknown. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. 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....... The half-life, T, for human Gc globulin was 12 hr in rats, 16 hr in horses and 30 hr in dogs. The safety profile of plasma-derived Gc globulin is concluded to be consistent to that required for use in man....

  20. Altered lipid partitioning and glucocorticoid availability in CBG-deficient male mice with diet-induced obesity.

    Science.gov (United States)

    Gulfo, José; Ledda, Angelo; Serra, Elisabet; Cabot, Cristina; Esteve, Montserrat; Grasa, Mar

    2016-08-01

    To evaluate how deficiency in corticosteroid-binding globulin (CBG), the specific carrier of glucocorticoids, affects glucocorticoid availability and adipose tissue in obesity. C57BL/6 (WT) and CBG-deficient (KO) male mice were fed during 12 weeks with standard or hyperlipidic diet (HL). Glucocorticoid availability and metabolic parameters were assessed. Body weight and food intake were increased in KO compared with WT mice fed a standard diet and were similar when fed a HL diet. Expression of CBG was found in white adipose tissue by immunochemistry, real-time PCR, and Western blot. In obesity, the subcutaneous depot developed less in KO mice compared with WT, which was associated with a minor adipocyte area and peroxisome proliferator-activated receptor-γ expression. Conversely, the epididymal depot displayed higher weight and adipocyte area in KO than in WT mice. CBG deficiency caused a fall of hepatic 11β-hydroxysteroid dehydrogenase type 2 expression and an increase in epidymal adipose tissue, particularly in HL mice. Deficiency in CBG drives lipid partitioning from subcutaneous to visceral adipose depot under a context of lipid excess and differentially modulates 11β-hydroxysteroid dehydrogenase type 2 expression. © 2016 The Obesity Society.

  1. TeBG- and CBG-bound steroid hormones in rabbits are available for influx into uterus in vivo

    International Nuclear Information System (INIS)

    Chaudhuri, G.; Steingold, K.A.; Pardridge, W.M.; Judd, H.L.

    1988-01-01

    The metabolic clearance rate (MCR) of gonadal or adrenal steroid hormones in rabbits often does not bear the expected inverse relationship with hormone binding to testosterone-binding globulin (TeBG) or corticosteroid-binding globulin (CBG). This suggests TeBG or CBG may not impede steroid hormone delivery to tissues. The effects of rabbit plasma proteins on the influxes of 3 H-labeled steroids from the circulation into the rabbit uterus were measured in vivo using a tissue sampling single-injection technique. In the absence of plasma proteins, estradiol (E 2 ) and testosterone (T) were freely diffusible through the uterine microvasculature (i.e., extraction >80%). The extractions of dihydrostestosterone (DHT) and corticosterone (B) ranged from 60 to 72%, while that of cortisol (F) was reduced at 40%. Rabbit serum exerted no inhibition of the influxes of the steroids tested. The influxes of T and B greatly exceeded the rates that would be expected if only the free and albumin-bound fractions estimated in vitro were diffusible in vivo. However, the extraction of [ 3 H]corticosteroid-binding globulin or bovine [ 3 H]albumin were low, consistent with little, if any, extravascular uptake of the plasma proteins. The results indicate both albumin-bound and globulin-bound steroid hormone are available for transport into the uterus in the rabbit in vivo without significant exodus of the plasma protein, per se

  2. binding globulin gene of Bubalus bubalis bulls in Egypt

    Indian Academy of Sciences (India)

    Lillian

    globulins characterization and gonadal gene expression during sex differentiation in the rainbow trout,. Oncorhynchus mykiss. Mol. Reprod. Dev. 81, 757-765. Miguel-Queralt S., Knowlton M., Avvacumov G. V., Al-Nouno R., Kelly G. M. and Hammond G. L. 2004. Molecular and functional characterization of sex hormone ...

  3. 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 ....... The half-life, T, for human Gc globulin was 12 hr in rats, 16 hr in horses and 30 hr in dogs. The safety profile of plasma-derived Gc globulin is concluded to be consistent to that required for use in man....... potentially be life-saving. This article presents pre-clinical toxicology experiments conducted on purified plasma-derived human Gc globulin. The Gc globulin formulation was shown to be stable for at least 4 years with full retention of actin-binding capacity. In vitro studies did not reveal activation...... of the kallikrein system or the complement system and cellular studies showed no toxic effects on a variety of human cell lines. In vivo studies showed no acute toxic effects in mice, rats or guinea pigs upon intravenous infusion. A 14-day local tolerance study in rabbits showed no adverse effects, and 14-day...

  4. 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.

  5. Application of radioimmunoassay for thyroxine-binding globulin to the determination of the free thyroxine concentration

    International Nuclear Information System (INIS)

    Lecureuil, Michel; Crouzat-Reynes, Gerard; Besnard, J.-C.; Choffel, Christian

    1978-01-01

    A relationship is proposed for calculating the concentration of free serum thyroxine using the measured values of thyroxine and thyroxine-binding globulin total concentrations. This calculation has been performed on a population of 335 patients. A good discrimination of the different thyroid diseases has been obtained [fr

  6. 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...

  7. 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...

  8. 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)

  9. 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

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

    Science.gov (United States)

    ... problems, it can be mistaken for more serious thyroid disorders (such as hypothyroidism). Therefore, it is important to ... TBG Level Health Topic: Newborn Screening Health Topic: Thyroid Diseases Educational Resources (1 link) MalaCards: inherited thyroxine-binding ...

  11. 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

  12. Interactions of thyroxine with thyroxine-binding globulin of low binding capacity

    Energy Technology Data Exchange (ETDEWEB)

    Cuaron, A.

    1987-09-01

    The physico-chemical interactions between thyroxine (T/sub 4/) and thyroxine-binding globulin (TBG) of low binding capacity were investigated by radioimmunoassay, equilibrium dialysis, and reverse flow electrophoresis. Knowledge of total and free T/sub 4/ (FT/sub 4/) concentrations in serum, and of the total binding capacity of the protein carrier (TTBG), allowed the determination of the association constant ruling these interactions (K/sub tbg/). Correlation between T/sub 4/ and FT/sub 4/ varies with TTBG, shifting the normal range for T/sub 4/. The level of FT/sub 4/ in serum is a function of the fractional saturation of TBG by endogenous hormones, which depends on T/sub 4/ and TTBG. Data on T/sub 4/, TTBG, and K/sub tbg/ were integrated into the general equation of the law of mass action and the results showed a very significant linear correlation with the values of FT/sub 4/ measured by equilibrium dialysis. It is concluded that the misleading results of serum T/sub 4/ measurements and of the free T/sub 4/ index, obtained in euthyroid individuals with low TTBG, cannot be ascribed to a reduction of the intrinsic sensitivity of the assay due to oversaturation of TBG by endogenous T/sub 4/, as previously postulated by others, but to a shift of their normal ranges produced by abnormal variations of TTBG. These results stress the need for data regarding TTBG for the proper interpretation of T/sub 4/, and for the calculation of the fractional saturation of TBG and the FT/sub 4/ concentration in serum. The authors have solved this problem by using an empirical equation relating TTBG to T/sub 4/ and triiodothyronine (T/sub 3/) uptake, which was previously derived by other workers.

  13. Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells

    OpenAIRE

    Li, Huika; Pham, Thy; McWhinney, Brett C.; Ungerer, Jacobus P.; Pretorius, Carel J.; Richard, Derek J.; Mortimer, Robin H.; d'Emden, Michael C.; Richard, Kerry

    2016-01-01

    Sex Hormone Binding Globulin (SHBG) is the major serum carrier of sex hormones. However, growing evidence suggests that SHBG is internalised and plays a role in regulating intracellular hormone action. This study was to determine whether SHBG plays a role in testosterone uptake, metabolism, and action in the androgen sensitive LNCaP prostate cancer cell line. Internalisation of SHBG and testosterone, the effects of SHBG on testosterone uptake, metabolism, regulation of androgen responsive gen...

  14. [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.

  15. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-04-01

    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 (/sup 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 (/sup 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.

  18. 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 of epidemiologi...

  19. Globulin Test

    Science.gov (United States)

    ... you have liver or kidney disease . Serum protein electrophoresis. This blood test measures gamma globulins and other ... myeloma. Other names for globulin tests: Serum globulin electrophoresis, total protein What is it used for? Globulin ...

  20. Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers.

    Science.gov (United States)

    Sheikh, Ishfaq A; Turki, Rola F; Abuzenadah, Adel M; Damanhouri, Ghazi A; Beg, Mohd A

    2016-01-01

    Phthalates are a class of high volume production chemicals used as plasticizers for household and industrial use. Several members of this chemical family have endocrine disrupting activity. Owing to ubiquitous environmental distribution and exposure of human population at all stages of life, phthalate contamination is a continuous global public health problem. Clinical and experimental studies have indicated that several phthalates are associated with adverse effects on development and function of human and animal systems especially the reproductive system and exposures during pregnancy and early childhood are by far of utmost concern. Sex hormone-binding globulin (SHBG) is a plasma carrier protein that binds androgens and estrogens and represents a potential target for phthalate endocrine disruptor function in the body. In the present study, the binding mechanism of the nine phthalates i.e. DMP, DBP, DIBP, BBP, DNHP, DEHP, DNOP, DINP, DIDP with human SHBG was delineated by molecular docking simulation. Docking complexes of the nine phthalates displayed interactions with 15-31 amino acid residues of SHBG and a commonality of 55-95% interacting residues between natural ligand of SHBG, dihydrotestosterone, and the nine phthalate compounds was observed. The binding affinity values were more negative for long chain phthalates DEHP, DNOP, DINP, and DIDP compared to short chain phthalates such as DMP and DBP. The Dock score and Glide score values were also higher for long chain phthalates compared to short chain phthalates. Hence, overlapping of interacting amino acid residues between phthalate compounds and natural ligand, dihydrotestosterone, suggested potential disrupting activity of phthalates in the endocrine homeostasis function of SHBG, with long chain phthalates expected to be more potent than the short chain phthalates.

  1. 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)

  2. Relationship between insulin and sex hormone-binding globulin levels during weight loss in obese women.

    Science.gov (United States)

    Akin, Fulya; Bastemir, Mehmet; Kaptanoglu, Bunyamin

    2007-01-01

    The aim of this study was to assess the impact of insulin sensitivity on the relationship between sex hormone-binding globulin (SHBG) and insulin levels during active weight loss in euthyroid obese women. The study population comprised 80 premenopausal overweight and obese (BMI > or =27) women (mean age 41.44 +/- 10.03 years). Seventy patients were considered eligible for the study. Hypocaloric diets were given to all patients. Of 70 subjects who were initially willing to participate in the study, only 64 continued through to the last stage of the study. Anthropometric parameters, metabolic markers and sex hormone status were measured at baseline and on completion of the 12-week study period. Following the diet, significant decreases in insulin, homeostasis model assessment (HOMA) for insulin resistance and fasting glucose were noted. However, HOMA insulin secretion values did not change significantly. Interestingly, there was no significant correlation between SHBG and insulin levels at baseline. After weight loss, SHBG concentrations were significantly and negatively correlated with insulin levels. Therefore, it was concluded that, in severe insulin resistance, insulin does not inhibit the SHBG level. These findings could be important, but the authors have not found a similar relationship in the literature. The findings of this study provide some clues to the relationship between insulin and SHBG in insulin-resistant obese subjects. Insulin sensitivity or loss of fat tissue or leptin seem to be involved in the relationship between SHBG and insulin. (c) 2008 S. Karger AG, Basel

  3. 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.

  4. 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.

  5. 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....

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. 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.

  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. 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

  12. 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

    In 73 euthyroid male patients with histologically verified alcoholic cirrhosis, thyroid hormones, thyroxine-binding globulin (TBG) and testosterone concentrations (total, non-protein- and non-SHBG-bound) were studied in relation to each other and to the degree of liver dysfunction. Serum...... 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....... It is proposed that the association between T3 and TSH on one hand and testosterone concentrations on the other reflects a covariation of these variables with liver function. The TBG level was normal in most patients and was not correlated to testosterone concentrations....

  13. Binding of Ochratoxin A to a Urinary Globulin: A New Concept to Account for Gender Difference in Rat Nephrocarcinogenic Responses

    Directory of Open Access Journals (Sweden)

    Judit Nagy

    2008-05-01

    Full Text Available SDS-gradient mini-gel electrophoresis and immunoblotting of urine of rats given ochratoxin A (OTA, showed OTA binding to an α2u-globulin. Perceived potential internalised delivery of OTA to proximal tubule epithelia by the carrier, specific only to adult male rats and augmenting other uptake mechanisms, suggests that some experimental nephrotoxicological data may not be appropriate for human risk assessment. Reexamination of female rat renal tumour histopathology of the NTP high dose OTA study showed all carcinomas were solitary, unilateral, microscopic and clinically insignificant at the 2-year end-stage. The novel concept, when consolidated further from our archived material, may moderate current perceptions of the human risk of traces of dietary OTA.

  14. Serum testosterone, sex hormone-binding globulin and total calcium levels predict the calcaneal speed of sound in men.

    Science.gov (United States)

    Chin, Kok-Yong; Soelaiman, Ima-Nirwana; Mohamed, Isa Naina; Ngah, Wan Zurinah Wan

    2012-08-01

    Variations in sex hormones and the calcium balance can influence bone health in men. The present study aimed to examine the relationship between the calcaneal speed of sound and biochemical determinants of bone mass, such as sex hormones, parathyroid hormones and serum calcium. Data from 549 subjects from the Malaysian Aging Male Study, which included Malay and Chinese men aged 20 years and older residing in the Klang Valley, were used for analysis. The subjects' calcaneal speed of sound was measured, and their blood was collected for biochemical analysis. Two sets of multiple regression models were generated for the total/bioavailable testosterone and estradiol to avoid multicollinearity. The multiple regression results revealed that bioavailable testosterone and serum total calcium were significant predictors of the calcaneal speed of sound in the adjusted model. After adjustment for ethnicity and body mass index, only bioavailable testosterone remained significant; the total serum calcium was marginally insignificant. In a separate model, the total testosterone and sex hormone-binding globulin were significant predictors, whereas the total serum calcium was marginally insignificant. After adjustment for ethnicity and body mass index (BMI), the significance persisted for total testosterone and SHBG. After further adjustment for age, none of the serum biochemical determinants was a significant predictor of the calcaneal speed of sound. There is a significant age-dependent relationship between the calcaneal speed of sound and total testosterone, bioavailable testosterone and sex hormone-binding globulin in Chinese and Malay men in Malaysia. The relationship between total serum calcium and calcaneal speed of sound is ethnicity-dependent.

  15. 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.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

    Brand, J.S.; Rovers, M.M.; Yeap, B.B.; Schneider, H.J.; Tuomainen, T.P.; Haring, R.; Corona, G.; Onat, A.; Maggio, M.; Bouchard, C.; Tong, P.C.; Chen, R.Y.; Akishita, M.; Gietema, J.A.; Gannage-Yared, M.H.; Unden, A.L.; Hautanen, A.; Goncharov, N.P.; Kumanov, P.; Chubb, S.A.; Almeida, O.P.; Wittchen, H.U.; Klotsche, J.; Wallaschofski, H.; Volzke, H.; Kauhanen, J.; Salonen, J.T.; Ferrucci, L.; Schouw, Y.T. van der

    2014-01-01

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

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

    NARCIS (Netherlands)

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

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

  19. 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)

  20. Community responses to CBG experiences in BC

    Energy Technology Data Exchange (ETDEWEB)

    Coward, M. [British Columbia Ministry of Energy and Mines, Victoria, BC (Canada)

    2003-07-01

    Coalbed gas (CBG) is expected to play a prominent role in British Columbia in the future, and the British Columbia Ministry of Energy and Mines is looking to generate $20 billion of cumulative investment in the oil and gas sector by 2008 through the identification, stimulation, and facilitation of development opportunities for under-developed and unconventional resources. A brief overview of CBG potential in the province was provided. The common concerns that have been expressed by diverse communities throughout the province include jobs, economic growth opportunities, and environmental impact. These communities are composed of landowners, business people, other resource owners, municipal and regional governments, general public, environmental interest groups, and First Nations. The government's approach to communities involves consultation with First Nations, which are key to resource development and have very diverse interests and approaches. The approach includes real communication, real information, and real issues. Good community relations should lead to reduced uncertainty for development, better resource development through the identification of issues, and increased confidence in government, regulators and industry by communities. The roles of the British Columbia Ministry of Energy and Mines and the Oil and Gas Commission were described, as they relate to community relations in the province. Lessons learned on topics such as water, land disturbance, and baseline studies while working with First Nations were reviewed, . figs.

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

    Science.gov (United States)

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

    2016-03-01

    The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N=1463, including 1054 with follow-up data 4.6years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade≥2, N=140, 9.6%) and new or worsening vertebral fracture (change in SQ grade≥1, N=55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Perry, John R.B.; Weedon, Michael N.; Langenberg, Claudia; Jackson, Anne U.; Lyssenko, Valeriya; Sparsø, Thomas; Thorleifsson, Gudmar; Grallert, Harald; Ferrucci, Luigi; Maggio, Marcello; Paolisso, Giuseppe; Walker, Mark; Palmer, Colin N.A.; Payne, Felicity; Young, Elizabeth; Herder, Christian; Narisu, Narisu; Morken, Mario A.; Bonnycastle, Lori L.; Owen, Katharine R.; Shields, Beverley; Knight, Beatrice; Bennett, Amanda; Groves, Christopher J.; Ruokonen, Aimo; Jarvelin, Marjo Riitta; Pearson, Ewan; Pascoe, Laura; Ferrannini, Ele; Bornstein, Stefan R.; Stringham, Heather M.; Scott, Laura J.; Kuusisto, Johanna; Nilsson, Peter; Neptin, Malin; Gjesing, Anette P.; Pisinger, Charlotta; Lauritzen, Torsten; Sandbaek, Annelli; Sampson, Mike; Zeggini, MAGIC, Ele; Lindgren, Cecilia M.; Steinthorsdottir, Valgerdur; Thorsteinsdottir, Unnur; Hansen, Torben; Schwarz, Peter; Illig, Thomas; Laakso, Markku; Stefansson, Kari; Morris, Andrew D.; Groop, Leif; Pedersen, Oluf; Boehnke, Michael; Barroso, Inês; Wareham, Nicholas J.; Hattersley, Andrew T.; McCarthy, Mark I.; Frayling, Timothy M.

    2010-01-01

    Epidemiological studies consistently show that circulating sex hormone binding globulin (SHBG) levels are lower in type 2 diabetes patients than non-diabetic individuals, but the causal nature of this association is controversial. Genetic studies can help dissect causal directions of epidemiological associations because genotypes are much less likely to be confounded, biased or influenced by disease processes. Using this Mendelian randomization principle, we selected a common single nucleotide polymorphism (SNP) near the SHBG gene, rs1799941, that is strongly associated with SHBG levels. We 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 × 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 standard deviations higher per copy of the A allele) and the SHBG levels versus type 2 diabetes association (SHBG levels are 0.23 standard deviations lower in type 2 diabetic patients compared to controls). Results were very similar in men and women. There was no evidence that this variant is associated with diabetes-related intermediate traits, including several measures of insulin secretion and resistance. Our results, together with those from another recent genetic study, strengthen evidence that SHBG and sex hormones are involved in the aetiology of type 2 diabetes. PMID:19933169

  3. 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.

  4. Association of bioavailable, free, and total testosterone with insulin resistance: influence of sex hormone-binding globulin and body fat.

    Science.gov (United States)

    Tsai, Elaine C; Matsumoto, Alvin M; Fujimoto, Wilfred Y; Boyko, Edward J

    2004-04-01

    Previous reports of an association between low testosterone levels and diabetes risk were often confounded by covariation of sex hormone-binding globulin (SHBG) and testosterone measurements. Measurements of bioavailable and free testosterone, more reliable indexes of biologically active testosterone, were examined for their associations with markers of insulin resistance and body fat measures in 221 middle-aged nondiabetic men. Bioavailable and free testosterone were calculated from the concentrations of total testosterone, SHBG, and albumin, and they were not significantly correlated with SHBG (r = 0.07-0.1). In contrast, total testosterone correlated significantly with SHBG (r = 0.63). We evaluated the relationship between these measures of circulating testosterone and markers for insulin resistance (i.e., fasting insulin, C-peptide, and homeostasis model assessment for insulin resistance [HOMA-IR]) as well as total body fat (assessed by dual-energy X-ray absorptiometry [DEXA]) and abdominal fat distribution (assessed by single-slice computed tomography [CT]). Bioavailable, free, and total testosterone and SHBG all correlated significantly with fasting insulin (age-adjusted r = -0.15 [P = 0.03], -0.14 [P = 0.03], -0.32 [P fat measures (r = -0.17 [P = 0.008] to -0.44 [P testosterone were significantly associated with fasting glucose (r = -0.20 [P = 0.003] to -0.21 [P = 0.002]). In multivariate analysis, bioavailable or free testosterone was significantly and inversely associated with insulin, C-peptide, and HOMA-IR, but this was not independent of total body or abdominal fat. SHBG was a significant determinant of insulin, C-peptide, and HOMA-IR, independent of body fat. The associations between total testosterone and insulin resistance were confounded by SHBG. The inverse association between testosterone and insulin resistance, independent of SHBG, was mediated through body fat.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    de Torres Inés

    2009-06-01

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

  7. First Trimester Maternal Glycated Hemoglobin and Sex Hormone-Binding Globulin Do Not Predict Third Trimester Glucose Intolerance of Pregnancy.

    Science.gov (United States)

    Berggren, Erica K; Boggess, Kim A; Mathew, Leny; Culhane, Jennifer

    2017-04-01

    Early pregnancy prediction of third trimester glucose intolerance may identify a population of women whose trajectory toward gestational diabetes mellitus (GDM) is modifiable. We assessed whether first trimester glycated hemoglobin (HbA1c) and sex hormone-binding globulin (SHBG), markers of insulin resistance, predicted third trimester glucose intolerance. Nondiabetic women with singleton pregnancies enrolled in a prospective observational study, 11 0/7 to 14 6/7 weeks. At enrollment, maternal characteristics, medical history, and blood samples were collected for HbA1c and SHBG. Two-step GDM screening was performed, 22 0/7 to 33 6/7 weeks. A 50 g oral glucose tolerance test ≥130 mg/dL defined screen positive, or glucose intolerance. Carpenter-Coustan criteria diagnosed GDM. Means HbA1c and SHBG were compared between glucose-intolerant versus normoglycemic women, and GDM versus no GDM women. We report unadjusted and adjusted odds ratios (OR; 95% confidence interval [CI]) of regression analyses. Adjusted models include race, enrollment body mass index, and history of GDM. Among 250 women, 29% were glucose intolerant and 6% had GDM. Among glucose-intolerant women, HbA1c was higher (5.3 ± 0.3 vs. 5.1 ± 0.3, P = .01) and associated with glucose intolerance in unadjusted, but not adjusted, models (OR: 2.9, 95% CI: 1.2-7.1; adjusted odds ratio [aOR]: 2.0, 95% CI: 0.7-5.4). Among GDM women, HbA1c was higher (5.4 ± 0.4 vs 5.2 ± 0.3, P = .002) and SHBG was lower (228 ± 72 vs 288 ± 93 mmol/L, P = .02). The HbA1c predicted GDM in unadjusted (OR: 13.2, 95% CI: 2.6-68.0) but not adjusted (aOR: 6.7, 95% CI: 0.8-55.2) models. Although metabolic alterations may well precede third trimester glucose intolerance, neither HbA1c of SHBG remained an independent predictor of glucose intolerance or GDM in adjusted models.

  8. Serum globulin electrophoresis

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003544.htm Serum globulin electrophoresis To use the sharing features on this page, please enable JavaScript. The serum globulin electrophoresis test measures the levels of proteins called globulins ...

  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. 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

  12. Purification of equine Gc-globulin

    DEFF Research Database (Denmark)

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

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

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

    Directory of Open Access Journals (Sweden)

    Yeager Meredith

    2007-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ostrowska, Z.; Buntner, B.; Marek, B.; Zwirska-Korczala, K. [Slaska Akademia Medyczna, Katowice (Poland)

    1995-12-31

    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{sub 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{sup 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{sub 2} levels were elevated. (author). 49 refs, 4 figs, 2 tabs.

  15. The associations of endogenous testosterone and sex hormone-binding globulin with glycosylated hemoglobin levels, in community dwelling men. The Tromsø Study.

    Science.gov (United States)

    Svartberg, J; Jenssen, T; Sundsfjord, J; Jorde, R

    2004-02-01

    Low levels of endogenous testosterone have been associated with increased risk of cardiovascular disease and atherosclerosis in men. Long-term hyperglycemia, as measured by glycosylated hemoglobin (HbA1c), is related to cardiovascular mortality, and HbA1c across its normal range is also positively related to coronary heart and cardiovascular disease mortality in men. We therefore undertook an analysis of the cross-sectional associations of total testosterone and SHBG levels with HbA1c levels, in a general population of 1419 men aged 25-84. Total testosterone, sex hormone-binding globulin (SHBG) and HbA1c were measured by immuno-assay. Partial correlation and multiple regression analyses were used to estimate the associations between total testosterone and SHBG with HbA1c. Analyses of variance and covariance were used to compare men with or without diabetes. In age-adjusted partial correlation HbA1c was inversely associated with total testosterone (ptestosterone, SHBG, age, number of cigarettes smoked, BMI and WC were independently associated with HbA1c levels. Men with a history of diabetes had lower levels of total testosterone in age-adjusted analyses (ptestosterone and SHBG were associated with increased HbA1c levels and diabetes independent of concomitant variations in obesity and body fat distribution.

  16. Relationships of plasma estradiol, testosterone, and sex hormone-binding globulin with lipoproteins, apolipoproteins, and high density lipoprotein subfractions in men.

    Science.gov (United States)

    Stefanick, M L; Williams, P T; Krauss, R M; Terry, R B; Vranizan, K M; Wood, P D

    1987-04-01

    Plasma estradiol, testosterone, and sex hormone-binding globulin (SHBG) were studied in relation to plasma lipoproteins, high density lipoprotein (HDL) subfractions, and apolipoproteins in 73 healthy but sedentary middle-aged men. Among potentially confounding variables, a strong positive association was found between estradiol levels and cigarette use, while testosterone and SHBG correlated negatively with percent body fat and alcohol intake. After adjustment for smoking, percent body fat, and alcohol, plasma estradiol levels correlated negatively with total cholesterol and low density lipoprotein cholesterol, and testosterone levels correlated positively with apolipoprotein B, while SHBG levels correlated positively with HDL2 mass and apolipoprotein A-I. SHBG was also strongly associated with the waist to hip girth ratio (WHR). Adjustment for WHR eliminated the significant associations of SHBG with triglycerides, HDL2 mass, and apolipoprotein A-I. SHBG levels and WHR may reflect tissue sensitivity and the impact of exposure to fluctuating levels of sex hormones for a period of days, or longer. These variables may provide more insight into the role of sex hormones in lipoprotein metabolism than do single samples of circulating hormones. It is also suggested that long term effects of sex hormones on adipose tissue distribution may at least partially underlie sex-related differences in lipoprotein metabolism.

  17. A genetic study of sex hormone--binding globulin measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

    Science.gov (United States)

    An, P; Rice, T; Gagnon, J; Hong, Y; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

    2000-08-01

    Familial aggregation and a major gene effect were assessed for baseline serum sex hormone-binding globulin (SHBG) levels and the response (post-training minus baseline) to a 20-week endurance training program in a selected sample of 428 non-obese nonhypertensive individuals from 99 white families who were sedentary at baseline in the HERITAGE Family Study. Baseline SHBG levels were not normally distributed, and were therefore logarithmically transformed prior to genetic analyses. In a sample without postmenopausal mothers, maximal (genetic and familial environmental) heritabilities were 50% averaged across sexes, 73% in men, 50% in women, and 31% in men versus women for the age-body mass index (BMI)-adjusted baseline. The estimate reached 64% when the baseline was further adjusted for the effects of estradiol, fasting insulin, and testosterone levels. For the response to training, no sex difference was found and the heritability reached about 25% to 32%. Segregation analysis was separately performed in the whole sample and in the sample without postmenopausal mothers. In addition to a multifactorial effect for both the baseline and the response to training, a major effect for the baseline appeared to be familial environmental in origin, whereas a major effect for the response to training was Mendelian in nature. The major gene effect for the response to training in the whole sample was undetectable in the sample without postmenopausal mothers, and it is therefore possible that the postmenopausal mothers, characterized by decreased sex hormones with or without estrogen replacement therapy for menopause, produced some confounding effects. In addition, the reduced sample size might also be a plausible candidate explanation. The novel finding in this study is that baseline SHBG levels and the response to training were influenced by a multifactorial effect with sex difference for the baseline. The response to training appeared to be additionally influenced by a single

  18. Association of sex hormones and sex hormone-binding globulin with depressive symptoms in postmenopausal women: the Multiethnic Study of Atherosclerosis.

    Science.gov (United States)

    Colangelo, Laura A; Craft, Lynette L; Ouyang, Pamela; Liu, Kiang; Schreiner, Pamela J; Michos, Erin D; Gapstur, Susan M

    2012-08-01

    Sex hormones are thought to play an important role in the pathophysiology of depressive disorders in women. This study assessed the associations of total testosterone (T), bioavailable T, estradiol, dehydroepiandrosterone, and sex hormone-binding globulin (SHBG) with depressive symptoms stratified on postmenopausal stage to determine whether the associations were strongest for early postmenopausal women. Women (N = 1,824) free of depressive symptoms at baseline (2000-2002) in the Multiethnic Study of Atherosclerosis were categorized into tertiles of years postmenopause: T1, 0 to 10 years; T2, 11 to 20 years; and T3, 21 to 58 years. Multivariable-adjusted relative risks (RRs) and 95% CIs were computed for the incidence of depressive symptoms, as defined by a score of 16 or higher on the Center for Epidemiologic Studies Depression scale at examination 3 (2004-2005). In analysis including all sex hormones, the RR for incident depressive symptoms associated with 1 unit higher log total T was 0.57 (P = 0.13), with log estradiol was 0.78 (P = 0.04), with log SHBG was 1.84 (P = 0.003), and with log dehydroepiandrosterone was 1.45 (P = 0.08) in T1. Without adjustment for SHBG, the RR for log bioavailable T was 0.16 (P = 0.04). However, in T2 and T3, there were no meaningful associations of hormone or SHBG levels with incident depressive symptoms. When stratified by HT use, results were consistent for HT users but attenuated for HT nonusers. In early postmenopausal women, sex hormones were associated with incident depressive symptoms.

  19. The association of obesity with sex hormone-binding globulin is stronger than the association with ageing – implications for the interpretation of total testosterone measurements

    Science.gov (United States)

    Cooper, Lori A.; Page, Stephanie T.; Amory, John K.; Anawalt, Bradley D.; Matsumoto, Alvin M.

    2016-01-01

    Summary Objective Total testosterone concentrations are influenced by sex hormone-binding globulin (SHBG) concentrations, which are decreased by obesity and increased with ageing. Therefore, we sought to understand and compare the associations of ageing and obesity with SHBG. Design We performed a retrospective, cross-sectional analysis of the associations of obesity and age on SHBG and testosterone measurements in men being evaluated for hypogonadism. Patients, Measurements and Analysis A total of 3671 men who underwent laboratory testing for testosterone deficiency from the Veterans Administration Puget Sound Health Care System from 1997 through 2007 was included. Univariate and multivariate linear regression modelling of the associations between age and body mass index (BMI) and SHBG was performed. Results Obesity was associated with a significantly lower SHBG [β = −1·26 (95% CI −1·14, −1·38) nmol/l] per unit increase in BMI. In contrast, ageing was associated with a significantly increased SHBG [β = 0·46 (95% CI 0·39, 0·53) nmol/l per year] (P obesity with lower SHBG was two to three times larger than the association of ageing with increased SHBG in both univariate and multivariate modelling. On average, obese men (BMI >30 kg/m2) had significantly lower SHBG and total testosterone concentrations than nonobese men [(mean ± SD) SHBG: 36 ± 22 vs 50 ± 27 nmol/l and total testosterone: 10·5 ± 5·4 nmol/l vs 14·1 ± 7·4 nmol/l; (P testosterone concentrations did not differ between obese and nonobese men. Conclusions We found that the association between obesity and lowered SHBG is greater than the association of ageing with increased SHBG. These competing effects may impact total testosterone measurements for the diagnosis of low testosterone, particularly in obese men. PMID:25777143

  20. The association of obesity with sex hormone-binding globulin is stronger than the association with ageing--implications for the interpretation of total testosterone measurements.

    Science.gov (United States)

    Cooper, Lori A; Page, Stephanie T; Amory, John K; Anawalt, Bradley D; Matsumoto, Alvin M

    2015-12-01

    Total testosterone concentrations are influenced by sex hormone-binding globulin (SHBG) concentrations, which are decreased by obesity and increased with ageing. Therefore, we sought to understand and compare the associations of ageing and obesity with SHBG. We performed a retrospective, cross-sectional analysis of the associations of obesity and age on SHBG and testosterone measurements in men being evaluated for hypogonadism. A total of 3671 men who underwent laboratory testing for testosterone deficiency from the Veterans Administration Puget Sound Health Care System from 1997 through 2007 was included. Univariate and multivariate linear regression modelling of the associations between age and body mass index (BMI) and SHBG was performed. Obesity was associated with a significantly lower SHBG [β = -1·26 (95% CI -1·14, -1·38) nmol/l] per unit increase in BMI. In contrast, ageing was associated with a significantly increased SHBG [β = 0·46 (95% CI 0·39, 0·53) nmol/l per year] (P obesity with lower SHBG was two to three times larger than the association of ageing with increased SHBG in both univariate and multivariate modelling. On average, obese men (BMI >30 kg/m(2)) had significantly lower SHBG and total testosterone concentrations than nonobese men [(mean ± SD) SHBG: 36 ± 22 vs 50 ± 27 nmol/l and total testosterone: 10·5 ± 5·4 nmol/l vs 14·1 ± 7·4 nmol/l; (P testosterone concentrations did not differ between obese and nonobese men. We found that the association between obesity and lowered SHBG is greater than the association of ageing with increased SHBG. These competing effects may impact total testosterone measurements for the diagnosis of low testosterone, particularly in obese men. © 2015 John Wiley & Sons Ltd.

  1. 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.

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

    DEFF Research Database (Denmark)

    Pihl, Tina Holberg

    Group specific (Gc) globulin also known as vitamin D-binding protein is part of the extracellular actin-scavenging system that removes actin from the circulation. Actin is an intracellular structural protein, which is released to blood in patients with tissue injury and cell death. Circulating ac......-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....

  3. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M

    1994-01-01

    system allowing us to distinguish between the different electrophoretic patterns in small amounts of plasma or serum (10 microliters). Small aliquots of Blue Sepharose were added to diluted sera or plasma samples for removal of albumin and the supernatants were subsequently applied to Western blotting...

  4. 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.

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

    Science.gov (United States)

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

    2014-01-01

    Background Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably. Objectives We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components. Data sources Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE. Study Eligibility Criteria Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men. Methods 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. Results 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. Conclusions 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. PMID:25019163

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    exchange chromatography. The separated isoforms and several commercial preparations of individual isoforms were characterized by mass spectrometry. This revealed that the major isoforms were non-glycosylated. Compared to the Gc-1f isoform the other dominating isoforms represented an Asp/Glu substitution...... (Gc-1s) and a Thr/Lys substitution (Gc-2) in agreement with DNA sequencing studies. The commercial preparations were found to represent mainly one or two isoforms. An O-linked glycan with a mass of 656 Da and terminating with a sialic acid residue was detected on a minor proportion of Gc globulin...

  9. 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.

  10. Desenvolvimento de ensaio imunofluorométrico para a medida da globulina ligadora de tiroxina (thyroxine-binding globulin, TBG e sua aplicação em casos de deficiência desta proteína Development of an immunofluorometric assay for thyroxine-binding globulin (TBG and its application in cases of protein deficiency

    Directory of Open Access Journals (Sweden)

    José Gilberto H. Vieira

    2002-01-01

    Full Text Available A globulina ligadora de tiroxina (thyroxine-binding globulin, TBG é a principal transportadora de hormônios tiroidianos no soro. Variações na concentração sérica de TBG determinam variações proporcionais nas concentrações séricas totais de T4 e T3, sem implicar alterações de função, desde que a fração livre permaneça normal. Várias condições clínicas comuns levam a alterações significativas nos níveis de TBG, sendo as variações mais importantes devidas a defeitos genéticos. Como a TBG é codificada por gene localizado no cromossomo X, os defeitos se manifestam mais facilmente no sexo masculino. Descrevemos o desenvolvimento de ensaio imunofluorométrico para a medida de TBG com base em anticorpos monoclonais, sendo um desenvolvido em nosso laboratório e outro comercial. O método apresenta sensibilidade de 0,8mg/l e coeficientes de variação intra e interensaio inferiores a 10%. O estudo comparativo com método comercial mostrou alta correlação (r = 0,93; n = 48, sendo os valores normais obtidos de 10mg/l a 29mg/l. Estudamos também 20 indivíduos portadores de deficiência congênita de TBG, 19 homens e uma mulher, que apresentavam valores normais de TSH e baixos de T4 total; em todos eles os níveis de TBG foram indetectáveis. Já os níveis de T4 livre medidos por método indireto em 16 desses indivíduos mostraram-se elevados em todos, ao passo que, quando medidos por método direto pós-diálise nos quatro restantes, mostraram-se normais. Nossos resultados reforçam a necessidade prática da disponibilidade de ensaio para a medida de TBG para esclarecimento e definição diagnóstica de alguns casos especiais, principalmente quando o ensaio de T4 livre direto, pós-diálise, não é disponível.Thyroxine-binding globulin (TBG is the main responsible for serum thyroid hormone transport. Serum variations in TBG concentrations determine proportional variations in serum total T4 and T3 concentrations, without

  11. Computational insights into the molecular interactions of environmental xenoestrogens 4-tert-octylphenol, 4-nonylphenol, bisphenol A (BPA), and BPA metabolite, 4-methyl-2, 4-bis (4-hydroxyphenyl) pent-1-ene (MBP) with human sex hormone-binding globulin.

    Science.gov (United States)

    Sheikh, Ishfaq A; Tayubi, Iftikhar A; Ahmad, Ejaz; Ganaie, Majid A; Bajouh, Osama S; AlBasri, Samera F; Abdulkarim, Ibtihal M J; Beg, Mohd A

    2017-01-01

    Environmental contamination has been one of the major drawbacks of the industrial revolution. Several man-made chemicals are constantly released into the environment during the manufacturing process and by leaching from the industrial products. As a result, human and animal populations are exposed to these synthetic chemicals on a regular basis. Many of these chemicals have adverse effects on the physiological functions, particularly on the hormone systems in human and animals and are called endocrine disrupting chemicals (EDCs). Bisphenol A (BPA), 4-tert-octylphenol (OP), and 4-nonylphenol (NP) are three high volume production EDCs that are widely used for industrial purposes and are present ubiquitously in the environment. Bisphenol A is metabolized in the human body to a more potent compound (MBP: 4-Methyl-2, 4-bis (4-hydroxyphenyl) pent-1-ene). Epidemiological and experimental studies have shown the three EDCs to be associated with adverse effects on reproductive system in human and animals. Sex hormone-binding globulin (SHBG) is a circulatory protein that binds sex steroids and is a potential target for endocrine disruptors in the human body. The current study was done in order to understand the binding mechanism of OP, BPA, NP, and MBP with human SHBG using in silico approaches. All four compounds showed high binding affinity with SHBG, however, the binding affinity values were higher (more negative) for MBP and NP than for OP and BPA. The four ligands interacted with 19-23 residues of SHBG and a consistent overlapping of the interacting residues for the four ligands with the residues for the natural ligand, dihydrotestosterone (DHT; 82-91% commonality) was shown. The overlapping SHBG interacting residues among DHT and the four endocrine disruptors suggested that these compounds have potential for interference and disruption in the steroid binding function. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. 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.)

  13. 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

  14. 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.

  15. Radioimmunoassay of ''free thyroxin'' in dried blood spots on filter paper - preliminary observations on the effective differentiation of subjects with congenital hypothyroidism from those with subnormal thyroxin-binding globulin and normal subjects

    International Nuclear Information System (INIS)

    Mizuta, H.; Miyai, K.; Ichihara, K.; Amino, N.; Harada, T.; Nose, O.; Tanizawa, O.

    1982-01-01

    In this sensitive, simple method for measuring ''free thyroxin'' (FT 4 ) in eluates of dried blood spots on filter paper by use of a radioimmunoassay kit (Amerlex Free T 4 RIA), the measurable range of FT 4 is 1.8 to 57 ng/L (equivalent to the concentration in serum), or 7 to 237 fg/tube. The mean coefficients of variation for within assay-within spots, within assay-between spots, and between assays were 5.3%, 5.0%, and 6.2%, respectively. FT 4 in blood spotted on filter paper is stable for at least a month when dried and kept at either -20 0 C, 4 0 C, room temperature (about 25 0 C), or 37 0 C. The results for FT 4 in dried blood spots correlated closely with the free-T 4 concentration in serum (r = 0.99). The method can be used to differentiate cases of primary and secondary hypothyroidism from normal subjects and those with subnormal thyroxin-binding globulin. This method may be useful in screening for congenital hypothyroidism, because sample-retesting is not necessary

  16. Vicilins (7S storage globulins of cowpea (Vigna unguiculata seeds bind to chitinous structures of the midgut of Callosobruchus maculatus (Coleoptera: Bruchidae larvae

    Directory of Open Access Journals (Sweden)

    Sales M.P.

    2001-01-01

    Full Text Available The presence of chitin in midgut structures of Callosobruchus maculatus larvae was shown by chemical and immunocytochemical methods. Detection by Western blotting of cowpea (Vigna unguiculata seed vicilins (7S storage proteins bound to these structures suggested that C. maculatus-susceptible vicilins presented less staining when compared to C. maculatus-resistant vicilins. Storage proteins present in the microvilli in the larval midgut of the bruchid were recognized by immunolabeling of vicilins in the appropriate sections with immunogold conjugates. These labeling sites coincided with the sites labeled by an anti-chitin antibody. These results, taken together with those previously published showing that the lower rates of hydrolysis of variant vicilins from C. maculatus-resistant seeds by the insect's midgut proteinases and those showing that vicilins bind to chitin matrices, may explain the detrimental effects of variant vicilins on the development of C. maculatus larvae.

  17. 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.

  18. 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.

  19. 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...

  20. Synthesis of the constrained glutamate analogues (2S,1 ' R,2 ' R)- and (2S,1 ' S,2 ' S)-2- (2 'carboxycyclobutyl)glycines L-CBG-II and L-CBG-I by enzymatic transamination

    OpenAIRE

    Gu , Xin; Xian , Mo; Roy-Faure , Sophie; Bolte , Jean; Aitken , David J; Gefflaut , Thierry

    2006-01-01

    Optically pure trans-cyclobutane analogues of glutamic acid are prepared by highly selective enzymatic transamination of a single racemic trans-cyclobutane α-ketoglutaric acid derivative 5, which is synthesized in five steps from maleic anhydride. (2S,1′R,2′R)- and (2S,1′S,2′S)-2-(2′-carboxycyclobutyl)glycines L-CBG-II and L-CBG-I are obtained using aspartate aminotransferase (AAT) and branched chain aminotransferase (BCAT), respectively.

  1. 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

  2. Insights into the 1.59-Mbp largest plasmid of Azospirillum brasilense CBG497.

    Science.gov (United States)

    Acosta-Cruz, Erika; Wisniewski-Dyé, Florence; Rouy, Zoé; Barbe, Valérie; Valdés, María; Mavingui, Patrick

    2012-09-01

    The plant growth-promoting proteobacterium Azospirillum brasilense enhances growth of many economically important crops, such as wheat, maize, and rice. The sequencing and annotation of the 1.59-Mbp replicon of A. brasilense CBG497, a strain isolated from a maize rhizosphere grown on an alkaline soil in the northeast of Mexico, revealed a GC content of 68.7 % and the presence of 1,430 potential protein-encoding genes, 1,147 of them classified into clusters of orthologous groups categories, and 16 tRNA genes representing 11 tRNA species. The presence of sixty-two genes representatives of the minimal gene set and chromid core genes suggests its importance in bacterial survival. The phaAB → G operon, reported as involved in the bacterial adaptation to alkaline pH in the presence of K(+), was also found on this replicon and detected in several Azospirillum strains. Phylogenetic analysis suggests that it was laterally acquired. We were not able to show its inference on the adaptation to basic pH, giving a hint about the presence of an alternative system for adaptation to alkaline pH.

  3. 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

  4. 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......) were determined to evaluate their predictive values in relation to survival/nonsurvival. Gc-globulin levels were significantly reduced in 47 nonsurvivors, compared with 30 survivors (96 +/- 71 mg/L vs. 169 +/- 101 mg/L, P ... of patients with non-acetaminophen-induced FHF, whereas a higher value predicted survival in 60 percent. In patients with acetaminophen-induced FHF, nonsurvival was correctly predicted in 100 percent of patients and survival in 53 percent. In comparison, the King's College Hospital (KCH) criteria correctly...

  5. 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)

  6. 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.

  7. Cannabinoid receptor 1 binding activity and quantitative analysis of Cannabis sativa L. smoke and vapor.

    Science.gov (United States)

    Fischedick, Justin; Van Der Kooy, Frank; Verpoorte, Robert

    2010-02-01

    Cannabis sativa L. (cannabis) extracts, vapor produced by the Volcano vaporizer and smoke made from burning cannabis joints were analyzed by GC-flame ionization detecter (FID), GC-MS and HPLC. Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol. Cannabinoids plus other components such as terpenoids and pyrolytic by-products were identified and quantified in all samples. Cannabis vapor and smoke was tested for cannabinoid receptor 1 (CB1) binding activity and compared to pure Delta(9)-tetrahydrocannabinol (Delta(9)-THC). The top five major compounds in Bedrocan extracts were Delta(9)-THC, cannabigerol (CBG), terpinolene, myrcene, and cis-ocimene in Bedrobinol Delta(9)-THC, myrcene, CBG, cannabichromene (CBC), and camphene in Bediol cannabidiol (CBD), Delta(9)-THC, myrcene, CBC, and CBG. The major components in Bedrocan vapor (>1.0 mg/g) were Delta(9)-THC, terpinolene, myrcene, CBG, cis-ocimene and CBD in Bedrobinol Delta(9)-THC, myrcene and CBD in Bediol CBD, Delta(9)-THC, myrcene, CBC and terpinolene. The major components in Bedrocan smoke (>1.0 mg/g) were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene. There was no statistically significant difference between CB1 binding of pure Delta(9)-THC compared to cannabis smoke and vapor at an equivalent concentration of Delta(9)-THC.

  8. Concentrations, metabolic clearance rates, production rates and plasma binding of cortisol in Antarctic phocid seals.

    Science.gov (United States)

    Liggins, G C; France, J T; Schneider, R C; Knox, B S; Zapol, W M

    1993-10-01

    We have reported previously that plasma of the Weddell seal, a member of the phocid family, contains a very high concentration of cortisol. The present study was undertaken to determine whether high cortisol levels were common to seals in the Antarctic environment, or to other phocidae, and to determine the mechanism of the hypercortisolaemia. High levels of cortisol (0.82-2.38 mumol/l) were found in 4 phocidae (Weddell, crabeater, leopard and Southern elephant seals), whereas levels in a member of the otariid family (Antarctic fur seal) were similar to human values. Metabolic clearance rates (MCR) and production rates (PR) of cortisol were determined in the field in Weddell (N = 1), crabeater (N = 3) and leopard (N = 3) seals following bolus injections of [3H] cortisol. The MCR and PR did not differ between the three phocids, but whereas the MCR of 410-590 1/day was twice that of human values, the PR of 460-1180 mumol.m-2 x d-1 was up to 40-fold greater. The binding capacity of corticosteroid-binding globulin (CBG) was equal to or greater than the plasma concentrations of cortisol, resulting in relatively low concentrations of free cortisol. We conclude that hypercortisolaemia is maintained in phocid seals mainly by a high production rate--the highest (corrected for surface area) reported in any species. The relatively low cortisol levels in otariid seals studied in the same environment suggest that the high PR in phocidae is unrelated to the harsh climatic conditions, but may be part of their adaptation for diving to extreme depths.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. 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.

  10. 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.

  11. [Effects of copper and zinc cations bound by gamma-globulin fraction in Staphylococcus aureus culture].

    Science.gov (United States)

    Cheknev, S B; Vostrova, E I; Piskovskaia, L S; Vostrov, A V

    2014-01-01

    AIM. Evaluation of Staphylococcus aureus culture growth dynamics in the presence of gamma-globulin: metal-complexes formed with copper and zinc cations as well as cations of metals used in isolation during the first 24 hours of exposition. . Samples of human gamma-globulin metal-complexes with copper or zinc cations at a final concentration of 0.5 microg/ml were introduced into S. aureus bacteria suspensions containing approximately 10(3) CFU/ml. Suspension at the volume of 5.0 ml was incubated at 37 degrees C for 24 hours with sampling and CFU calculation in the culture at various exposure periods. An accepted micromethod for determination of viability of bacteria was used. The protein transformed by copper cation binding realizes bacteriostatic activity in the logarithmic growth phase of S. aureus culture from 3.0 to 6.0 hours of incubation. Free copper cations inhibit bacterial reproduction at a higher degree than the metal-complex. The protein transformed by zinc cation binding realizes bacteriostatic activity at 1.5 hours of S. aureus incubation. Free zinc cations do not have bacteriostatic effect against S. aureus. Proteins of the gamma-globulin fraction in the range of physiological concentrations forming metal-complexes with copper and zinc cations may be factors that have cytostatic effect against S. aureus bacteria. Zinc cations realize bacteriostatic activity only in gamma-gloulin bound state whereas copper cations--also in the free state.

  12. Induction of an inhibitor antibody to factor XI in a patient with severe inherited factor XI deficiency by Rh immune globulin.

    Science.gov (United States)

    Zucker, Michal; Zivelin, Ariella; Teitel, Jerome; Seligsohn, Uri

    2008-02-01

    In this paper, we report an inhibitor antibody to factor XI (FXI) in a woman with severe inherited FXI deficiency, induced by FXI present in an Rh immune globulin preparation. The patient is homozygous for the Glu117Stop mutation, associated with a FXI level of less than 1 U/dL. Unlike all previously described patients with severe FXI deficiency and an inhibitor, the patient had never been exposed to blood products. Following 3 injections of Rh immune globulin during pregnancy, she developed an inhibitor to FXI (8 Bethesda units) that was shown to bind specifically to FXI and inhibit factor IX cleavage by purified FXIa. The administered Rh immune globulin and 2 other similar products were shown to contain FXI. Clinicians should be aware of the potential for immunization of severely FXI-deficient patients by FXI present in Rh immune globulin preparations.

  13. 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

  14. 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...

  15. Modulation in Wistar Rats of Blood Corticosterone Compartmentation by Sex and a Cafeteria Diet

    Science.gov (United States)

    Romero, María del Mar; Holmgren-Holm, Fredrik; Grasa, Maria del Mar; Esteve, Montserrat; Remesar, Xavier; Fernández-López, José Antonio; Alemany, Marià

    2013-01-01

    In the metabolic syndrome, glucocorticoid activity is increased, but circulating levels show little change. Most of blood glucocorticoids are bound to corticosteroid-binding globulin (CBG), which liver expression and circulating levels are higher in females than in males. Since blood hormones are also bound to blood cells, and the size of this compartment is considerable for androgens and estrogens, we analyzed whether sex or eating a cafeteria diet altered the compartmentation of corticosterone in rat blood. The main corticosterone compartment in rat blood is that specifically bound to plasma proteins, with smaller compartments bound to blood cells or free. Cafeteria diet increased the expression of liver CBG gene, binding plasma capacity and the proportion of blood cell-bound corticosterone. There were marked sex differences in blood corticosterone compartmentation in rats, which were unrelated to testosterone. The use of a monoclonal antibody ELISA and a polyclonal Western blot for plasma CBG compared with both specific plasma binding of corticosterone and CBG gene expression suggested the existence of different forms of CBG, with varying affinities for corticosterone in males and females, since ELISA data showed higher plasma CBG for males, but binding and Western blot analyses (plus liver gene expression) and higher physiological effectiveness for females. Good cross- reactivity to the antigen for polyclonal CBG antibody suggests that in all cases we were measuring CBG.The different immunoreactivity and binding affinity may help explain the marked sex-related differences in plasma hormone binding as sex-linked different proportions of CBG forms. PMID:23451210

  16. 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...

  17. Interaction between non-psychotropic cannabinoids in marihuana: effect of cannabigerol (CBG) on the anti-nausea or anti-emetic effects of cannabidiol (CBD) in rats and shrews.

    Science.gov (United States)

    Rock, Erin M; Goodwin, Jennifer M; Limebeer, Cheryl L; Breuer, Aviva; Pertwee, Roger G; Mechoulam, Raphael; Parker, Linda A

    2011-06-01

    The interaction between two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), which have been reported to act as a 5-hydroxytryptamine 1A (5-HT(1A)) agonist and antagonist, respectively, was evaluated. To evaluate the potential of CBG to reverse the anti-nausea, anti-emetic effects of CBD. In experiment 1, rats were pre-treated with CBG (0.0, 1, 5, and 10 mg/kg, ip), 15 min prior to being treated with CBD (experiment 1a: VEH or 5 mg/kg, ip) or 8-OH-DPAT (experiment 1b: VEH or 0.01 mg/kg, ip). Thirty minutes later, all rats received a pairing of 0.1% saccharin solution and LiCl (20 ml/kg of 0.15 M, ip). Seventy-two hours later, the rats received a drug-free taste reactivity test with saccharin to evaluate the effects of the treatments on the establishment of conditioned gaping reactions (a model of nausea). As well, conditioned saccharin avoidance was measured. In experiment 2, Suncus murinus were injected with CBG (5 mg/kg, ip) or VEH 15 min prior to CBD (5 mg/kg) or VEH and 30 min later were injected with LiCl (60 ml/kg of 0.15 M, i.p.), and the number of vomiting episodes were measured. CBD (5 mg/kg) suppressed conditioned gaping in rats and vomiting in shrews, which were reversed by pre-treatment with all doses of CBG. CBG also prevented the anti-nausea effects of 8-OH-DPAT. Interactions between moderate doses of CBG and CBD may oppose one another at the 5-HT(1A) receptor in the regulation of nausea and vomiting.

  18. 21 CFR 660.50 - Anti-Human Globulin.

    Science.gov (United States)

    2010-04-01

    ... which shall consist of one or more antiglobulin antibodies identified in § 660.55(d). (b) Source. The... globulins or protein-rich fluids derived from stable immunoglobulin-secreting cell lines maintained either...

  19. 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.

  20. 21 CFR 862.1330 - Globulin test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Globulin test system. 862.1330 Section 862.1330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

  1. 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

  2. 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 ...

  3. 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 ...

  4. Plasma Levels of Total Proteins, Albumin, Globulin and Plasma ...

    African Journals Online (AJOL)

    Plasma levels of total protein, albumin and globulin were estimated in 25 HIV positive subjects and 25 age and sex-matched controls. Test subjects were recruited from the Haematology day Clinic and Medical wards of the. OAUTHC, lle-Ife. The controls were equally obtained from staff and students within the OAUTHC, ...

  5. 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...... suggest a reduced rate of death from any cause, but the trials have been small and have varied in quality....

  6. 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...

  7. 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... which is safe for subcutaneous and intramuscular injection and (4) not to transmit viral hepatitis. (b...

  8. 21 CFR 866.5160 - Beta-globulin immunolog-ical test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-globulin immunolog-ical test system. 866.5160... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5160 Beta-globulin immunolog-ical test system. (a) Identification. A beta-globulin immunological test system is a...

  9. Pregnancy discovered after smallpox vaccination: Is vaccinia immune globulin appropriate?

    Science.gov (United States)

    Napolitano, Peter G; Ryan, Margaret A K; Grabenstein, John D

    2004-12-01

    Smallpox vaccination just before conception or during pregnancy can result, in rare instances, in fetal vaccinia from viral infection of the fetus. Approximately 50 cases have been documented, despite literally billions of people having been vaccinated. This live viral vaccine has a wider array of rare but serious medical side effects (eg, eczema vaccinatum, progressive vaccinia, encephalitis, myopericarditis) compared with other vaccines that are given currently to the public. In response to recent world events, the Centers for Disease Control and Prevention and the United States Department of Defense established a preoutbreak smallpox vaccination program. Because no actual outbreak has yet occurred, some investigators have proposed prophylactic treatment with vaccinia immune globulin for pregnancies that are exposed to smallpox vaccine to prevent fetal vaccinia. We review the existing medical literature to access the risks of fetal vaccinia in these pregnancies and the controversy regarding the prophylactic use of vaccinia immune globulin.

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

    OpenAIRE

    Roider, Tobias; Katzfu?, Michael; Matos, Carina; Singer, Katrin; Renner, Kathrin; Oefner, Peter J.; Dettmer-Wilde, Katja; Herr, Wolfgang; Holler, Ernst; Kreutz, Marina; Peter, Katrin

    2016-01-01

    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 intermediat...

  11. Genome Sequence of Azospirillum brasilense CBG497 and Comparative Analyses of Azospirillum Core and Accessory Genomes provide Insight into Niche Adaptation

    Science.gov (United States)

    Wisniewski-Dyé, Florence; Lozano, Luis; Acosta-Cruz, Erika; Borland, Stéphanie; Drogue, Benoît; Prigent-Combaret, Claire; Rouy, Zoé; Barbe, Valérie; Mendoza Herrera, Alberto; González, Victor; Mavingui, Patrick

    2012-01-01

    Bacteria of the genus Azospirillum colonize roots of important cereals and grasses, and promote plant growth by several mechanisms, notably phytohormone synthesis. The genomes of several Azospirillum strains belonging to different species, isolated from various host plants and locations, were recently sequenced and published. In this study, an additional genome of an A. brasilense strain, isolated from maize grown on an alkaline soil in the northeast of Mexico, strain CBG497, was obtained. Comparative genomic analyses were performed on this new genome and three other genomes (A. brasilense Sp245, A. lipoferum 4B and Azospirillum sp. B510). The Azospirillum core genome was established and consists of 2,328 proteins, representing between 30% to 38% of the total encoded proteins within a genome. It is mainly chromosomally-encoded and contains 74% of genes of ancestral origin shared with some aquatic relatives. The non-ancestral part of the core genome is enriched in genes involved in signal transduction, in transport and in metabolism of carbohydrates and amino-acids, and in surface properties features linked to adaptation in fluctuating environments, such as soil and rhizosphere. Many genes involved in colonization of plant roots, plant-growth promotion (such as those involved in phytohormone biosynthesis), and properties involved in rhizosphere adaptation (such as catabolism of phenolic compounds, uptake of iron) are restricted to a particular strain and/or species, strongly suggesting niche-specific adaptation. PMID:24705077

  12. Genome Sequence of Azospirillum brasilense CBG497 and Comparative Analyses of Azospirillum Core and Accessory Genomes provide Insight into Niche Adaptation

    Directory of Open Access Journals (Sweden)

    Victor González

    2012-09-01

    Full Text Available Bacteria of the genus Azospirillum colonize roots of important cereals and grasses, and promote plant growth by several mechanisms, notably phytohormone synthesis. The genomes of several Azospirillum strains belonging to different species, isolated from various host plants and locations, were recently sequenced and published. In this study, an additional genome of an A. brasilense strain, isolated from maize grown on an alkaline soil in the northeast of Mexico, strain CBG497, was obtained. Comparative genomic analyses were performed on this new genome and three other genomes (A. brasilense Sp245, A. lipoferum 4B and Azospirillum sp. B510. The Azospirillum core genome was established and consists of 2,328 proteins, representing between 30% to 38% of the total encoded proteins within a genome. It is mainly chromosomally-encoded and contains 74% of genes of ancestral origin shared with some aquatic relatives. The non-ancestral part of the core genome is enriched in genes involved in signal transduction, in transport and in metabolism of carbohydrates and amino-acids, and in surface properties features linked to adaptation in fluctuating environments, such as soil and rhizosphere. Many genes involved in colonization of plant roots, plant-growth promotion (such as those involved in phytohormone biosynthesis, and properties involved in rhizosphere adaptation (such as catabolism of phenolic compounds, uptake of iron are restricted to a particular strain and/or species, strongly suggesting niche-specific adaptation.

  13. 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.)

  14. 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.

  15. The effect of 60Co gamma radiation on human serum gamma-globulin

    International Nuclear Information System (INIS)

    Portakal, S.

    1984-01-01

    The effect of 60 Co gamma radiation on human serum gamma-globulin was studied in vitro experiments. Solutions of 0.5 percent gamma-globulin were exposed to 0.2, 0.5, 1.0 and 1.9 Mrad doses 60 Co gamma irradiation. Experiments showed that electrophoretic mobility of serum gamma-globulin decreased after gamma irradiation. No significant change in gamma-globulin UV absorption spectrum was observed at 0.2, 0.5, 1.0 and 1.9 Mrad doses. Gamma-globulin becomes progressively less soluble in water as the radiation doses is increased. Radiation induced transformation into insoluble gamma-globulin agregates and scission products. (author)

  16. Prophylactic effect of administration of human gamma globulins in a mouse model of tuberculosis.

    Science.gov (United States)

    Olivares, Nesty; Puig, Alina; Aguilar, Diana; Moya, Aniel; Cádiz, Armando; Otero, Oscar; Izquierdo, Luis; Falero, Gustavo; Solis, Rosa L; Orozco, Hector; Sarmiento, Maria E; Norazmi, Mohd Nor; Hernández-Pando, Rogelio; Acosta, Armando

    2009-05-01

    The protective effect of human gamma globulins on Mycobacterium tuberculosis infection was evaluated in a mouse model of intratracheal infection. Animals receiving human gamma globulins intranasally, 2h before intratracheal challenge showed a significant decrease in lung bacilli load compared to non-treated animals in different time intervals of up to 2 months after challenge. The same effect was obtained when M. tuberculosis was pre-incubated with the gamma globulin before challenge. The protective effect of the gamma-globulin formulation was abolished after pre-incubation with M. tuberculosis. These results suggest a potential role of specific antibodies in the defence against mycobacterial infections.

  17. Gender differences in the associations between cortisol and insulin in healthy subjects

    NARCIS (Netherlands)

    Stolk, RP; Lamberts, SWJ; deJong, FH; Pols, HAP; Grobbee, DE

    To investigate the role of cortisol in the etiology of insulin resistance in men and women, we examined 218 healthy non-hospitalized elderly, selected from the Rotterdam Study. Free cortisol was assessed by the ratio of fasting serum cortisol over corticosteroid-binding globulin (CBG), and insulin

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

    Science.gov (United States)

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

    1995-04-01

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

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

    Science.gov (United States)

    Roider, Tobias; Katzfuß, Michael; Matos, Carina; Singer, Katrin; Renner, Kathrin; Oefner, Peter J; Dettmer-Wilde, Katja; Herr, Wolfgang; Holler, Ernst; Kreutz, Marina; Peter, Katrin

    2016-12-11

    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.

  1. 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.

  2. 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.

  3. Serum globulin predicts all-cause mortality for life insurance applicants.

    Science.gov (United States)

    Fulks, Michael; Stout, Robert L; Dolan, Vera F

    2014-01-01

    Determine the relative mortality in apparently healthy adults with various levels of serum globulin. By use of the Social Security Death Master File, mortality in 2010 was determined for 7.7 million life insurance applicants age 20 to 89 providing blood samples with valid globulin results between 1992 and 2006. Relative mortality by Cox regression for bands of globulin values was determined by age-sex group, with age split into 20 to 59 and 60 to 89, with each grouping also including age as a covariate. Further analysis was conducted by excluding applicants with elevations of other test values associated with increased globulin levels and mortality risk. After accounting for the mortality impact of frequently associated laboratory test abnormalities including BMI, alkaline phosphatase and albumin, relative mortality was found to increase gradually for globulin values > 3.2 g/dL. Values > 4.0 were associated with a mortality risk that was approximately doubled. There is also a small increased risk for globulin values life insurance applicants. In many cases, other laboratory findings were not informative of the risk.

  4. Steroid Sex Hormones, Sex Hormone-Binding Globulin, and Diabetes Incidence in the Diabetes Prevention Program.

    Science.gov (United States)

    Mather, K J; Kim, C; Christophi, C A; Aroda, V R; Knowler, W C; Edelstein, S E; Florez, J C; Labrie, F; Kahn, S E; Goldberg, R B; Barrett-Connor, E

    2015-10-01

    Steroid sex hormones and SHBG may modify metabolism and diabetes risk, with implications for sex-specific diabetes risk and effects of prevention interventions. This study aimed to evaluate the relationships of steroid sex hormones, SHBG and SHBG single-nucleotide polymorphisms (SNPs) with diabetes risk factors and with progression to diabetes in the Diabetes Prevention Program (DPP). This was a secondary analysis of a multicenter randomized clinical trial involving 27 U.S. academic institutions. The study included 2898 DPP participants: 969 men, 948 premenopausal women not taking exogenous sex hormones, 550 postmenopausal women not taking exogenous sex hormones, and 431 postmenopausal women taking exogenous sex hormones. Participants were randomized to receive intensive lifestyle intervention, metformin, or placebo. Associations of steroid sex hormones, SHBG, and SHBG SNPs with glycemia and diabetes risk factors, and with incident diabetes over median 3.0 years (maximum, 5.0 y). T and DHT were inversely associated with fasting glucose in men, and estrone sulfate was directly associated with 2-hour post-challenge glucose in men and premenopausal women. SHBG was associated with fasting glucose in premenopausal women not taking exogenous sex hormones, and in postmenopausal women taking exogenous sex hormones, but not in the other groups. Diabetes incidence was directly associated with estrone and estradiol and inversely with T in men; the association with T was lost after adjustment for waist circumference. Sex steroids were not associated with diabetes outcomes in women. SHBG and SHBG SNPs did not predict incident diabetes in the DPP population. Estrogens and T predicted diabetes risk in men but not in women. SHBG and its polymorphisms did not predict risk in men or women. Diabetes risk is more potently determined by obesity and glycemia than by sex hormones.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    of the kallikrein system or the complement system and cellular studies showed no toxic effects on a variety of human cell lines. In vivo studies showed no acute toxic effects in mice, rats or guinea pigs upon intravenous infusion. A 14-day local tolerance study in rabbits showed no adverse effects, and 14-day...

  6. 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)

  7. 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.......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....

  8. 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....

  9. 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

  10. 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

  11. Interaction of Soybean 7S Globulin Peptide with Cell Membrane Model via ITC, QCM-D and Langmuir Monolayer Study.

    Science.gov (United States)

    Zou, Yuan; Pan, Run-Ting; Ruan, Qi-Jun; Wan, Zhili; Guo, Jian; Yang, Xiao-Quan

    2018-04-10

    To understand an underlying molecular mechanism on 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 enterocyte.

  12. 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.

  13. Total Protein and Albumin/Globulin Ratio Test

    Science.gov (United States)

    ... and Iron-binding Capacity (TIBC, UIBC) Trichomonas Testing Triglycerides Troponin Tryptase Tumor Markers Uric Acid Urinalysis Urine ... as a source of amino acids for tissue metabolism, and as the principle component involved in maintaining ...

  14. Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Δ⁹-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour.

    Science.gov (United States)

    Deiana, Serena; Watanabe, Akihito; Yamasaki, Yuki; Amada, Naoki; Arthur, Marlene; Fleming, Shona; Woodcock, Hilary; Dorward, Patricia; Pigliacampo, Barbara; Close, Steve; Platt, Bettina; Riedel, Gernot

    2012-02-01

    Phytocannabinoids are useful therapeutics for multiple applications including treatments of constipation, malaria, rheumatism, alleviation of intraocular pressure, emesis, anxiety and some neurological and neurodegenerative disorders. Consistent with these medicinal properties, extracted cannabinoids have recently gained much interest in research, and some are currently in advanced stages of clinical testing. Other constituents of Cannabis sativa, the hemp plant, however, remain relatively unexplored in vivo. These include cannabidiol (CBD), cannabidivarine (CBDV), Δ(9)-tetrahydrocannabivarin (Δ(9)-THCV) and cannabigerol (CBG). We here determined pharmacokinetic profiles of the above phytocannabinoids after acute single-dose intraperitoneal and oral administration in mice and rats. The pharmacodynamic-pharmacokinetic relationship of CBD (120 mg/kg, ip and oral) was further assessed using a marble burying test in mice. All phytocannabinoids readily penetrated the blood-brain barrier and solutol, despite producing moderate behavioural anomalies, led to higher brain penetration than cremophor after oral, but not intraperitoneal exposure. In mice, cremophor-based intraperitoneal administration always attained higher plasma and brain concentrations, independent of substance given. In rats, oral administration offered higher brain concentrations for CBD (120 mg/kg) and CBDV (60 mg/kg), but not for Δ(9)-THCV (30 mg/kg) and CBG (120 mg/kg), for which the intraperitoneal route was more effective. CBD inhibited obsessive-compulsive behaviour in a time-dependent manner matching its pharmacokinetic profile. These data provide important information on the brain and plasma exposure of new phytocannabinoids and guidance for the most efficacious administration route and time points for determination of drug effects under in vivo conditions.

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

    Science.gov (United States)

    Lee, Hye-Jung; Jo, Yeong-Min; Lee, Jong-Yeol; Lim, Sun-Hyung; Kim, Young-Mi

    2015-06-30

    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.

  16. 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.

  17. 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

  18. Prevention of postherpetic neuralgia with varicella-zoster hyperimmune globulin.

    Science.gov (United States)

    Hügler, Peter; Siebrecht, Peter; Hoffmann, Klaus; Stücker, Markus; Windeler, Jürgen; Altmeyer, Peter; Laubenthal, Heinz

    2002-01-01

    Recovery after an acute attack of herpes zoster is followed by postherpetic neuralgia (PHN) in 9-14% of all patients. Depending on the patient's age, the severity of the acute attack of herpes zoster and the dermatome involved, the incidence of PHN may be as high as 65%. The purpose of our study was to ascertain the incidence of PHN after a prophylactic intravenous injection of varicella-zoster hyperimmune globulin (VZV-IG) (Varitect Biotest Pharma). For this double-blind placebo-controlled randomised investigation we defined PHN as pain confined to the dermatome previously affected by herpes zoster, and we required a pain intensity of at least 15% points on a visual analogue scale (VAS) for this dermatome. The inclusion criteria were the dermatological diagnosis of herpes zoster together with age over 50 years. On Day 1, 20 patients received a single intravenous infusion of VZV-IG in a dose of 2mL/kg body weight, 20 patients (control group) received a single infusion of human albumin 5% in a dose of 2mL/kg body weight. All patients received acyclovir intravenously in a dose of 15mg/kg body weight per 24h for 5 days. The patients were followed up for a total of 42 days. The incidence of PHN at Day 42 was selected as the main outcome criterion for assessing the efficacy of prophylaxis. On reaching a significant difference between the groups (t test; alphaVAS and a NAS. As auxiliary outcome criteria, we used the McGill Pain-Rating Questionnaire in its German version, the revised multidimensional pain scale (RMSS) and the Freiburg symptom list (FBL). All results were assessed by the t test (alpha<0.05). The frequency of PHN in the placebo group was 70% (14/20), in the active treatment group it was 35% (7/20) at Day 42. The results of the McGill test showed the variability of the perception of pain in the placebo group significantly greater. No significant group differences were found in the FBL. Being tested with the RMSS, the patients of the placebo group assessed

  19. Long-term outcome after immunosuppressive therapy with horse or rabbit antithymocyte globulin and cyclosporine for severe aplastic anemia in children.

    Science.gov (United States)

    Jeong, Dae Chul; Chung, Nack Gyun; Cho, Bin; Zou, Yao; Ruan, Min; Takahashi, Yoshiyuki; Muramatsu, Hideki; Ohara, Akira; Kosaka, Yoshiyuki; Yang, Wenyu; Kim, Hack Ki; Zhu, Xiaofan; Kojima, Seiji

    2014-04-01

    Some prospective studies showed that rabbit antithymocyte globulin was inferior to horse antithymocyte globulin as first-line therapy for patients with severe aplastic anemia. We retrospectively analyzed the clinical outcome of 455 children with severe aplastic anemia who received horse antithymocyte globulin (n=297) or rabbit antithymocyte globulin (n=158) combined with cyclosporine as first-line therapy between 1992 and 2010. The response rates were comparable between the horse and rabbit antithymocyte globulin groups at 3 months [46% (136/294) versus 42% (66/153), P=0.55] and 6 months [60% (178/292) versus 55% (87/143), P=1.0]. Using multivariate analysis, differences in antithymocyte globulin preparations were not associated with response rates. However, 2-year and 10-year overall survival rates in the horse antithymocyte globulin group were significantly better than those in the rabbit antithymocyte globulin group (2-year overall survival: 96% versus 87%, 10-year overall survival: 92% versus 84%, P=0.004). On the basis of multivariate analysis, use of rabbit antithymocyte globulin was a significant adverse factor for overall survival (hazard ratio = 3.56, 95% confidence interval, 1.53 - 8.28, P=0.003). Rabbit antithymocyte globulin caused more profound immunosuppression, which might be responsible for the higher incidence of severe infections. Considering that there are no studies showing the superiority of rabbit antithymocyte globulin over horse antithymocyte globulin, horse antithymocyte globulin should be recommended as a first-line therapy. However, our results justify the use of rabbit antithymocyte globulin as first-line therapy if horse antithymocyte globulin is not available.

  20. The effect of the administration of human gamma globulins in a model of BCG infection in mice.

    Science.gov (United States)

    Olivares, Nesty; León, Annette; López, Yamilé; Puig, Alina; Cádiz, Armando; Falero, Gustavo; Martínez, Máximo; Sarmiento, Marie E; Fariñas, Mildrey; Infante, Juan F; Sierra, Gustavo; Solís, Rosa L; Acosta, Armando

    2006-01-01

    The effect of the administration of a commercial preparation of human gamma globulins has been evaluated in a mouse model of intranasal infection with BCG. First, we demonstrated the passage of specific antibodies to saliva and lung lavage following the intranasal or intraperitoneal administration to mice of human gamma globulins. This treatment of mice inhibited BCG colonization of the lungs (p < 0.01). A similar inhibitory effect was observed after infection of mice with gamma globulin opsonized BCG organisms (p < 0.01). These results are relevant for the development of new strategies for the control and treatment of tuberculosis.

  1. 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.

  2. 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...

  3. Immunotherapy of acute radiation syndromes with antiradiation gamma G globulin.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Vecheslav; Casey, Rachael; Jones, Jeffrey; Kedar, Prasad

    Introduction: If an immunotherapy treatment approach to treatment of acute radiation syndromes (ARS) were to be developed; consideration could be given to neutralization of radiation toxins (Specific Radiation Determinants- SRD) by specific antiradiation antibodies. To accomplish this objective, irradiated animals were injected with a preparation of antiradiation immunoglobulin G (IgG) obtained from hyperimmune donors. Radiation-indeced toxins that we call Specific Radiation Determinants (SRD) possess toxic (neurotoxic, haemotoxic and enterotoxic) characteristics as well as specific antigenic properties that combined with the direct physiochemical direct radiation damage, induce the development of many of the pathological processes associated with ARS. We tested several specific hyperimmune IgG preparations against these radiation toxins and observed that their toxic properties were neutralized by specific antiradiation IgGs. Material and Methods: Rabbits were inoculated with SRD radiation toxins to induce hyperimmune serum. The hyperimmune serum was pooled from several animals, purified, and concentrated. Enzyme-linked immunosorbent assays of the hyperimmune serum revealed high titers of IgG with specific binding to radiation toxins. The antiradiation IgG preparation was injected into laboratory animals one hour before and three hours after irradiation, and was evaluated for its ability to protect inoculated animals against the development of acute radiation syndromes. Results: Animals that were inoculated with specific antiradiation antibodies before receiving lethal irradiation at LD 100/30 exhibited 60-75% survival rate at 30 days, whereas all control animals expired by 30 days following exposure. These inoculated animals also exhibited markedly reduced clinical symptoms of ARS, even those that did not survive irradiation. Discussion: The results of our experiments demonstrate that rabbit hyperimmune serum directed against SRD toxins afford significant, albeit

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

    Science.gov (United States)

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

    2013-12-01

    A 1-year-old boy developed autoimmune hemolytic anemia after a negative direct anti-globulin test. The concentration of erythrocyte membrane-associated immunoglobulin G, determined using an immunoradiometric assay, correlated with disease activity. He was positive for cytomegalovirus (CMV) both serologically and by quantitative real-time polymerase chain reaction, indicating that his autoimmune hemolytic anemia was directly caused by CMV infection. Since anti-CMV immunoglobulin G was not absorbed by the patient's erythrocytes, cross-reaction between erythrocyte antigens and CMV was not likely a causative factor for hemolysis. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  5. Belatacept conversion in an HIV-positive kidney transplant recipient following anti-thymocyte globulin induction.

    Science.gov (United States)

    Kuten, Samantha A; Patel, Samir J; Baru, Ashvin; Gaber, A Osama; Crutchley, Rustin D; Ramanathan, Venkataraman; Knight, Richard J

    2017-10-01

    Herein, we describe a case of early belatacept conversion in a human immunodeficiency virus (HIV)-positive kidney transplant recipient in an effort to improve suboptimal graft function and avoid drug interactions following anti-thymocyte globulin (ATG) administration. We observed improvement in renal function without HIV disease progression or opportunistic infections. Donor-specific antibodies appeared shortly after conversion but cleared without intervention. This case highlights belatacept as a means to improve renal function and avoid significant drug interactions even following ATG induction. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. 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

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Andress L

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Patchaya Boonchaya-anant

    2016-01-01

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

  10. 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, ...

  11. 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

  12. 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

  13. 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.

  14. Giant Cell Myocarditis with Incessant Ventricular Arrhythmias Treated Successfully with Methylprednisolone and Rat Antithymocyte Globulin

    Directory of Open Access Journals (Sweden)

    Mudassar Baig

    2011-01-01

    Full Text Available Giant cell myocarditis is an aggressive form of this condition that is typically progressive and unresponsive to usual medical treatment. Here, we describe a 34-year-old patient presenting with incessant ventricular arrhythmias with hemodynamic compromise who required prolonged support in intensive care with an intra-aortic balloon pump (IABP. His Coronary arteries were normal and LV endomyocardial biopsy revealed myocyte necrosis with inflammatory infiltrate of lymphocytes, eosinophils, and giant cells suggestive of giant cell myocarditis. He was successfully treated with pulsed intravenous methylprednisolone and rat antithymocyte globulin (RATG. Despite a good functional cardiac recovery, some months later he developed a fluctuant neck swelling which fine needle aspiration confirmed as tuberculosis.

  15. [Micro-column gel indirect anti-globulin technique for screening and identification of irregular antibody].

    Science.gov (United States)

    Ma, Shu-Xuan; Liu, Jing-Han; Li, Xi-Jin; Luo, Qun; Chen, Min-Cai; Wang, Hai-Jun

    2003-04-01

    The purpose of this study was to design an antibody screening method based on the micro-column gel indirect anti-globulin technique (MGIAT), using pooled cells and plasma, by comparison with the conventional indirect anti-globulin technique (CIAT) combined with a two-stage papain technique, and to explore the feasibility of the use of plasma instead of serum as test material. The samples of blood recipients in our hospital were screened for irregular antibody using pooled test cells. Screening of the antibodies was identified both by MGIAT and CIAT combined papain technique respectively. The results showed that the irregular erythrocyte antibodies were detected in 20 cases from 5,000 recipients screened by MGIAT, using pooled cells, the positive rate was 0.4%. The specificity of 20 cases of irregular antibodies was as follows: 2 cases of anti-D, 8 cases of anti-E, 1 cases of anti-C, 2 cases of anti-c, 2 cases of anti-Mi(a), 2 cases of anti-Jk(a), 1 case of anti-Le(a) and 2 cases of anti-Fy(a). Antibody was detected from 19 cases using CIAT. Anti-Le(a) was detected with adding complement from Le(a-b-) person. Only 13 cases antibody were found by papain technique. It was concluded that irregular antibody screening by MGIAT using pooled cells can take place of the CIAT combining with papain technique in clinical application. Plasma is superior to serum in antibody screening test.

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

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    Xue-Li Gao

    2016-01-01

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

  17. Enrichment and identification of the most abundant zinc binding proteins in developing barley grains by Zinc-IMAC capture and nano LC-MS/MS

    DEFF Research Database (Denmark)

    Dionisio, Giuseppe; Uddin, Mohammad Nasir; Vincze, Eva

    2018-01-01

    , 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...

  18. 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

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

    Science.gov (United States)

    James, Andrew T; Yang, Aijun

    2016-03-01

    The content and globulin subunit composition of soybean proteins are known to affect tofu quality and food-grade soybeans usually have higher levels of proteins. We studied the tofu quality of soybeans with high (44.8%) or low (39.1%) protein content and with or without the 11S globulin polypeptide, 11SA4. Both protein content and 11SA4 significantly affected tofu gel properties. Soybeans containing more protein had smaller seeds which produced significantly firmer (0.663 vs.0.557 N, pprotein subunits, which may have contributed to the improvement in tofu gel properties. These results suggest that, in combination with higher protein content, certain protein subunits or their polypeptides can also be targeted in selecting soybeans to further improve soy food quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. α2u-globulins mediate manipulation of host attractiveness in Toxoplasma gondii-Rattus novergicus association.

    Science.gov (United States)

    Vasudevan, Anand; Kumar, Vineet; Chiang, Yin Ning; Yew, Joanne Y; Cheemadan, Sabna; Vyas, Ajai

    2015-09-01

    Uninfected female rats (Rattus novergicus) exhibit greater attraction to the males infected with protozoan parasite Toxoplasma gondii. This phenomenon is contrary to the aversion towards infected males observed in multitude of other host-parasite associations. In this report, we describe a proximate mechanism for this anomaly. We demonstrate that T. gondii infection enhances hepatic production and urinary excretion of α2u-globulins in rats. We further demonstrate that α2u-globulins are sufficient to recapitulate male sexual attractiveness akin to effects of the infection. This manipulation possibly results in greater horizontal transmission of this parasite between the infected male and the uninfected female. It supports the notion that in some evolutionary niches parasites can alter host sexual signaling, likely leading to an increased rate of sexual transmission.

  1. 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.

  2. Rabbit anti-thymocyte globulin induction therapy does not prolong survival after lung transplantation.

    Science.gov (United States)

    Hartwig, Matthew G; Snyder, Laurie D; Appel, James Z; Cantu, Ed; Lin, Shu S; Palmer, Scott M; Davis, R Duane

    2008-05-01

    Lung transplant survival is limited by the development of bronchiolitis obliterans syndrome (BOS). The strongest risk factor for BOS is acute rejection (AR). We have previously shown that rabbit anti-thymocyte globulin (RATG) induction therapy is associated with a decrease in early AR. Thus, we hypothesized that RATG induction would translate to reduced BOS and improved long-term graft survival. Forty-four lung recipients were prospectively randomized to receive conventional immunosuppression with RATG induction (RATG group) or conventional immunosuppression alone (control group). End-points included graft survival, early and total acute rejection, BOS and treatment complications. There was no difference in graft survival between the groups at 8 years (RATG: 36%; control: 23%; p = 0.48). The RATG group had fewer early rejections compared with the control group (5% vs 41%; p = 0.01). However, the overall rejection incidence did not differ (RATG: 62%; control: 68%; p = 0.52). There was a trend toward a delay in BOS onset among RATG subjects compared with control subjects (2,376 days vs 1,108 days; log rank, p = 0.15). There was no difference in the incidence of infections, but the RATG group had a higher rate of malignancies. Our results suggest that alternative approaches to anti-thymocyte induction should be pursued to reduce BOS and prolong allograft survival.

  3. 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%; pGrafalon-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.

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

    Science.gov (United States)

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

    2012-01-01

    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. To investigate wound healing complications after ATG therapy in renal transplant recipients. The medical records of 333 kidney transplant recipients were assessed for wound healing disorders. Among these patients, 92 received ATG and 5 doses of 1.5 mg/kg ATG along with the standard protocol of drugs. The mean age of patients was 38.9 years. Of 333 recipients, 92 (23.7%) received ATG; 21 (6.3%) developed wound healing complications. There was a significant relationship between ATG therapy and wound complications (p=0.034). Also, women were more likely to develop wound healing disorders than men (p=0.002). No statistical difference was observed between age and wound healing complication (p=0.28). There was no significant difference between the mean duration of hospitalization between ATG and Non-ATG group (p=0.9). ATG increases the risk of overall wound complications. It is needed to pay more attention to the patients treated with this immunosuppressant to avoid the risk of re-interventions, lessen the duration of hospitalization and decrease the impairment of graft function.

  5. 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.

  6. [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) (Pgravis. At the multivariate Cox regression analysis, the AGR (Pgravis 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 (Pgravis.

  7. 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

  8. 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

  9. Surface characterization of 7S and 11S globulin powders from soy protein examined by X-ray photoelectron spectroscopy and scanning electron microscopy.

    Science.gov (United States)

    Zhao, Xiaoyan; Chen, Jun; Zhu, Qingjun; Du, Fangling; Ao, Qiang; Liu, Jie

    2011-09-01

    In this study the surface composition of 7S and 11S globulin powders from soybean proteins by aqueous buffer and reverse micelle extractions had been examined using X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Analysis by XPS revealed that the O and N atomic percentage of 7S and 11S globulin surfaces from bis(2-ethylhexyl) sodium sulfosuccinate (AOT) reverse micelle was higher than from aqueous buffer, but the C atomic percentage was lower. The O/C ratio of the 7S globulin powder from aqueous buffer and reverse micelle was similar while significant differences were obtained in the O/C ratio of the 11S globulin powder, N/C atom ratios of the 7S and 11S globulin powders and high-resolution XPS C 1s, N 1s, O 1s spectra. Powder microstructure after reverse micelle treatment showed the presence of small pores, indicating the effect of reverse micelle on the 7S and 11S globulin structure. The obtained results indicated that the reverse micelle could affect the C, O and N components on the surface of soybean proteins. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Genome-wide association studies with proteomics data reveal genes important for synthesis, transport and packaging of globulins in legume seeds.

    Science.gov (United States)

    Le Signor, Christine; Aimé, Delphine; Bordat, Amandine; Belghazi, Maya; Labas, Valérie; Gouzy, Jérôme; Young, Nevin D; Prosperi, Jean-Marie; Leprince, Olivier; Thompson, Richard D; Buitink, Julia; Burstin, Judith; Gallardo, Karine

    2017-06-01

    Improving nutritional seed quality is an important challenge in grain legume breeding. However, the genes controlling the differential accumulation of globulins, which are major contributors to seed nutritional value in legumes, remain largely unknown. We combined a search for protein quantity loci with genome-wide association studies on the abundance of 7S and 11S globulins in seeds of the model legume species Medicago truncatula. Identified genomic regions and genes carrying polymorphisms linked to globulin variations were then cross-compared with pea (Pisum sativum), leading to the identification of candidate genes for the regulation of globulin abundance in this crop. Key candidates identified include genes involved in transcription, chromatin remodeling, post-translational modifications, transport and targeting of proteins to storage vacuoles. Inference of a gene coexpression network of 12 candidate transcription factors and globulin genes revealed the transcription factor ABA-insensitive 5 (ABI5) as a highly connected hub. Characterization of loss-of-function abi5 mutants in pea uncovered a role for ABI5 in controlling the relative abundance of vicilin, a sulfur-poor 7S globulin, in pea seeds. This demonstrates the feasibility of using genome-wide association studies in M. truncatula to reveal genes that can be modulated to improve seed nutritional value. © 2017 INRA. New Phytologist © 2017 New Phytologist Trust.

  11. 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.

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

    Science.gov (United States)

    Miles, Judith H; Takahashi, T Nicole

    2007-07-01

    Though causes of autism are considered largely genetic, considerable concern remains that exposure to Rh immune globulin (RhIg), which until 2001 in the United States contained the preservative thimerosal, can cause autism. To determine whether mothers of children with autism are more likely to be Rh negative (Rh(-)) or to have received RhIg preserved with thimerosal, which is 49.6% ethyl mercury, we surveyed families of children with an autism spectrum disorder (ASD) ascertained through a University-based autism clinic considered free of ascertainment biases related to type of autism or severity. Between 2004 and 2006, 305 mothers of 321 children with an ASD agreed to participate in a telephone interview. Analysis of complete records including the blood group status and RhIg exposure of 214 families showed that Rh(-) status is no higher in mothers of children with autism than in the general population, exposure to antepartum RhIg, preserved with thimerosal is no higher for children with autism and pregnancies are no more likely to be Rh incompatible. This was also true for autism subgroups defined by behavioral phenotype, gender, IQ, regressive onset, head circumference, dysmorphology, birth status, essential, or complex phenotype. These findings support the consensus that exposure to ethylmercury in thimerosal is not the cause of the increased prevalence of autism. These data are important not only for parents in this country but also for the international health community where thimerosal continues to be used to preserve multi-dose vials which in turn makes vaccines affordable. (c) 2007 Wiley-Liss, Inc.

  13. Rh(O)D immune globulin products for prevention of alloimmunization during pregnancy.

    Science.gov (United States)

    Aitken, Samuel L; Tichy, Eric M

    2015-02-15

    The pharmacologic properties of Rhesus (Rh) immune globulin (RhIG) and clinical data on its effectiveness in preventing Rh-antigen alloimmunization in pregnant women are reviewed. RhIG is a human plasma derivative that targets red blood cells (RBCs) positive for Rh(O) antigen (also called D antigen). In the United States and other countries, the widespread use of RhIG has markedly reduced the occurrence of hemolytic disease of the fetus and newborn (HDFN), a devastating condition caused by D-antigen sensitization of a pregnant woman via exposure to fetal RBCs (usually during detachment of the placenta in labor) that results in a maternal immune response leading to severe hemolysis in the fetus. Routine administration of RhIG at 26-30 weeks' gestation and again within 72 hours of delivery has been shown to be highly effective in preventing maternal Rh alloimmunization, with very low rates of D-antigen sensitization (in the range of 0-2.2%) reported in multiple studies of at-risk women. The four RhIG products currently available in the United States have common clinical indications but differ in certain attributes. Pharmacists can play an important role in guiding other clinicians on the rationale for the use of RhIG, important differences between products, and appropriate timing of RhIG therapy. Routine administration of RhIG to women at risk for Rh alloimmunization is clinically effective and has made HDFN a rare clinical event. The available RhIG products are not the same and should be carefully reviewed to ensure that they are administered safely. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  14. Anti-thymocyte globulin induces neoangiogenesis and preserves cardiac function after experimental myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Michael Lichtenauer

    Full Text Available RATIONALE: Acute myocardial infarction (AMI followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries. OBJECTIVE: Of relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG was evaluated in this study. METHODS AND RESULTS: AMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01. Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG. CONCLUSIONS: These data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI.

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

    Science.gov (United States)

    Grabenstein, John D

    2013-04-12

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

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Mária Baranyi

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

  18. Treatment with high-dose recombinant human hyaluronidase-facilitated subcutaneous immune globulins in patients with juvenile dermatomyositis who are intolerant to intravenous immune globulins: a report of 5 cases.

    Science.gov (United States)

    Speth, Fabian; Haas, Johannes-Peter; Hinze, Claas H

    2016-09-13

    High-dose intravenous immune globulins (IVIg) are frequently used in refractory juvenile dermatomyositis (JDM) but are often poorly tolerated. High-dose recombinant human hyaluronidase-facilitated subcutaneous immune globulins (fSCIg) allow the administration of much higher doses of immune globulins than conventional subcutaneous immune globulin therapy and may be an alternative to IVIg. The safety and efficacy of fSCIg therapy in JDM is unknown. In this retrospective case series, five patients with steroid-refractory severe JDM were treated with high-dose fSCIg due to IVIg adverse effects (severe headaches, nausea, vomiting, difficult venous access). Peak serum IgG levels, muscle enzymes, the childhood myositis assessment scale and adverse effects were retrieved for at least 6 months following intiation of fSCIg. Data were analyzed by descriptive statistics. Patients initially received fSCIg 1 g/kg every 14 days, resulting in median IgG peak levels of 1901 mg/dl (1606-2719 mg/dl), compared to median IgG peak and trough levels while previously receiving IVIg of 2741 mg/dl (2429-2849 mg/dl) and 1351 mg/dl (1156-1710 mg/dl). Additional antirheumatic therapies consisted of low-dose glucocorticoid therapy, methotrexate, mycophenolate mofetil and/or rituximab. Two patients maintained clinically inactive disease and three patients had only a partial treatment response. In the three patients with partial treatment response, fSCIg 1 g/kg was then given on days 1 and 6 of every 28-day cycle resulting in IgG peak levels of between 2300-2846 mg/dl (previously 1606-1901 mg/dl on the biweekly regimen), resulting in clinically inactive disease in two of the three patients. There were no relevant adverse effects that limited continuation of fSCIg treatment. High-dose fSCIg is well-tolerated in patients with JDM and high peak serum IgG levels can be achieved which may be important for treatment success. High-dose fSCIg may therefore be an alternative to high-dose IVIg

  19. Plasma electrophoretic profiles and hemoglobin binding protein reference intervals in the eastern box turtle (Terrapene carolina carolina) and influences of age, sex, season, and location.

    Science.gov (United States)

    Flower, Jennifer E; Byrd, John; Cray, Carolyn; Allender, Matthew C

    2014-12-01

    Evaluation of plasma electrophoretic profiles and acute phase protein concentrations may play a valuable role in health assessment of reptiles; however, little is known about reference intervals in free-ranging eastern box turtles (Terrapene carolina carolina). The purpose of this study was to establish reference intervals of protein electrophoretic profiles and hemoglobin binding protein ([HBP] as determined by a haptoglobin assay) in free-ranging eastern box turtles and to assess any possible correlations between varying age class (adults vs. juvenile), sex (male, female, or unknown), season (spring, summer, or fall), or location (Tennessee vs. Illinois). Blood samples were obtained from 324 eastern box turtles from 2010 to 2012 at three sites in Illinois and one site in Tennessee, USA. Significant differences were observed with total protein (sex, season, state, Illinois location), albumin (age class, season, state, Illinois location), α-1 globulins (sex, season, Illinois location), α-2 globulins (sex, season, state, Illinois location), β globulins (age class, sex, season, state, Illinois location), γ globulins (sex, season state, Illinois location), and hemoglobin binding protein (age class, sex, state, Illinois location). The use of electrophoretic profiles and acute phase proteins is a relatively new concept in reptilian medicine, and this study allowed for establishment of references intervals in the eastern box turtle and emphasized differences that occured based on age, sex, season, and location. Future research in this area can now build on these data to determine changes in population health over time or alterations due to specific environmental or disease threats.

  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. 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.

  2. Adsorptive properties of albumin, fibrinogen, and gamma-globulin on fluorinated diamond-like carbon films coated on PTFE.

    Science.gov (United States)

    Ozeki, K; Nagashima, I; Hirakuri, K K; Masuzawa, T

    2010-05-01

    Fluorinated diamond-like carbon (F-DLC) films were deposited on polytetrafluoroethylene (PTFE) using radio frequency (RF) plasma-enhanced chemical vapor deposition (CVD) by changing the ratio of tetrafluoromethane (CF(4)) and methane (CH(4)). To enhance the adhesion strength of the F-DLC film to the PTFE substrate, the PTFE surface was modified with a N(2) plasma pre-treatment. XPS analysis of the films showed that the C-C bond decreased with increases in the CF(4) ratio, whereas the C-F bond increased with the CF(4) ratio. The F/C ratio of the film also increased with the CF(4) ratio. The pull-out test showed that the adhesion strengths of the films (CF(4)-0-60%) were improved with the plasma pre-treatment. In the film without the plasma pre-treatment, adhesion strength increased with the CF(4) ratio. In contrast, in the case with the plasma pre-treatment, the adhesion strength of the F-DLC film decreased with the increased CF(4) ratio. Regarding the adsorption of albumin, fibrinogen, and gamma-globulin, the amount of adsorbed albumin on the film decreased with an increasing CF(4) ratio, and the amount of adsorbed fibrinogen and gamma-globulin increased with the CF(4) ratio. The CF(4)-0% DLC film showed the most adsorbed albumin and the least adsorbed fibrinogen and gamma-globulin. This indicates that the CF(4)-0% DLC film has higher anti-thrombogenicity than the F-DLC film.

  3. Progressive Vaccinia: Case Description and Laboratory-Guided Therapy With Vaccinia Immune Globulin, ST-246, and CMX001

    Science.gov (United States)

    Lederman, Edith R.; Davidson, Whitni; Groff, Harold L.; Smith, Scott K.; Warkentien, Tyler; Li, Yu; Wilkins, Kimberly A.; Karem, Kevin L.; Akondy, Rama S.; Ahmed, Rafi; Frace, Michael; Shieh, Wun-Ju; Zaki, Sherif; Hruby, Dennis E.; Painter, Wendy P.; Bergman, Kimberly L.; Cohen, Jeffrey I.; Damon, Inger K.

    2012-01-01

    Progressive vaccinia (PV) is a rare but potentially lethal complication that develops in smallpox vaccine recipients with severely impaired cellular immunity. We describe a patient with PV who required treatment with vaccinia immune globulin and who received 2 investigational agents, ST-246 and CMX001. We describe the various molecular, pharmacokinetic, and immunologic studies that provided guidance to escalate and then successfully discontinue therapy. Despite development of resistance to ST-246 during treatment, the patient had resolution of PV. This case demonstrates the need for continued development of novel anti-orthopoxvirus pharmaceuticals and the importance of both intensive and timely clinical and laboratory support in management of PV. PMID:22904336

  4. [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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. The calcineurin inhibitor tacrolimus allows the induction of functional CD4+CD25+ regulatory T cells by rabbit anti-thymocyte globulins

    NARCIS (Netherlands)

    V.D.K.D. Sewgobind (Varsha); L.J.W. van der Laan (Luc); M.M.L. Kho (Marcia); R. Kraaijeveld (Rens); S.S. Korevaar (Sander); W.M. Mol (Wendy)

    2010-01-01

    textabstractRabbit anti-thymocyte globulins (rATG) induce CD4+CD25 +forkhead box P3 (FoxP3+) regulatory T cells that control alloreactivity. In the present study, we investigated whether rATG convert T cells into functional CD4+CD25+FoxP3+CD127 -/low regulatory T cells in the presence of drugs that

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

    Science.gov (United States)

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

    2016-03-02

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

  11. 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.

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

    Science.gov (United States)

    Schimke, R; Bernstein, B; Ambrosius, H

    1977-01-01

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

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

    DEFF Research Database (Denmark)

    Merlino, Marielle; Bousbata, Sabrina; Svensson, Birte

    2012-01-01

    in endosperm proteins due to chromosomal deletions. This differential analysis of spots allowed structural or regulatory genes, encoding 211 proteins, to be located on segments of the 21 wheat chromosomes. In addition, variance analysis of quantitative variations in spot volume showed that the expression......Albumins and globulins from the endosperm of Triticum aestivum L. cv Chinese Spring (CS) were analysed to establish a proteome reference map for this standard wheat cultivar. Approximately, 1,145 Coomassie-stained spots were detected by two-dimensional gel electrophoresis (2DE), 410 of which were...... identified using mass spectrometry and data mining. Salt-soluble endosperm proteins from 67 CS deletion lines were also separated by 2DE (four gels per line). Image analysis of the 268 2DE gels as compared to the CS reference proteome allowed the detection of qualitative and quantitative variations...

  14. In vivo release of testosterone from γ-globulin-drug delivery composites made by radiation after melt-pressing

    International Nuclear Information System (INIS)

    Asano, Masaharu; Yoshida, Masaru; Kaetsu, Isao; Nakai, Katsuyuki; Yamanaka, Hidetoshi; Yuasa, Hisako; Shida, Keizo.

    1983-01-01

    The rigid γ-globulin matrix (50 mg) as a carrier for drug delivery system was made by γ-ray irradiation after melt-pressing at 75 0 C under a pressure of 100 kg/cm 2 . The in vivo degradation (weight loss) of the matrix when implanted subcutaneously in the back of wistar rats was about 1.9% at 90th day from implantation. When 0.1 M Tartarate buffer solution (pH 1.8) containing 0, 0.005, 0.01 and 0.1 w/v% pepsin was used as a digestive medium (37 0 C), the in vitro degradation (weight loss) of the matrix was 1.2, 31.4, 45.7 and 53.9% at 90th day from start of the test, respectively. Therefore, it was concluded that the in vivo degradation of the matrix was much slower than that in vitro. On the basis of these results, testosterone (15 mg) as a drug was entrapped in γ-globulin matrix irradiated after melt-pressing. The in vivo degradation of matrix itself was significantly accelerated in the presence of drug, and reached up to 57.4% at 90th day from implantation. The in vivo release of drug from the composites was investigated using castrated Wistar rats. Furthermore, the study of the relationship between the in vivo release of drug and the physiological response (change in weight of the ventral prostate) indicated that the efficacious drug release continued up to 60 days. (author)

  15. 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

  16. 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)

  17. 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.

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  19. Correlations between Serum Testosterone, Estradiol, and Sex Hormone-Binding Globulin and Bone Mineral Density in a Diverse Sample of Men

    OpenAIRE

    Araujo, Andre B.; Travison, Thomas G.; Leder, Benjamin Z.; McKinlay, John B.

    2008-01-01

    Context: The relationship between hormones and bone mineral density (BMD) in men has received considerable attention. However, most studies have been conducted in homogenous populations, and it is not known whether differences in hormones impact racial and ethnic differences in BMD.

  20. 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.

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  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. Preferential interaction of β-globulin from sesame seeds (Sesamum indicum L.) with cosolvents is accompanied by the protein structural reorganization.

    Science.gov (United States)

    Sekhar, P M Guna; Yadav, Jay Kant

    2013-05-01

    The effect of a cosolvent on the structure and stability of a protein depends upon the nature of preferential protein- water, protein-cosolvent or cosolvent-water interactions. The preferential interaction parameters of glycerol, sorbitol and sucrose with β-globulin (from Sesamum indicum L. seeds) were evaluated and the results showed the exclusion of cosolvents and preferential hydration of the protein. Data from fluorescence, circular dichroism (CD) and thermal stability measurements inferred that the preferential hydration had a considerable effect on the structure of protein under native conditions. Such cosolvent-protein interactions bring out a previously unnoticed, but outstanding phenomenon of cosolvent induced structural effects on the protein. This study reveals that these cosolvents interact with β-globulin in such a way that they induce a structural reshuffling to enhance the protein stability, mostly by intensifying intra-molecular hydrophobic interactions.

  4. Size at birth, morning cortisol and cardiometabolic risk markers in healthy Indian children.

    Science.gov (United States)

    Krishnaveni, G V; Veena, S R; Dhube, A; Karat, S C; Phillips, D I W; Fall, C H D

    2014-01-01

    Prenatal programming of the hypothalamic-pituitary-adrenal (HPA) axis may link reduced foetal growth with higher adult chronic disease risk. South Asians have a high prevalence of low birth weight and a thin-fat phenotype, which is associated with subsequent type 2 diabetes and the metabolic syndrome. Altered HPA activity could be one of the pathological processes underlying this link. Plasma morning cortisol and corticosteroid-binding globulin (CBG) concentrations were determined in 528 children aged 9·5 years from a prospective birth cohort in India. They had detailed anthropometry at birth, and current measurements of anthropometry, plasma glucose, insulin and lipid concentrations and blood pressure. Insulin resistance (Homeostasis Model Assessment) and insulin secretion (the 30-min insulin increment) were also assessed. None of the birth measurements were associated with cortisol concentrations, but both birth weight (P = 0·03) and length (P = 0·004) were inversely associated with CBG concentrations. Cortisol concentrations were inversely associated with current body mass index (P = 0·02), and positively associated with glucose (fasting: P risk markers in Indian children. Although cortisol concentrations did not appear to be related to birth size, small size at birth was associated with higher CBG levels, and may be one of the processes by which foetal undernutrition affects adult health. The findings suggest a need for dynamic testing of HPA axis activity (such as measuring stress responses). © 2013 John Wiley & Sons Ltd.

  5. 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.

  6. 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

  7. 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.

  8. Immunosuppressive therapy with horse anti-thymocyte globulin and cyclosporine as treatment for fulminant aplastic anemia in children.

    Science.gov (United States)

    Yagasaki, Hiroshi; Shichino, Hiroyuki; Ohara, Akira; Kobayashi, Ryoji; Yabe, Hiromasa; Ohga, Shouichi; Hamamoto, Kazuko; Ohtsuka, Yoshitoshi; Shimada, Hiroyuki; Inoue, Masami; Muramatsu, Hideki; Takahashi, Yoshiyuki; Kojima, Seiji

    2014-05-01

    Patients with severe aplastic anemia (SAA) and an absolute neutrophil count (ANC) of 0 typically have fatal outcomes. We defined fulminant AA (FAA) as ANC = 0 for at least 2 weeks prior to and after immunosuppressive therapy (IST). We analyzed the outcomes of 35 children with FAA among 288 children who enrolled in a prospective study for AA (AA-97 study). AA was classified as FAA (n = 35), very SAA (vSAA; n = 129), or SAA (n = 124). All of the children received the IST with horse anti-thymocyte globulin (ATG) and cyclosporine (CsA). A significantly lower response rate at 6 months was seen in children with FAA when compared to those with vSAA or SAA (40.0, 63.6, and 63.7 %, respectively; p = 0.027). Of 20 nonresponder patients in the FAA group, 11 were rescued by alternative donor transplantation, and 5 patients showed a late response after 6 months. Consequently, no significant difference was noted in overall survival when comparing the FAA, vSAA, and SAA groups (88.5, 95.8, and 96.8 %). These findings indicate that IST with ATG and CsA is justified as a first-line treatment for children with FAA who lack a human leukocyte antigen-matched sibling donor.

  9. 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.

  10. 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

  11. 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 mortality after immunosuppressive therapy with this agent. Hematological response at 6 months was observed in only 29.7% of all patients. OS at 1 year after rabbit ATG was 75.3%; and age > 35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 10 9 /L (OR 2.65, P 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.

  12. 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.

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

    Science.gov (United States)

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

    2014-09-01

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

  14. 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.

  15. The global availability of rabies immune globulin and rabies vaccine in clinics providing direct care to travelers.

    Science.gov (United States)

    Jentes, Emily S; Blanton, Jesse D; Johnson, Katherine J; Petersen, Brett W; Lamias, Mark J; Robertson, Kis; Franka, Richard; Briggs, Deborah; Costa, Peter; Lai, Irene; Quarry, Doug; Rupprecht, Charles E; Marano, Nina; Brunette, Gary W

    2013-01-01

    Rabies, which is globally endemic, poses a risk to international travelers. To improve recommendations for travelers, we assessed the global availability of rabies vaccine (RV) and rabies immune globulin (RIG). We conducted a 20-question online survey, in English, Spanish, and French, distributed via e-mail to travel medicine providers and other clinicians worldwide from February 1 to March 30, 2011. Results were compiled according to the region. Among total respondents, only 190 indicated that they provided traveler postexposure care. Most responses came from North America (38%), Western Europe (19%), Australia and South and West Pacific Islands (11%), East and Southeast Asia (8%), and Southern Africa (6%). Approximately one third of 187 respondents stated that patients presented with wounds from an animal exposure that were seldom or never adequately cleansed. RIG was often or always accessible for 100% (n = 5) of respondents in the Middle East and North Africa; 94% (n = 17) in Australia and South and West Pacific Islands; 20% (n = 1) in Tropical South America; and 56% (n = 5) in Eastern Europe and Northern Asia. Ninety-one percent (n = 158) of all respondents reported that RV was often or always accessible. For all regions, 35% (n = 58) and 26% (n = 43) of respondents felt that the cost was too high for RIG and RV, respectively. The availability of RV and RIG varied by geographic region. All travelers should be informed that RIG and RV might not be readily available at their destination and that travel health and medical evacuation insurance should be considered prior to departure. Travelers should be educated to avoid animal exposures; to clean all animal bites, licks, and scratches thoroughly with soap and water; and to seek medical care immediately, even if overseas. © 2013 International Society of Travel Medicine.

  16. Preoperative albumin/globulin ratio is a potential prognosis predicting biomarker in patients with resectable gastric cancer.

    Science.gov (United States)

    Xue, Fan; Lin, Feng; Yin, Min; Feng, Ning; Zhang, Xu; Cui, You Gang; Yi, Yu Peng; Kong, Xiang Yu; Chen, Xi; Liu, Wen Zhi

    2017-11-01

    To investigate the prognostic significance of preoperative albumin to globulin ratio (AGR) in patients with resectable gastric cancer (GC). According to the inclusion criteria, 269 GC patients (male:female=127:67; median age: 67 years) with a stage I through III who underwent gastrectomy with D2 lymphadenectomy and R0 resection were included. These patients were categorized into two groups, namely low AGR group and high AGR group, based on a cutoff point that was obtained using a receiver-operating characteristic curve. The correlations of preoperative AGR with the clinicopathological characteristics and overall survival were analyzed. Univariate and multivariate analysis were performed to assess the prognostic value of preoperative AGR. Age, gender, tumor size, T stage, and preoperative hemoglobin were significantly different between the low and high AGR groups (ppreoperative hemoglobin were found to be independent risk factors of low preoperative AGR. Kaplan-Meier curves showed a significantly lower overall survival for the low AGR group (13 months; 95% confidence interval (CI), 10.9-15.1) compared to the high AGR group (17 months; 95% CI, 13.8-20.2; p=0.014). The univariate analysis of all the variables showed that overall survival was significantly related to age; tumor size; differentiation degree; T stage; N stage; tumor, node, metastasis (TNM) stage; preoperative AGR; and hemoglobin (ppreoperative AGR (Preoperative AGR was significantly associated with the prognosis of GC patients in our study. In addition, preoperative AGR is suggested to be a simple but efficient prognosis predicting biomarker in patients with GC.

  17. Profiling of Concanavalin A-Binding Glycoproteins in Human Hepatic Stellate Cells Activated with Transforming Growth Factor-β1

    Directory of Open Access Journals (Sweden)

    Yannan Qin

    2014-11-01

    Full Text Available Glycoproteins play important roles in maintaining normal cell functions depending on their glycosylations. Our previous study indicated that the abundance of glycoproteins recognized by concanavalin A (ConA was increased in human hepatic stellate cells (HSCs following activation by transforming growth factor-β1 (TGF-β1; however, little is known about the ConA-binding glycoproteins (CBGs of HSCs. In this study, we employed a targeted glycoproteomics approach using lectin-magnetic particle conjugate-based liquid chromatography-tandem mass spectrometry to compare CBG profiles between LX-2 HSCs with and without activation by TGF-β1, with the aim of discovering novel CBGs and determining their possible roles in activated HSCs. A total of 54 and 77 proteins were identified in the quiescent and activated LX-2 cells, respectively. Of the proteins identified, 14.3% were glycoproteins and 73.3% were novel potential glycoproteins. Molecules involved in protein processing in the endoplasmic reticulum (e.g., calreticulin and calcium signaling (e.g., 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase β-2 [PLCB2] were specifically identified in activated LX-2 cells. Additionally, PLCB2 expression was upregulated in the cytoplasm of the activated LX-2 cells, as well as in the hepatocytes and sinusoidal cells of liver cirrhosis tissues. In conclusion, the results of this study may aid future investigations to find new molecular mechanisms involved in HSC activation and antifibrotic therapeutic targets.

  18. 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 ...

  19. Long-term follow up after allogeneic stem cell transplantation in patients with severe aplastic anemia after cyclophosphamide plus antithymocyte globulin conditioning

    Science.gov (United States)

    Konopacki, Johanna; Porcher, Raphaël; Robin, Marie; Bieri, Sabine; Cayuela, Jean-Michel; Larghero, Jérôme; Xhaard, Aliénor; Andreoli, Anna Lisa; Dhedin, Nathalie; Petropoulou, Anna; Rodriguez-Otero, Paula; Ribaud, Patricia; Moins-Teisserenc, Hélène; Carmagnat, Maryvonnick; Toubert, Antoine; Chalandon, Yves; Socie, Gérard; Peffault de Latour, Régis

    2012-01-01

    Background Due to increased rates of secondary solid organ cancer in patients with severe aplastic anemia who received an irradiation-based conditioning regimen, we decided some years ago to use the combination of cyclophosphamide and antithymocyte globulin. We report the long-term follow up of patients who underwent hematopoietic stem cell transplantation from an HLA-matched sibling donor after this conditioning regimen. Design and Methods We analyzed 61 consecutive patients transplanted from June 1991 to February 2010, following conditioning with cyclophosphamide (200 mg/kg) and antithymocyte globulin (2.5 mg/kg/day × 5 days). Results Median age was 21 years (range 4–43); 41 of the 61 patients were adults. Median duration of the disease before hematopoietic stem cell transplantation was 93 days. All but 2 patients received bone marrow as the source of stem cells and all but 2 engrafted. Cumulative incidence of acute grade II–IV graft-versus-host disease was 23% (95%CI 13–34) and 18 developed chronic graft-versus-host disease (cumulative incidence 32% at 72 months, 95% CI 20–46). In multivariate analysis, a higher number of infused CD3 cells was associated with an increased risk of developing chronic graft-versus-host disease (P=0.017). With a median follow up of 73 months (range 8–233), the estimated 6-year overall survival was 87% (95% CI 78–97). At 72 months, the cumulative incidence of avascular necrosis was 21% and 12 patients presented with endocrine dysfunction (cumulative incidence of 19%). Only one patient developed a secondary malignancy (Hodgkin’s lymphoma) during follow up. Conclusions Cyclophosphamide and antithymocyte globulin is an effective conditioning regimen for patients with severe aplastic anemia and is associated with low treatment-related mortality. Long-term complications include avascular necrosis and endocrine dysfunction. PMID:22180425

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

    Directory of Open Access Journals (Sweden)

    Christopher Dardis

    2015-02-01

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

  1. Long-term outcome of aplastic anemia in adults treated with antithymocyte globulin: comparison with bone marrow transplantation.

    Science.gov (United States)

    Paquette, R L; Tebyani, N; Frane, M; Ireland, P; Ho, W G; Champlin, R E; Nimer, S D

    1995-01-01

    The outcome of 155 adult aplastic anemia (AA) patients treated with antithymocyte globulin (ATG, Upjohn, Kalamazoo, MI) at University of California, Los Angeles from 1977 to 1988 was evaluated. The median survival of the 146 patients who did not undergo bone marrow transplantation was 5.6 years, with 49% +/- 4% surviving more than 6 years. The most important predictor of survival was positive response to ATG (P < 0.001), which was observed in 48% of patients. Among pretreatment variables, disease severity was the best predictor of survival. Patients with moderate AA (MAA) had significantly better survival than those with severe (SAA) or very severe (VSAA) disease (P = 0.04). The 6-year actuarial survival rates of the three groups were 71% +/- 9%, 48% +/- 7% and 38% +/- 7%, respectively. Cox regression analysis found disease severity to be the only pretreatment variable significantly associated with survival (P = .02). Patient age, sex, disease etiology, concurrent treatment with androgens, or duration of ATG therapy were not associated with differences in survival or response to ATG. Late clonal hematologic complications (ie, myelodysplasia, acute myelogenous leukemia) were observed in 5 of the 77 patients followed for more than 2 years after ATG treatment. In addition, one case of non-Hodgkin's lymphoma and three solid tumors occurred in the ATG-treated patients. The survival of 56 ATG-treated patients with SAA or VSAA between the ages of 16 and 43 did not differ significantly from that of 55 adult AA patients who underwent bone marrow transplant (BMT) during the same time period (P = 0.6). However, 6-year survival rates improved from 43% for patients transplanted before 1984, to 72% for those who underwent BMT between 1984 and 1989. In contrast, there was no difference in the survival rates of patients treated with ATG during these two time periods (46% v 45%, respectively). The results suggest a superior long-term outcome for adult patients with SAA treated with

  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. DNS & Bind Cookbook

    CERN Document Server

    Liu, Cricket

    2011-01-01

    The DNS & BIND Cookbook presents solutions to the many problems faced by network administrators responsible for a name server. Following O'Reilly's popular problem-and-solution cookbook format, this title is an indispensable companion to DNS & BIND, 4th Edition, the definitive guide to the critical task of name server administration. The cookbook contains dozens of code recipes showing solutions to everyday problems, ranging from simple questions, like, "How do I get BIND?" to more advanced topics like providing name service for IPv6 addresses. It's full of BIND configuration files that yo

  4. Environmental xenobiotics may disrupt normal endocrine function by interfering with the binding of physiological ligands to steroid receptors and binding proteins.

    Science.gov (United States)

    Danzo, B J

    1997-01-01

    The disruption of the reproductive system of male and female animals in the wild has been attributed to environmental chemicals (xenobiotics). The effects seen mirror alterations one might anticipate if the steroid hormone-dependent processes that regulate these systems were impaired. To determine whether xenobiotics (present at a concentration of 100 microM) exert their action through steroid-mediated pathways, we examined their ability to inhibit the binding of [3H]physiological ligands (present at a concentration of 7 nM) to the androgen and estrogen receptors, rat androgen-binding protein (ABP), and human sex hormone-binding globulin (hSHBG). The gamma- and delta-isomers of hexachlorocyclohexane, congeners of dichlorodiphenyl-trichloroethane (DDT; p,p'-DDT; p,p'-DDE; o,p'-DDT), dieldrin, atrazine, and pentachlorophenol, caused a statistically significant inhibition of specific binding of [3H]5 alpha-DHT to the androgen receptor that ranged from 100% (p,p'-DDE) to 25% (dieldrin). Methoxychlor, o,p'-DDT1, pentachlorophenol, and nonylphenol significantly reduced [3H]17 beta-estradiol binding to the estrogen receptor by 10, 60, 20, and 75%, respectively. The binding of [3H]5 alpha-DHT to ABP was inhibited 70% by the delta-isomer of hexachlorocyclohexane, but the gamma-isomer did not reduce binding significantly. Methoxychlor, p,p'-DDT, atrazine, and nonylphenol reduced [3H]5 alpha-DHT binding to ABP by approximately 40%. Nonylphenol reduced the binding of [3H]5 alpha-DHT to hSHBG by 70%. Hexachlorocyclohexane reduced [3H]5 alpha-DHT binding to hSHBG by 20%, but the stereospecific effects observed with ABP did not occur. o,p'-DDT and pentachlorophenol resulted in a statistically significant 20% inhibition of [3H]5 alpha-DHT binding to hSHBG. Some xenobiotics resulted in dissociation of [3H]ligands from their binding proteins that was statistically identical to that caused by the unlabeled natural ligand, whereas others resulted in slower or more rapid dissociation

  5. 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.

  6. Comparison of Different Rabbit Anti-Thymocyte Globulin Formulations in Allogeneic Stem Cell Transplantation: Systematic Literature Review and Network Meta-Analysis.

    Science.gov (United States)

    Gagelmann, Nico; Ayuk, Francis; Wolschke, Christine; Kröger, Nicolaus

    2017-12-01

    Since 2000, various phase III randomized controlled trials (RCTs) have investigated the efficacy of rabbit antithymocyte globulin (ATG) in patients following allogeneic stem cell transplantation (allo-SCT). Comparisons of different ATG formulations are lacking, however. Our aim was to synthesize all published efficacy evidence to enable a comparison of all available formulations of rabbit ATG in the allo-SCT setting. We performed a systematic literature review to identify all available phase III RCT evidence. We searched the Cochrane Library, MEDLINE, MEDLINE In-Process, and the website www.ClinicalTrials.gov. In addition, a trial presented at the Annual Meeting of the American Society of Hematology 2016 was added to include the most recent evidence. We identified a total of 6 RCTs, including 2 formulations: anti-T lymphocyte globulin (ATLG; Grafalon, Neovii Biotech, Lexington, MA) and polyclonal globulin immunized with human thymocytes (Thymoglobulin [Thymo]; Genzyme-Sanofi, Cambridge, MA). The evidence was synthesized using a conventional network meta-analysis (NMA). The best treatment for preventing graft-versus-host disease (GVHD) was ATLG, which had a more favorable hazard ratio (HR) compared with standard treatment (chronic GVHD: HR, .42; 95% confidence interval [CI], .31 to .56; acute GVHD grade II-IV: HR, .54; 95% CI, .39 to .73; acute GVHD grade III-IV: HR, .50; 95% CI, .29 to .86), whereas both ATLG and Thymo were at least similarly effective in terms of transplantation-related mortality (TRM) (ATLG: HR, .90; 95% CI, .61 to 1.32; Thymo: HR, .90; 95% CI, .56 to 1.44). Thymo tended to be the better treatment option regarding overall survival (OS) (HR, .86; 95% CI, .59 to 1.26). Our NMA provides the first report of the relative efficacy of all available rabbit ATG formulations in patients undergoing allo-SCT. Until additional data from randomized head-to-head comparisons are available, based on the present analysis, ATLG seems to be the best option to

  7. DNS BIND Server Configuration

    Directory of Open Access Journals (Sweden)

    Radu MARSANU

    2011-01-01

    Full Text Available After a brief presentation of the DNS and BIND standard for Unix platforms, the paper presents an application which has a principal objective, the configuring of the DNS BIND 9 server. The general objectives of the application are presented, follow by the description of the details of designing the program.

  8. DNS BIND Server Configuratio

    OpenAIRE

    Radu MARSANU

    2011-01-01

    After a brief presentation of the DNS and BIND standard for Unix platforms, the paper presents an application which has a principal objective, the configuring of the DNS BIND 9 server. The general objectives of the application are presented, follow by the description of the details of designing the program.

  9. DNS BIND Server Configuration

    OpenAIRE

    Radu MARSANU

    2011-01-01

    After a brief presentation of the DNS and BIND standard for Unix platforms, the paper presents an application which has a principal objective, the configuring of the DNS BIND 9 server. The general objectives of the application are presented, follow by the description of the details of designing the program.

  10. Melanin-binding radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  11. 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

  12. 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

  13. 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)

  14. INDUCTION OF PROTEIN DROPLET (ALPHA(2-MU)-GLOBULIN) NEPHROPATHY IN MALE-RATS AFTER SHORT-TERM DOSAGE WITH 1,8-CINEOLE AND L-LIMONENE

    DEFF Research Database (Denmark)

    Kristiansen, E.; Madsen, Charlotte Bernhard

    1995-01-01

    As part of a series of short-term studies on peppermint oil constituents for their possible induction of the encephalopathy found with peppermint oil, 1,8-cineole and l-limonene were studied. Groups of 10 male Wistar rats were given 0, 500, or 1000 mg 1,8-cineole/kg body wt./day or 0, 800, or 1600...... mg l-limonene/kg body wt./day for 2& days. 1,8-Cineole and l-limonene both induced accumulation of protein droplets containing alpha(2 mu)-globulin in proximal tubular epithelial cells in male rats. These results suggest that both 1,8-cineole and I-limonene possibly belong to the group of chemicals...

  15. Chart validation of inpatient ICD-9-CM administrative diagnosis codes for acute myocardial infarction (AMI) among intravenous immune globulin (IGIV) users in the Sentinel Distributed Database.

    Science.gov (United States)

    Ammann, Eric M; Schweizer, Marin L; Robinson, Jennifer G; Eschol, Jayasheel O; Kafa, Rami; Girotra, Saket; Winiecki, Scott K; Fuller, Candace C; Carnahan, Ryan M; Leonard, Charles E; Haskins, Cole; Garcia, Crystal; Chrischilles, Elizabeth A

    2018-02-15

    The Sentinel Distributed Database (SDD) is a large database of patient-level administrative health care records, primarily derived from insurance claims and electronic health records, and is sponsored by the US Food and Drug Administration for medical product safety evaluations. Acute myocardial infarction (AMI) is a common study endpoint for drug safety studies that rely on health records from the SDD and other administrative databases. In this chart validation study, we report on the positive predictive value (PPV) of inpatient International Classification of Diseases, Ninth Revision, Clinical Modification AMI administrative diagnosis codes (410.x1 and 410.x0) in the SDD. As part of an assessment of thromboembolic adverse event risk following treatment with intravenous immune globulin, charts were obtained for 103 potential post-intravenous immune globulin AMI cases. Charts were abstracted by trained nurses and physician-adjudicated based on prespecified diagnostic criteria. Acute myocardial infarction status could be determined for 89 potential cases. The PPVs for the inpatient AMI diagnoses recorded in the SDD were 75% overall (95% CI, 65-84%), 93% (95% CI, 78-99%) for principal-position diagnoses, 88% (95% CI, 72-97%) for secondary diagnoses, and 38% (95% CI, 20-59%) for position-unspecified diagnoses (eg, diagnoses originating from separate physician claims associated with an inpatient stay). Of the confirmed AMI cases, demand ischemia was the suspected etiology more often for those coded in secondary or unspecified positions (72% and 40%, respectively) than for principal-position AMI diagnoses (21%). The PPVs for principal and secondary AMI diagnoses were high and similar to estimates from prior chart validation studies. Position-unspecified diagnosis codes were less likely to represent true AMI cases. Copyright © 2018 John Wiley & Sons, Ltd.

  16. 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....

  17. 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

  18. Identification of Cyclin A Binders with a Fluorescent Peptide Sensor.

    Science.gov (United States)

    Pazos, Elena; Mascareñas, José L; Vázquez, M Eugenio

    2016-01-01

    A peptide sensor that integrates the 4-dimethylaminophthalimide (4-DMAP) fluorophore in a short cyclin A binding sequence displays a large fluorescence emission increase upon interacting with the cyclin A Binding Groove (CBG). Competitive displacement assays of this probe allow the straightforward identification of peptides that interact with the CBG, which could potentially block the recognition of CDK/cyclin A kinase substrates.

  19. 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

  20. 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

  1. binding protein (HABP1)

    Indian Academy of Sciences (India)

    Unknown

    adsorbed on carbon coated copper grid (400 mesh) for. 5 min at room temperature. The grids were subsequently .... and inhibition by GAGs and DMA were determined on polystyrene wells of microtitre plates (Costar, ... for binding inhibition assays was carried out by mixing equal volumes of the conjugate and the inhibitor at ...

  2. Quarkeosynthesis Binding Energy

    Science.gov (United States)

    Webb, Bill

    2009-05-01

    Quarkeosynthesis shows that the binding energy of a nucleus is the difference between the relativistic kinetic energies of its threesome of Jumbo Quarks and that of its building block quarks from neutrons and protons. There is no involvement of a nuclear strong force or gluon material.

  3. 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.

  4. binding protein (HABP1)

    Indian Academy of Sciences (India)

    Unknown

    of HA in a concentration-dependent manner, suggesting its multiligand affinity amongst carbohydrates. rHABP1 shows differential affinity ... site is seen to correspond to the carbohydrate-binding site in E-selectin, which has similarity in the ... adsorbed on carbon coated copper grid (400 mesh) for. 5 min at room temperature.

  5. Enrichment and identification of the most abundant zinc binding proteins in developing barley grains by Zinc-IMAC capture and nano LC-MS/MS

    DEFF Research Database (Denmark)

    Dionisio, Giuseppe; Uddin, Mohammad Nasir; Vincze, Eva

    2018-01-01

    , 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......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...

  6. 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.

  7. Fludarabine, cyclophosphamide and antithymocyte globulin as total body irradiation-free conditioning for matched related and unrelated allogeneic stem cell transplantation in severe aplastic anemia

    Science.gov (United States)

    Anderlini, Paolo; Acholonu, Sandra; Okoroji, Grace-Julia; Bassett, Roland E.; Giralt, Sergio; Shpall, Elizabeth J; Qazilbash, Muzaffar; Popat, Uday; Worth, Laura; Champlin, Richard E.

    2014-01-01

    Twenty severe aplastic anemia (SAA) patients underwent allogeneic stem cell transplantation (allo-SCT) with fludarabine (FLU), cyclophosphamide and antithymocyte globulin from a matched related (n=7, age ≥ 40) or unrelated donor (n=13, any age). Median age was 34 years (range 1–59). Median time from diagnosis to allo-SCT was 12 months (range 2–244). Seventeen out of 19 evaluable patients engrafted (90%). There were two secondary graft failures (10%). Median time to neutrophil recovery was 15 days (range 8–30). Chimerism studies indicated ≥90% donor-derived engraftment in 16/19 evaluable patients (75%). Four out of 20 patients (20%) developed acute (grade II–IV) GVHD, and 6/16 evaluable patients (37%) developed chronic GVHD. We observed EBV reactivation and viremia in seven patients, which was successfully treated with rituximab in all but one instance (where it was self-limiting). Thirteen patients (62%) are alive (including eight of the last nine treated) with a median follow-up of 30 months (range 3–112). Seven patients expired (graft rejection n=1, GVHD n=1, multiorgan failure n=1, infection n=2, EBV post-transplant lymphoproliferative disorder/PTLD n=2). Total body irradiation-free, FLU-based conditioning for matched related and unrelated allo-SCT is feasible with high engraftment rates. EBV PTLD remains a drawback of this approach. PMID:20939697

  8. Low Preoperative albumin-to-globulin ratio Predict Poor Survival and Negatively Correlated with Fibrinogen in Resectable Esophageal Squamous Cell Carcinoma

    Science.gov (United States)

    Li, Xiao-Hui; Gu, Wen-Shen; Wang, Xue-Ping; Lin, Jian-Hua; Zheng, Xin; Zhang, Lin; Kang, Ting; Zhang, Zhi-Xian; Liu, Wan-li

    2017-01-01

    Background: Although various inflammation-based indexes in esophageal carcinoma have been documented, but the prognostic value of the albumin-to-globulin ratio(AGR) and its correlation with fibrinogen in resectable ESCC remain unknown. Methods: The levels of pre-treatment serum common acute phase proteins (including CRP, albumin and fribrinogen) were retrospectively analyzed in 447 patients with ESCC who underwent surgical resection at our department. The prognostic value was explored by univariate and multivariate cox hazard analysis. The correlation between AGR and acute phase proteins were also analyzed. Results: Patients with decreased levels of AGR and increased CRP had significantly lower 5-year survival rates than those with higher AGR, not only in the whole ESCC cohort but also in the subgroups stratified according to the disease T, N classifications, and metastasis, whereas the other acute phase proteins were not independent prognostic factors for ESCC. In addition, a lower AGR level was observed more often in patients with a high fibrinogen level than in those with a low fibrinogen level. Spearman's rank correlation analysis revealed that the AGR level presented a negative correlation with the fibrinogen level (r =-0.317, pacute phase reactants. PMID:28819381

  9. 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.

  10. 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.

  11. 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

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

    Directory of Open Access Journals (Sweden)

    Srinivas Kammanadiminti

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

  13. Immune reconstitution and outcomes after conditioning with anti-thymocyte-globulin in unrelated cord blood transplantation; the good, the bad, and the ugly

    Science.gov (United States)

    de Koning, Coco; Admiraal, Rick; Nierkens, Stefan

    2017-01-01

    Unrelated umbilical cord blood transplantation (UCBT) exhibits a low risk of graft-versus-host-disease (GvHD) and has unique potent anti-virus and anti-leukemia effects. Anti-thymocyte globulin (ATG) in the conditioning regimen for UCBT is successful in reducing graft rejection and GvHD. Nevertheless, this beneficial effect of ATG coincides with its detrimental effect on immune reconstitution. The latter directly relates to a high incidence of viral infections and leukemia relapses. ATG has been used in transplant patients for over 30 years. In recent years, the knowledge on the mechanisms of action of ATG and its implementation in the UCBT setting has increased dramatically. Important data became available showing the highly variable pharmacokinetics (PK) of ATG and its consequence on outcome measures. Here, we review the effects of ATG on immune reconstitution and subsequent outcomes after UCBT, and describe the mechanisms causing these effects. We highlight the importance of optimizing ATG exposure before and after UCBT and discuss strategies to maintain the ‘good’ and overcome the ‘bad and ugly’ effects of ATG on UCBT outcome. PMID:28607912

  14. Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation.

    Science.gov (United States)

    Suehiro, Taketoshi; Shimada, Mitsuo; Kishikawa, Keiji; Shimura, Tatsuo; Soejima, Yuji; Yoshizumi, Tomoharu; Hashimoto, Kohji; Mochida, Yasushi; Maehara, Yoshihiko; Kuwano, Hiroyuki

    2005-12-01

    Hepatic grafts from hepatitis B surface antigen-negative and anti-core antibody (HBcAb)-positive donors have been shown to transmit hepatitis B virus (HBV) infection. Recently, it has been reported that combined hepatitis B immune globulin (HBIG) and lamivudine therapy is effective in the prevention of hepatitis B recurrence after living donor liver transplantation (LDLT). In this report, we assessed the efficacy of combined HBIG and lamivudine therapy in preventing HBV transmission by graft with HBcAb-positive donors. We studied 22 patients who had undergone LDLT with allografts from HBcAb-positive living donors at Gunma University Hospital and Kyushu University Hospital. Long-term combined HBIG and lamivudine therapy were administrated to all recipients. Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody. Liver biopsies from grafts were tested for HBV DNA. All recipients were HBcAb negative before LDLT. All of the donor livers were HBV DNA positive at the time of LDLT. All of the recipients had HBsAb titers greater than 300 mIU/ml 4 weeks after LDLT, and remained 100 mIU/ml thereafter. None of the recipients have become infected with HBV with a follow-up of 25-86 months. Perioperative combined HBIG and lamivudine therapy can prevent HBV infection in recipients who receive liver grafts from HBcAb-positive donors.

  15. Flow cytometry beads rather than the antihuman globulin method should be used to detect HLA Class I IgG antibody (PRA) in cadaveric renal regraft candidates.

    Science.gov (United States)

    Bryan, Christopher F; McDonald, Scott B; Baier, Karen A; Luger, Alan M; Aeder, Mark I; Murillo, Daniel; Muruve, Nicolas A; Nelson, Paul W; Shield, Charles F; Warady, Bradley A

    2002-01-01

    HLA Class I antibody screening can be performed by flow cytometry using a mixture of 30 distinct bead populations each coated with the Class I antigen phenotype derived from different cell lines. In this study we compared the efficacy of Class I antibody screens done by flow cytometry beads with the antihuman globulin (AHG) method for patients awaiting cadaveric renal retransplantation. Class I panel reactive antibody (PRA) screening by flow cytometric beads of 21 regraft serum samples that had all been found to be negative by AHG DTT Class I PRA, revealed that 57.1% (12 of 21) had a flow Class I PRA of > or = 10%. Furthermore, when five regraft sera with an intermediate PRA were screened (mean AHG DTT PRA = 33.2 +/- 13%) the mean flow Class I PRA almost doubled (mean flow PRA = 72.4 +/- 10.2%) (p PRA by flow beads, were divided into the three PRA categories based on their peak flow Class I PRA value (0-20%, 21-79% and > or = 80%), the incidence of a positive flow cross-match was 0%, 72% and 85% and the incidence of retransplantation was 60%, 22% and 10%, in each of these groups, respectively. These data provided our histocompatibility laboratory with the rationale to stop performing the AHG PRA and perform only the flow Class I PRA method for regraft candidates.

  16. 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 (Panemia, 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.

  17. Evaluation of Tc-99m (V DMSA Binding to Human Plasma Proteins

    Directory of Open Access Journals (Sweden)

    Bi-Fang Lee

    2008-01-01

    Full Text Available As a critical step toward elucidating the mechanism of localization of Tc-99m (V dimercaptosuccinic acid (DMSA, we investigated its binding and transport in blood in comparison with Ga-67 citrate. The studies were performed in vitro by incubating Tc-99m (V DMSA with blood (one sample at 4°C and another at 37°C to assess its binding to plasma proteins using ulrrafilrration, dialysis, electrophoresis, gel filtration chromatography and affinity chromatography A parallel experiment for determining the blood binding of Ga-67 citrate was performed using the same procedures. Using ulrrafilrration, dialysis, electrophoresis and gel filtration chromatography, labeled plasma samples showed that protein binding for Tc-99m (V DMSA was 45-54% at 37°C and 73-80% at 4°C. The figures for Ga-67 citrate were 43-53% at 37°C and 75-81% at 4°C. Electrophoresis showed that Tc-99m (V DMSA was mostly bound to plasma albumin (36.05 + 2.48% at 37°C and 60.04 + 1.87% at 4°C, and that the proportion of Ga-67 radioactivity associated with β-globulin was 34.23 + 1.37% at 37°C and 55.71 + 3.69% at 4°C. In affinity chromatography experiments, Tc-99m (V DMSA did not bind to transferrin, unlike Ga-67 citrate. This study demonstrates that, at the radiopharmaceutical tracer level, most Tc-99m (V DMSA in blood is protein-bound, primarily to albumin, but not to transferrin. In contrast, Ga-67 citrate was bound primarily to transferrin. The knowledge that albumin is the main transport protein of Tc-99m (V DMSA may contribute to a better understanding of its biodistribution and pharmacokinetics.

  18. Policies and procedures related to testing for weak D phenotypes and administration of Rh immune globulin: results and recommendations related to supplemental questions in the Comprehensive Transfusion Medicine survey of the College of American Pathologists.

    Science.gov (United States)

    Sandler, S Gerald; Roseff, Susan D; Domen, Ronald E; Shaz, Beth; Gottschall, Jerome L

    2014-05-01

    Advances in RHD genotyping offer an opportunity to update policies and practices for testing weak D phenotypes and administration of Rh immune globulin to postpartum women. To repeat questions from a 1999 College of American Pathologists proficiency test survey, to evaluate current practices for testing for weak D and administration of Rh immune globulin, and to determine whether there is an opportunity to begin integrating RHD genotyping in laboratory practice. The College of American Pathologists Transfusion Medicine Resource Committee sent questions from the 1999 survey to laboratories that participated in the 2012 proficiency test survey. The results of the 2012 survey were compared with those from 1999. Results from published RHD genotyping studies were analyzed to determine if RHD genotyping could improve current policies and practices for serological Rh typing. More than 3100 survey participants responded to the 2012 questions. The most significant finding was a decrease in the number of transfusion services performing a serological weak D test on patients as a strategy to manage those with a weak D as Rh negative (from 58.2% to 19.8%, P policies and practices could improve the accuracy of Rh typing results, reduce unnecessary administration of Rh immune globulin in women with a weak D, and decrease transfusion of Rh-negative red blood cells in most recipients with a serological weak D phenotype.

  19. Coping with pregnancy after 9months in the dark: Post-hibernation buffering of high maternal stress in arctic ground squirrels.

    Science.gov (United States)

    Edwards, Phoebe D; Boonstra, Rudy

    2016-06-01

    Pregnancy and lactation are key times in the life of female mammals when energetic resources must be brought to bear to produce and nurture offspring. Changes in glucocorticoid (GC) levels are central to this objective, due to their roles in modulating development and physiology and in mediating energetic tradeoffs. We examined GC changes over reproduction in a species living in a harsh seasonal environment: the arctic ground squirrel (Urocitellus parryii). Females become pregnant immediately after emerging from a ∼9month hibernation, and then must begin this pregnancy during an additional month of freezing temperatures and limited food availability. We measured plasma levels of total cortisol, corticosteroid-binding globulin (CBG), and free cortisol in unstressed females at three stages: not-visibly pregnant, visibly pregnant, and lactating. Total cortisol levels were similar in all stages, but CBG levels increased 4-fold from the not-visibly pregnant stage to visibly pregnant and lactating stage. As a result, the free cortisol fraction declined from 51% of total cortisol when females were not-visibly pregnant to only 5% when they were visibly pregnant (remaining low and stable throughout pregnancy) and 10% when they were lactating. This pattern is markedly different from that seen in other mammals, where 10% or less of GCs are free and these tend to increase during gestation. We postulate that the high free cortisol just prior to visible pregnancy is a seasonal adaptation relating either to the pronounced physiological changes the female must undergo after emerging from hibernation and immediately getting pregnant, or to the mobilization of body reserves for energy to permit pregnancy, or both. Thereafter, high CBG levels may shield the developing offspring from the negative effects of cortisol overexposure. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan

    2005-01-01

    to express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin-mediated uptake, reveal (125)I-labeled FBP uptake which is inhibited...... to bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin, but not to low density lipoprotein receptor related protein. Binding of (125)I-labeled folate binding protein (FBP) to sections of kidney proximal tubule, known...

  1. Binding matrix: a novel approach for binding site recognition.

    Science.gov (United States)

    Kim, Jan T; Gewehr, Jan E; Martinetz, Thomas

    2004-06-01

    Recognition of protein-DNA binding sites in genomic sequences is a crucial step for discovering biological functions of genomic sequences. Explosive growth in availability of sequence information has resulted in a demand for binding site detection methods with high specificity. The motivation of the work presented here is to address this demand by a systematic approach based on Maximum Likelihood Estimation. A general framework is developed in which a large class of binding site detection methods can be described in a uniform and consistent way. Protein-DNA binding is determined by binding energy, which is an approximately linear function within the space of sequence words. All matrix based binding word detectors can be regarded as different linear classifiers which attempt to estimate the linear separation implied by the binding energy function. The standard approaches of consensus sequences and profile matrices are described using this framework. A maximum likelihood approach for determining this linear separation leads to a novel matrix type, called the binding matrix. The binding matrix is the most specific matrix based classifier which is consistent with the input set of known binding words. It achieves significant improvements in specificity compared to other matrices. This is demonstrated using 95 sets of experimentally determined binding words provided by the TRANSFAC database.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Erkan Demir

    2014-01-01

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

  4. Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen.

    Science.gov (United States)

    Mohty, Mohamad; Bay, Jacques-Olivier; Faucher, Catherine; Choufi, Bachra; Bilger, Karin; Tournilhac, Olivier; Vey, Norbert; Stoppa, Anne-Marie; Coso, Diane; Chabannon, Christian; Viens, Patrice; Maraninchi, Dominique; Blaise, Didier

    2003-07-15

    Reduced-intensity conditioning (RIC) regimens are increasingly used for allogeneic stem cell transplantation (allo-SCT). RIC has been shown to allow engraftment with minimal early transplantation-related mortality (TRM). However, in the context of RIC, predictive factors for acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) and their effect on outcome remain unknown. In this report, we analyzed the outcome of 101 high-risk patients (70 hematologic and 31 nonhematologic malignancies) who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan, and antithymocyte globulin (ATG). The cumulative incidence of grade II-IV aGVHD was 36% (95% confidence interval [CI], 27%-45%), whereas the cumulative incidence of cGVHD at 2 years was 43% (95% CI, 33%-53%). In multivariate analysis, the incidence of aGVHD was significantly associated with the ATG dose infused during conditioning (P =.0005), whereas peripheral blood as stem cell source was the only predictive factor for the development of cGVHD (P =.0007). The 1-year cumulative incidences of disease progression or relapse in patients with (n = 69) and without (n = 31) GVHD (whatever its form or grade) were 30% (95% CI, 19%-41%) and 55% (95% CI, 37%-72%), respectively (P =.02), suggesting that a potent graft-versus-tumor (GVT) effect can be achieved in high-risk patients following RIC. Moreover, the GVT effect was closely associated with GVHD without an increased risk of TRM (cumulative incidence of TRM, 18% [95% CI, 10%-25%]). Collectively, these results provide a framework for the refinement of RIC approaches designed to enhance the GVT effect with an acceptable risk of GVHD.

  5. Elevated myeloid: plasmacytoid dendritic cell ratio associates with late, but not early liver rejection in children induced with, anti-human thymocyte globulin1

    Science.gov (United States)

    Gupta, Ankit; AshokKumar, Chethan; Ningappa, Mylarappa; Sun, Qing; Higgs, Brandon W; Snyder, Sara; Zeevi, Adriana; Thomson, Angus W; Mazariegos, George V; Sindhi, Rakesh

    2009-01-01

    Background Dendritic cells (DC) play an important role in the induction and regulation of immune responses. Methods Myeloid CD11c+DC (MDC), which may have inflammatory functions, and plasmacytoid CD123+ DC (PDC), which may have tolerogenic potential, were measured by flow cytometric analysis, cross-sectionally, once, in 48 children, and longitudinally (pre-transplant, and at days 1–60, 61–200, 201–400 post transplant) in 30 children following liver transplantation (LTx). All children received 53/25 cadaveric/live donor liver allografts with rabbit anti-human thymocyte globulin (rATG) induction, and steroid-free Tacrolimus therapy. Rejectors in both groups were those children (n=35), who experienced biopsy-proven acute cellular rejection (ACR) within 60 days of DC monitoring. Results Among rejectors in the longitudinal and cross-sectional cohorts, the MDC: PDC ratio was higher, and was associated with decreased PDC frequencies. Logistic regression analysis, leave-one out cross-validation, and receiver operating characteristic analysis applied to 30 cross-sectional subjects revealed that an MDC:PDC ratio 1.78 was associated with rejector status with sensitivity/specificity of 76.9/88.2%. Sensitivity and specificity were replicated in the 18 remaining cross-sectional subjects (88.8 and 78.8%, respectively), but not in longitudinally-monitored subjects, during the early, 60-day period after LTx (30.76 and 62.50%, respectively). A significant negative correlation was observed between Tacrolimus whole blood concentrations and PDC frequencies (Spearman r = −0.370, p=0.005) in 48 cross-sectional subjects in whom DC subsets were monitored 1–3 years after LTx, but not during the early post-LTx period. Conclusion We conclude that an elevated MDC: PDC ratio associates with liver graft rejection, which occurs after first year in children induced with rATG. PMID:19696644

  6. 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 measles in bivariate analysis (p=0.0217). Among 8 tested contacts of 17 considered IM ISG PEP failures, post-IM ISG PEP measles IgG antibody levels (mean 16.3days (range 16-17days) post-PEP) were all 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Níveis séricos de globulinas e a intensidade da fibrose hepática em pacientes com esquistossomose mansônica Serum globulin levels and intensity of hepatic fibrosis in patients with mansonic schistosomiasis

    Directory of Open Access Journals (Sweden)

    Henrique S. T. Correia

    2009-09-01

    Full Text Available CONTEXTO: Tem sido descrita correlação entre os níveis séricos de globulinas e o grau de fibrose hepática nas hepatites crônicas, mas não se encontram relatos na esquistossomose mansônica. OBJETIVO: Avaliar os níveis séricos de globulinas e de IgG, e a intensidade da fibrose periportal mensurada pela ultrassonografia em pacientes com esquistossomose mansônica. MÉTODOS: Entre novembro de 2006 e fevereiro de 2007, foram estudados 41 pacientes que preencheram ficha clínica e realizaram dosagens de IgG por imunoturbidimetria e de globulinas indiretamente pelo método do biureto. A ultrassonografia foi realizada por um único pesquisador, seguindo os protocolos do Cairo e de Niamey. RESULTADOS: A média de idade foi 41 anos, sendo 25 pacientes (61% do sexo feminino. Dez dos 41 pacientes (24% apresentaram elevação dos níveis séricos de globulinas e 21 (51% dos de IgG. Conforme a classificação do Cairo, 21 pacientes apresentaram grau I de fibrose, 18 grau II e 2 grau III, e pela classificação de Niamey 8 apresentavam padrão C, 20 D e 13 E. Aqueles com graus II ou III de fibrose tiveram maiores níveis de IgG do que os de grau I (P = 0,047, assim como aqueles que apresentaram padrões D e E em relação ao C (P = 0,011. Não houve associação entre os níveis de globulinas e o grau ou padrão de fibrose. CONCLUSÃO: Em pacientes com esquistossomose mansônica, observou-se elevação dos níveis séricos de IgG de acordo com a progressão do grau e do padrão de fibrose periportal, mas o mesmo não se observou com os níveis de globulinas.BACKGROUND: A correlation between the levels of serum globulins and the hepatic fibrosis degree in chronic hepatitis was described, but reports in schistosomiasis mansoni have not been found. OBJECTIVE: To evaluate the serum globulins and IgG levels, and periportal fibrosis intensity measured by ultrasound in patients with schistosomiasis mansoni. METHODS: Between November, 2006 and February 2007

  12. Glucose-to-insulin ratio rather than sex hormone-binding globulin and adiponectin levels is the best predictor of insulin resistance in nonobese women with polycystic ovary syndrome.

    Science.gov (United States)

    Ducluzeau, Pierre-Henri; Cousin, Patrice; Malvoisin, Etienne; Bornet, Hubert; Vidal, Hubert; Laville, Martine; Pugeat, Michel

    2003-08-01

    Polycystic ovary syndrome (PCOS), the main androgen disorder in women, has been suggested to be associated with a high risk of developing cardiovascular disease and type 2 diabetes. In many PCOS patients, overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance, and has been identified as a target for new therapeutic strategy, including early change in lifestyle. Early biochemical marker(s) for identifying at-risk patients will be useful for prevention studies. The main goal of the present study was to search for such tool(s). We investigated 16 nonobese PCOS women by performing euglycemic hyperinsulinemic clamp and measuring insulin levels during fasting and oral glucose tolerance test, as well as the serum concentrations of SHBG, leptin, and adiponectin, the newly identified adipose factors. Eight of the 16 patients had a steady-state glucose disposal rate less than 8.5 mg/kg.min, the lowest normal value for nonobese control women. These insulin-resistant patients had significant higher body mass index (BMI) and waist-to-hip ratio (WHR), and lower high-density lipoprotein cholesterol and SHBG levels. As expected, glucose disposal correlated negatively with BMI (P = 0.01), WHR (P = 0.01), and fasting insulin level (P = 0.003). On stepwise regression analysis, however, the glucose-to-insulin ratio (GIR) emerged as the strongest independent parameter to appraise insulin resistance (R(2) = 0.61). SHBG level correlated positively with GIR (P < 0.001) and negatively with BMI (P = 0.003) but did not correlate with either insulin response during the glucose tolerance test or plasma leptin and/or adiponectin levels. In contrast, BMI was the only independent predictive parameter of SHBG (P = 0.003, R(2) = 0.73). Interestingly, plasma adiponectin levels were positively associated with glucose disposal rate (P = 0.043) and negatively with WHR (P = 0.024), waist circumference being the best predictor of adiponectin level (P < 0.01). Leptin level correlated only with BMI (r = 0.62, P = 0.01). This study confirmed that insulin resistance, despite the lack of obesity as such, is clearly present in many PCOS women, and demonstrated that GIR is the best predictor for insulin resistance. It was also shown that adiponectin level is a good indicator of abdominal fat mass and is associated to insulin resistance. Finally, low SHBG levels in PCOS are intimately associated with BMI, suggesting that some signal(s) from the adipose tissue, independent of adiponectin and leptin, may regulate liver production of SHBG.

  13. 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...... before blood sampling, but not to the length of daylight or the hours of sunshine. In conclusion, our data showed that day to day levels of inhibin B are relatively constant in men and do not seem to be influenced by seasonal factors. In contrast, we found a seasonal variation in LH and testosterone...

  14. 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......, and SHBG were measured. The intraindividual variation in inhibin B over the study period was, on the average, 10%, corresponding to the assay variation of the inhibin B assay, indicating that most of the observed day to day variation in inhibin B levels in men could be explained by assay variation...... before blood sampling, but not to the length of daylight or the hours of sunshine. In conclusion, our data showed that day to day levels of inhibin B are relatively constant in men and do not seem to be influenced by seasonal factors. In contrast, we found a seasonal variation in LH and testosterone...

  15. HLA-C KIR-Ligands Determine the Impact of Anti-Thymocyte Globulin (ATG) on Graft versus Host and Graft versus Leukemia Effects Following Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Clausen, Johannes; B?hm, Alexandra; Stra?l, Irene; Stiefel, Olga; Buxhofer-Ausch, Veronika; Machherndl-Spandl, Sigrid; K?nig, Josef; Schmidt, Stefan; Steitzer, Hansj?rg; Danzer, Martin; Kasparu, Hedwig; Weltermann, Ansgar; Nachbaur, David

    2017-01-01

    Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk ...

  16. Purification of the S-adenosylmethionine: protein-carboxyl-O-methyltransferase (protein methylase II, E.C. 2.1.1.24). Application to marking with tritium of a bovine gamma globulin

    International Nuclear Information System (INIS)

    Biton, Jacques

    1981-02-01

    This trainee-ship report addresses the isolation and the kinetic study of the carboxy-methyltransferase (methylase II) which can be used to mark a gamma globulin. The objective has also been to extrapolate the first results for various peptidic substrates of biological interest. The author first presents the used materials, the biochemical methods (enzymatic activity measurement, protein dosing), and the physical-chemical methods (ultrafiltration on membrane, counting in liquid scintillation, high performance liquid chromatography, affinity chromatography). Results are then presented and discussed regarding the enzymatic purification by affinity chromatography, and the study of the enzyme in solution (influence of different reaction parameters, definition of the final protocol) [fr

  17. 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

  18. Anti-thymocyte globulin facilitates alloreactive T-cell apoptosis via caspase-3: potential implications for monitoring rejection-free outcomes

    Science.gov (United States)

    Ashokkumar, Chethan; Sun, Qing; Ningappa, Mylarappa; Higgs, Brandon W.; Mazariegos, George; Zeevi, Adriana; Sindhi, Rakesh

    2014-01-01

    Background Alloreactive T-cell apoptosis may explain reduced immunosuppression requirements with pro-apoptotic immunosuppression and among rejection-free recipients. This possibility remains unproven. Methods Apoptotic (caspase-3+, cathepsin-B+) and inflammatory (CD154+) T-cell subsets were evaluated before and after adding rabbit anti-thymocyte globulin (rATG) to mixed lymphocyte co-cultures (MLC) between HLA-mismatched peripheral blood lymphocytes (PBL) from healthy adults. In random samples from children with liver (LTx-20) and intestine (ITx-13) transplantation, apoptotic T-cells were evaluated for association with rejection-free outcomes using the caspase-3 substrate, phiphilux. Results In MLC between normal human PBL, 1) frequencies of memory (M) and naïve (N) Th and Tc, which expressed activated caspase-3, were enhanced most by the combination of allostimulation and rATG, than either stimulus alone. These findings were confirmed with antibody to activated caspase-3, phiphilux, and TUNEL assay, 2) frequencies of Th subsets, which expressed activated cathepsin-B, were similarly increased with combined stimulation. Tc appeared resistant to cathepsin-B activation. 3) with increasing rATG concentrations, proportionately more allospecific CD154+TcM survived than TcM, resulting in relative enrichment of allospecific CD154+TcM. In random blood samples, phiphilux+T-cell subset frequencies were higher among 14 rejection-free LTx and ITx recipients, and demonstrated a greater increase with ex-vivo rATG pre-treatment, than 19 rejectors. In logistic regression analysis, phiphilux+TcM associated best with rejection-free outcomes with sensitivity/specificity of 57%/89%, respectively. Conclusions rATG facilitates apoptosis of alloreactive T-cells via caspase-3 activation, which may explain its steroid-sparing effect in pediatric liver and intestine recipients. Apoptotic susceptibility of T-cytotoxic memory cells, which resist cathepsin-B activation, may distinguish

  19. 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...

  20. 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

  1. Metal binding by food components

    DEFF Research Database (Denmark)

    Tang, Ning

    For calcium binding: Electrochemical method (calcium ion selective electrode) combined with quantum mechanical calculations (density functional theory) were used to investigate the calcium binding affinity of the amino acids and small glycine peptides. The effects of the ionic strength and p......, synergistic effect in calcium binding was found for the small glycine peptide rather than amino acids mixtures with the enhanced driving force up to -6 kJ/mol. Such study provides useful information for the future development of calcium supplements. For zinc binding: Isothermal titration calorimetry...... 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...

  2. Vitamin A status regulates glucocorticoid availability in Wistar rats: consequences on cognitive functions and hippocampal neurogenesis ?

    Directory of Open Access Journals (Sweden)

    Damien eBonhomme

    2014-02-01

    Full Text Available A disruption of the vitamin A signaling pathway has been involved in age-related memory decline and hippocampal plasticity alterations. Using vitamin A deficiency (VAD, a nutritional model leading to a hyposignaling of the retinoid pathway, we have recently demonstrated that retinoic acid (RA, the active metabolite of vitamin A, is efficient to reverse VAD-induced spatial memory deficits and adult hippocampal neurogenesis alterations. Besides, excess of glucocorticoids (GCs occurring with aging is known to strongly inhibit hippocampal plasticity and functions and few studies report on the counteracting effects of RA signaling pathway on GCs action. Here, we have addressed whether the modulation of brain GCs availability could be one of the biological mechanisms involved in the effects of vitamin A status on hippocampal plasticity and functions. Thus, we have studied the effects of a vitamin A-free diet for 14 weeks and a 4-week vitamin A supplementation on plasma and hippocampal corticosterone (CORT levels in Wistar rats. We have also investigated corticosteroid binding globulin (CBG binding capacity and 11beta-Hydrosteroid Dehydrogenase type 1 (11β-HSD1 activity, both important modulators of CORT availability at the peripheral and hippocampal levels respectively. Interestingly, we show that the vitamin A status regulates levels of free plasma CORT and hippocampal CORT levels, by acting through a regulation of CBG binding capacity and 11β-HSD1 activity. Moreover, our results suggest that increased CORT levels in VAD rats could have some deleterious consequences on spatial memory, anxiety-like behavior and adult hippocampal neurogenesis whereas these effects could be corrected by a vitamin A supplementation. Thus, the modulation of GCs availability by vitamin A status is an important biological mechanism that should be taken into account in order to prevent age-related cognitive decline and hippocampal plasticity alterations.

  3. Vitamin A status regulates glucocorticoid availability in Wistar rats: consequences on cognitive functions and hippocampal neurogenesis?

    Science.gov (United States)

    Bonhomme, Damien; Minni, Amandine M; Alfos, Serge; Roux, Pascale; Richard, Emmanuel; Higueret, Paul; Moisan, Marie-Pierre; Pallet, Véronique; Touyarot, Katia

    2014-01-01

    A disruption of the vitamin A signaling pathway has been involved in age-related memory decline and hippocampal plasticity alterations. Using vitamin A deficiency (VAD), a nutritional model leading to a hyposignaling of the retinoid pathway, we have recently demonstrated that retinoic acid (RA), the active metabolite of vitamin A, is efficient to reverse VAD-induced spatial memory deficits and adult hippocampal neurogenesis alterations. Besides, excess of glucocorticoids (GCs) occurring with aging is known to strongly inhibit hippocampal plasticity and functions and few studies report on the counteracting effects of RA signaling pathway on GCs action. Here, we have addressed whether the modulation of brain GCs availability could be one of the biological mechanisms involved in the effects of vitamin A status on hippocampal plasticity and functions. Thus, we have studied the effects of a vitamin A-free diet for 14 weeks and a 4-week vitamin A supplementation on plasma and hippocampal corticosterone (CORT) levels in Wistar rats. We have also investigated corticosteroid binding globulin (CBG) binding capacity and 11beta-Hydrosteroid Dehydrogenase type 1 (11β-HSD1) activity, both important modulators of CORT availability at the peripheral and hippocampal levels respectively. Interestingly, we show that the vitamin A status regulates levels of free plasma CORT and hippocampal CORT levels, by acting through a regulation of CBG binding capacity and 11β-HSD1 activity. Moreover, our results suggest that increased CORT levels in VAD rats could have some deleterious consequences on spatial memory, anxiety-like behavior and adult hippocampal neurogenesis whereas these effects could be corrected by a vitamin A supplementation. Thus, the modulation of GCs availability by vitamin A status is an important biological mechanism that should be taken into account in order to prevent age-related cognitive decline and hippocampal plasticity alterations.

  4. Pro DNS and BIND 10

    CERN Document Server

    Aitchison, Ron

    2011-01-01

    Pro DNS and BIND 10 guides you through the challenging array of features surrounding DNS with a special focus on the latest release of BIND, the world's most popular DNS implementation. This book unravels the mysteries of DNS, offering insight into origins, evolution, and key concepts like domain names and zone files. This book focuses on running DNS systems based on BIND 10, the first stable release that includes support for the latest DNSSEC standards. Whether you administer a DNS system, are thinking about running one, or you simply want to understand the DNS system, then this book for you.

  5. 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

  6. 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

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

    Science.gov (United States)

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

    2017-04-01

    Determining how nanomaterials interact with plasma will assist in understanding their effects on the biological system. This work presents a systematic study of the protein corona formed from human plasma on 20nm silver and gold nanoparticles with three different surface modifications, including positive and negative surface charges. The results show that all nanoparticles, even those with positive surface modifications, acquire negative charges after interacting with plasma. Approximately 300 proteins are identified on the coronas, while 99 are commonly found on each nanomaterial. The 20 most abundant proteins account for over 80% of the total proteins abundance. Remarkably, the surface charge and core of the nanoparticles, as well as the isoelectric point of the plasma proteins, are found to play significant roles in determining the nanoparticle coronas. Albumin and globulins are present at levels of less than 2% on these nanoparticle coronas. Fibrinogen, which presents in the plasma but not in the serum, preferably binds to negatively charged gold nanoparticles. These observations demonstrate the specific plasma protein binding pattern of silver and gold nanoparticles, as well as the importance of the surface charge and core in determining the protein corona compositions. The potential downstream biological impacts of the corona proteins were also investigated. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Asymmetric cation-binding catalysis

    DEFF Research Database (Denmark)

    Oliveira, Maria Teresa; Lee, Jiwoong

    2017-01-01

    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...... and KCN, are selectively bound to the catalyst, providing exceptionally high enantioselectivities for kinetic resolutions, elimination reactions (fluoride base), and Strecker synthesis (cyanide nucleophile). Asymmetric cation-binding catalysis was recently expanded to silicon-based reagents, enabling...

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

    Directory of Open Access Journals (Sweden)

    Nobuyoshi Hanaoka

    2015-09-01

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

  10. Water binding in legume seeds

    Science.gov (United States)

    Vertucci, C. W.; Leopold, A. C.

    1987-01-01

    The physical status of water in seeds has a pivotal role in determining the physiological reactions that can take place in the dry state. Using water sorption isotherms from cotyledon and axis tissue of five leguminous seeds, the strength of water binding and the numbers of binding sites have been estimated using van't Hoff analyses and the D'Arcy/Watt equation. These parameters of water sorption are calculated for each of the three regions of water binding and for a range of temperatures. Water sorption characteristics are reflective of the chemical composition of the biological materials as well as the temperature at which hydration takes place. Changes in the sorption characteristics with temperature and hydration level may suggest hydration-induced structural changes in cellular components.

  11. 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.

  12. 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

  13. Gene regulation by steroid hormones III

    Energy Technology Data Exchange (ETDEWEB)

    Roy, A.K.; Clark, J.H.

    1987-01-01

    In this book, the authors discuss the latest advances in molecular endocrinology: - steroid receptor binding to DNA sequences of hormonally controlled genes, - structure of genes controlled by steroid hormones, - heterogeneity of steroid receptors, - immunochemical approaches to receptor studies, and - the most recent approaches to steroid hormone action and biological response. The Contents discussed are: Biochemical Evidence for the Exclusive Nuclear Localization of the Estrogen Receptor. - Structure, Dynamics, and Cloning of the Estrogen Receptor. - Structure, Dynamics, and Cloning of the Estrogen Receptor - Physical and Functional Parameters of Isolated Estrogen Receptor - Type II Binding Sites: Cellular Origin and an Endogeneous Ligand. - The Two Phosphorylation Reactions of the Progesterone Receptor. - Receptor Mediated Action of the Vitamin D Hormone. - Characterization of the Nuclear Binding Sites (Acceptor Sites) for a Steroid Receptor. Antibodies in Estrogen, Progesterone, Glucocorticoid, Vitamin D Receptors and Autoantibodies to Antrogene Receptor. - Isolation and Characterization of cDNA probes for Human CBG and Rat ABP. Ornithine Decarboxy lase mRNAs in Murine Kidney: Structure and Regulation by Androgens - Glucocorticoid Receptors and the Control of Gene Expression. - Activation and Regulation of the Vitellogenin Gene Family. - Intra- and Intercellular Aspects of the Hormonal Regulation of the ..cap alpha..2..mu.. Globulin Gene Expression. - Hormonal Regulation of Sexually Differentiated Isozymes of Cytochrome P-450 in Rat Liver. - Interaction of Thyroid Hormone and Carbohydrates on Hepatic Gene Expression.

  14. 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)

  15. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

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

    2012-01-01

    The postsynaptic density protein-95/disks large/zonula occludens-1 (PDZ) protein domain family is one of the most common protein-protein interaction modules in mammalian cells, with paralogs present in several hundred human proteins. PDZ domains are found in most cell types, but neuronal proteins...... 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....

  16. Binding energy of protonium ions

    Science.gov (United States)

    Assad Abdel-Raouf, Mohamed

    2009-11-01

    The goal of the present work is to calculate the binding energy of the protonium ions bar PPe+ and bar PPe- using Rayleigh- Ritz variational method. It is indicated that an employment of 21 components of the trial wavefunction yields -0.08793 eV as the ground state energy of these ions. Our result agrees quite well with recently obtained results based on elaborate Monte Carlo approximations. It confirms the possible formation of these ions in laboratory.

  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. Timing of fledging is influenced by glucocorticoid physiology in Laysan Albatross chicks.

    Science.gov (United States)

    Sprague, R S; Breuner, C W

    2010-07-01

    Fledging is a major life transition for birds, when juveniles move from the safety of a nest into an environment where they must find food and avoid predators. The timing of fledging within a season can have significant effects on future survival and breeding success. Proximate triggers of fledging are unknown: though wing development is likely a primary factor, other physiological changes, such as elevated plasma corticosterone (CORT), may affect fledging behavior. Laysan Albatross (Phoebastria immutabilis) chicks have an extended post-hatching period during which they reach 150% of adult mass. However, approaching fledging, chicks fast for days to weeks and lose mass while still putting energy into feather growth. We evaluated chick morphology and physiology to elucidate proximate triggers of fledging. As in some other species, CORT increased as chicks fasted and lost body mass. At the same time, corticosteroid binding globulin (CBG) declined, thus amplifying free CORT prior to fledging. Once chicks reached a morphological threshold, free CORT levels predicted how long they stayed at the colony: chicks with higher free CORT fledged sooner. To perturb the relationship between body condition, endocrine physiology, and fledging behavior, we supplementally fed chicks for the month before fledging. Fed birds had a slower decrease in body mass, slower decrease in CBG, slower increase in free CORT, and stayed at the colony longer after reaching a morphological threshold. Our study suggests that as chicks lose mass, free CORT acts as a signal of energetic or nutritional state to adjust the timing of fledging. Copyright 2010 Elsevier Inc. All rights reserved.

  2. 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

  3. Lactoferrin binding molecules in human seminal plasma.

    Science.gov (United States)

    Thaler, C J; Vanderpuye, O A; McIntyre, J A; Faulk, W P

    1990-10-01

    During ejaculation, the iron binding protein lactoferrin binds to sperm and forms a major component of sperm-coating antigens. Physicochemical properties of lactoferrin in seminal plasma (SP) and on sperm differ from those of purified lactoferrin. These differences have been attributed to the binding of unknown seminal macromolecules to lactoferrin. We have studied lactoferrin binding molecules in SP. The SP samples were coated onto microtiter plates and tested for binding of biotinylated lactoferrin. SP was found to specifically bind biotinylated lactoferrin. This binding was competitively inhibited by coincubation with unlabeled lactoferrin but was not affected by control incubations done with human IgG or transferrin. Lactoferrin binding molecules in SP were biochemically characterized by using SDS-PAGE and ligand blotting. Biotinylated lactoferrin bound to SP molecules of approximately 120, 60 and 30 kDa. No binding was observed with biotinylated transferrin. The presence of molecules that associate with lactoferrin in SP was further studied by using crossed immunoelectrophoresis. Lactoferrin in SP immunoprecipitated as two peaks, one of which corresponded to purified lactoferrin. These results suggest that some lactoferrin molecules in SP are free and that others are associated with lactoferrin binding molecules. Binding of lactoferrin to lactoferrin binding molecules appears to change its physicochemical properties and thus could influence its biologic activity and its affinity to sperm.

  4. Acyl-coenzyme A binding protein (ACBP)

    DEFF Research Database (Denmark)

    Kragelund, B B; Knudsen, J; Poulsen, F M

    1999-01-01

    Acyl-coenzyme A binding proteins are known from a large group of eukaryote species and to bind a long chain length acyl-CoA ester with very high affinity. Detailed biochemical mapping of ligand binding properties has been obtained as well as in-depth structural studies on the bovine apo-protein a...

  5. Fludarabine, cyclophosphamide and horse antithymocyte globulin conditioning regimen for allogeneic peripheral blood stem cell transplantation performed in non-HEPA filter rooms for multiply transfused patients with severe aplastic anemia.

    Science.gov (United States)

    Kumar, R; Prem, S; Mahapatra, M; Seth, T; Chowdhary, D R; Mishra, P; Pillai, L; Narendra, A M V R; Mehra, N K; Saxena, R; Choudhry, V P

    2006-04-01

    Multiply transfused patients of severe aplastic anemia are at increased risk of graft rejection. Five such patients underwent peripheral blood stem cell transplantation from HLA-identical siblings with a fludarabine-based protocol. The conditioning consisted of fludarabine 30 mg/m(2)/day x 6 days, cyclophosphamide 60 mg/kg/day x 2 days and horse antithymocyte globulin (ATG) x 4 days. Two different ATG preparations were used: ATGAM (dose 30 mg/kg/day x 4 days) or Thymogam (dose 40 mg/kg/day x 4 days). Engraftment: median time to absolute neutrophil count (ANC) >0.5 x 10(9)/l was 11 days (range: 8-17) and median time to platelet count >20 x 10(9)/l was 11 days (range: 9-17). At a median follow-up of 171 days (range: 47-389), there has been no graft rejection and all patients are in complete remission. Acute GVHD (grade 1) occurred in one patient only. Chronic GVHD developed in two patients (extensive in one and limited in another). The transplants were performed in non-HEPA filter rooms. In only one patient, systemic antifungal therapy (voriconazole) was used. The use of Thymogam brand of ATG for conditioning is being reported for the first time. Our experience suggests that this fludarabine-based protocol allows rapid sustained engraftment in high-risk patients without significant immediate toxicity.

  6. Chart validation of inpatient International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) administrative diagnosis codes for venous thromboembolism (VTE) among intravenous immune globulin (IGIV) users in the Sentinel Distributed Database.

    Science.gov (United States)

    Ammann, Eric M; Cuker, Adam; Carnahan, Ryan M; Perepu, Usha S; Winiecki, Scott K; Schweizer, Marin L; Leonard, Charles E; Fuller, Candace C; Garcia, Crystal; Haskins, Cole; Chrischilles, Elizabeth A

    2018-02-01

    The Sentinel Distributed Database (SDD) is a database of patient administrative healthcare records, derived from insurance claims and electronic health records, sponsored by the US Food and Drug Administration for evaluation of medical product outcomes. There is limited information on the validity of diagnosis codes for acute venous thromboembolism (VTE) in the SDD and administrative healthcare data more generally.In this chart validation study, we report on the positive predictive value (PPV) of inpatient administrative diagnosis codes for acute VTE-pulmonary embolism (PE) or lower-extremity or site-unspecified deep vein thrombosis (DVT)-within the SDD. As part of an assessment of thromboembolic adverse event risk following treatment with intravenous immune globulin (IGIV), charts were obtained for 75 potential VTE cases, abstracted, and physician-adjudicated.VTE status was determined for 62 potential cases. PPVs for lower-extremity DVT and/or PE were 90% (95% CI: 73-98%) for principal-position diagnoses, 80% (95% CI: 28-99%) for secondary diagnoses, and 26% (95% CI: 11-46%) for position-unspecified diagnoses (originating from physician claims associated with an inpatient stay). Average symptom onset was 1.5 days prior to hospital admission (range: 19 days prior to 4 days after admission).PPVs for principal and secondary VTE discharge diagnoses were similar to prior study estimates. Position-unspecified diagnoses were less likely to represent true acute VTE cases.

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

    Science.gov (United States)

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

    1994-10-01

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

  8. Drug binding properties of neonatal albumin

    DEFF Research Database (Denmark)

    Brodersen, R; Honoré, B

    1989-01-01

    Neonatal and adult albumin was isolated by gel chromatography on Sephacryl S-300, from adult and umbilical cord serum, respectively. Binding of monoacetyl-diamino-diphenyl sulfone, warfarin, sulfamethizole, and diazepam was studied by means of equilibrium dialysis and the binding data were analyzed...... by the method of several acceptable fitted curves. It was found that the binding affinity to neonatal albumin is less than to adult albumin for monoacetyl-diamino-diphenyl sulfone and warfarin. Sulfamethizole binding to the neonatal protein is similarly reduced when more than one molecule of the drug is bound...... per albumin molecule, and binding of the first sulfamethizole molecule is possibly reduced as well. Diazepam binds with equal affinity to the fetal and adult proteins. Among the two main albumin drug-binding functions, for warfarin and diazepam, the former is thus compromised in the newborn infant...

  9. 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

  10. Insulin binding to individual rat skeletal muscles

    Energy Technology Data Exchange (ETDEWEB)

    Koerker, D.J.; Sweet, I.R.; Baskin, D.G. (Univ. of Washington, Seattle (USA))

    1990-10-01

    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.

  11. 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...... diffract X-rays to at least 2.0 A resolution. A complete diffraction data set has been collected to 2.7 A resolution. The crystals of TN, obtained by the vapour-diffusion reverse salting-in method at 280 K, are rhombohedral, space group R3, with the hexagonal axes a = b = 89.1, c = 75.8 A, and diffract...

  12. Binding characteristics of swine erythrocyte insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Dieberg, G.; Bryan, G.S.; Sartin, J.L.; Williams, J.C.; Prince, T.J.; Kemppainen, R.J.

    1985-09-01

    Crossbred gilts had 8.8 +/- 1.1% maximum binding of ( SVI)insulin to insulin receptors on erythrocytes. The number of insulin-binding sites per cell was 137 +/- 19, with a binding affinity ranging from 7.4 X 10(7)M-1 to 11.2 X 10(7)M-1 and mean of 8.8 X 10(7)M-1. Pregnant sows had a significant increase in maximum binding due to an increase in number of receptor sites per cell. Lactating sows fed a high-fiber diet and a low-fiber diet did not develop a significant difference in maximum binding of insulin. Sows fed the low-fiber diet had a significantly higher number of binding sites and a significantly lower binding affinity than did sows fed a high-fiber diet. Receptor-binding affinity was lower in the low-fiber diet group than in cycling gilts, whereas data from sows fed the high-fiber diet did not differ from data for cycling gilts. Data from this study indicated that insulin receptors of swine erythrocytes have binding characteristics similar to those in other species. Pregnancy and diet will alter insulin receptor binding in swine.

  13. Actin binding proteins and spermiogenesis

    Science.gov (United States)

    Mruk, Dolores D

    2011-01-01

    Drebrin E, an actin-binding protein lacking intrinsic activity in the regulation of actin dynamics (e.g., polymerization, capping, nucleation, branching, cross-linking, bundling and severing), is known to recruit actin regulatory proteins to a specific cellular site. Herein, we critically evaluate recent findings in the field which illustrate that drebrin E works together with two other actin-binding proteins, namely Arp3 (actin-related protein 3, a component of the Arp2/3 complex that simultaneously controls actin nucleation for polymerization and branching of actin filaments) and Eps8 (epidermal growth factor receptor pathway substrate 8 that controls capping of the barbed ends of actin filaments, as well as actin filament bundling) to regulate the homeostasis of F-actin filament bundles at the ectoplasmic specialization (ES), a testis-specific atypical adherens junction (AJ) in the seminiferous epithelium. This is mediated by the strict temporal and spatial expression of these three actin-binding proteins at the apical and basal ES at the Sertoli cell-spermatid (step 8–19) and Sertoli-Sertoli cell interface, respectively, during the seminiferous epithelial cycle of spermatogenesis. In this Commentary, we put forth a possible model by which drebrin E may be acting as a platform upon which proteins (e.g., Arp3) that are needed to alter the conformation of actin filament bundles at the ES can be recruited to the site, thus facilitating changes in cell shape and cell position in the epithelium during spermiogenesis and spermiation. In short, drebrin E may be acting as a “logistic” distribution center to manage different regulatory proteins at the apical ES, thereby regulating the dynamics of actin filament bundles and modulating the plasticity of the apical ES. This would allow adhesion to be altered continuously throughout the epithelial cycle to accommodate spermatid movement in the seminiferous epithelium during spermiogenesis and spermiation. We also

  14. Synthetic LPS-Binding Polymer Nanoparticles

    Science.gov (United States)

    Jiang, Tian

    Lipopolysaccharide (LPS), one of the principal components of most gram-negative bacteria's outer membrane, is a type of contaminant that can be frequently found in recombinant DNA products. Because of its strong and even lethal biological effects, selective LPS removal from bioproducts solution is of particular importance in the pharmaceutical and health care industries. In this thesis, for the first time, a proof-of-concept study on preparing LPS-binding hydrogel-like NPs through facile one-step free-radical polymerization was presented. With the incorporation of various hydrophobic (TBAm), cationic (APM, GUA) monomers and cross-linkers (BIS, PEG), a small library of NPs was constructed. Their FITC-LPS binding behaviors were investigated and compared with those of commercially available LPS-binding products. Moreover, the LPS binding selectivity of the NPs was also explored by studying the NPs-BSA interactions. The results showed that all NPs obtained generally presented higher FITC-LPS binding capacity in lower ionic strength buffer than higher ionic strength. However, unlike commercial poly-lysine cellulose and polymyxin B agarose beads' nearly linear increase of FITC-LPS binding with particle concentration, NPs exhibited serious aggregation and the binding quickly saturated or even decreased at high particle concentration. Among various types of NPs, higher FITC-LPS binding capacity was observed for those containing more hydrophobic monomers (TBAm). However, surprisingly, more cationic NPs with higher content of APM exhibited decreased FITC-LPS binding in high ionic strength conditions. Additionally, when new cationic monomer and cross-linker, GUA and PEG, were applied to replace APM and BIS, the obtained NPs showed improved FITC-LPS binding capacity at low NP concentration. But compared with APM- and BIS-containing NPs, the FITC-LPS binding capacity of GUA- and PEG-containing NPs saturated earlier. To investigate the NPs' binding to proteins, we tested the NPs

  15. Binding thermodynamics of a glutamate transporter homologue

    Science.gov (United States)

    Reyes, Nicolas; Oh, SeCheol; Boudker, Olga

    2013-01-01

    Glutamate transporters catalyze concentrative uptake of the neurotransmitter into glial cells and neurons. Their transport cycle involves binding and release of the substrate on the extra- and intracellular sides of the plasma membranes, and translocation of the substrate-binding site across the lipid bilayers. The energy of the ionic gradients, mainly sodium, fuels the cycle. Here, we used a cross-linking approach to trap a glutamate transporter homologue from Pyrococcus horikoshii in key conformational states with substrate-binding site facing either the extracellular or intracellular sides of the membrane to study their binding thermodynamics. We show that the chemical potential of sodium ions in solution is exclusively coupled to substrate binding and release, and not to substrate translocation. Despite the structural symmetry, the binding mechanisms are distinct on the opposite sides of the membrane and more complex than the current models suggest. PMID:23563139

  16. Characterization of feline serum-cobalt binding.

    Science.gov (United States)

    Schnelle, Amy N; Barger, Anne M; MacNeill, Amy L; Mitchell, Mark M; Solter, Philip

    2015-06-01

    Oxidative stress inhibits albumin's ability to complex with cobalt. Feline serum-cobalt binding has not been described. The objective was to develop a cobalt binding test for use with feline serum, and correlate the results with other biochemical and cellular constituents in blood, and with clinical diseases of cats. A colorimetric test of cobalt binding, based on the oxidation-reduction reaction of Co(+2) and dithiothreitol, was developed using feline serum. The test was used to measure cobalt binding in stored serum from 176 cats presented to the University of Illinois Veterinary Teaching Hospital for a variety of disease conditions. Time-matched hematology and biochemical data, and clinical information, were obtained from the medical record of each cat and correlated with the serum-cobalt binding results. Serial dilution of feline serum with phosphate-buffered saline resulted in a highly linear decrease in serum-cobalt binding (r(2)  = .9984). Serum-cobalt binding of the clinical samples also correlated with albumin concentrations in a stepwise linear regression model (r(2)  = .425), and both cobalt binding and albumin were significantly decreased in cases of inflammation. Albumin and cobalt binding also shared significant correlations with several erythron variables, and serum concentration of total calcium and bilirubin. The correlation of cobalt binding measured by a colorimetric test with albumin concentration in the clinical samples and with serum dilution is consistent with feline albumin-cobalt complex formation. Hypoalbuminemia is the likely cause of reduced serum-cobalt binding in inflammation and the correlations observed between cobalt binding and other variables. © 2015 American Society for Veterinary Clinical Pathology.

  17. Binding energy of the barbell exciton

    Science.gov (United States)

    Peeters, F. M.; Golub, J. E.

    1991-02-01

    The exciton binding energy in asymmetric coupled double quantum wells is calculated. As the system is electrically tuned from type I to type II, the exciton binding energy decreases from that of a two-dimensional exciton to the binding energy of a spatially separated electron-hole pair, i.e., the barbell exciton.$-- We compare our theoretical results with a recent experiment and find good agreement.

  18. CAP binding proteins associated with the nucleus.

    OpenAIRE

    Patzelt, E; Blaas, D; Kuechler, E

    1983-01-01

    Cap binding proteins of HeLa cells were identified by photo-affinity labelling using the cap analogue gamma-[32P]-[4-(benzoyl-phenyl)methylamido]-7-methylguanosine-5'- triphosphate. Photoreaction with whole cell homogenates resulted in specific labelling of five major polypeptides. The small molecular weight polypeptide appeared to be identical to the 24 000 to 26 000 dalton cap binding protein previously identified in initiation factors. A cap binding protein of 37 000 dalton was found in in...

  19. Mutated Leguminous Lectin Containing a Heparin-Binding like Motif in a Carbohydrate-Binding Loop Specifically Binds to Heparin.

    Directory of Open Access Journals (Sweden)

    Hirohito Abo

    Full Text Available We previously introduced random mutations in the sugar-binding loops of a leguminous lectin and screened the resulting mutated lectins for novel specificities using cell surface display. Screening of a mutated peanut agglutinin (PNA, revealed a mutated PNA with a distinct preference for heparin. Glycan microarray analyses using the mutated lectin fused to the Fc region of human immunoglobulin, revealed that a particular sulfated glycosaminoglycan (GAG, heparin, had the highest binding affinity for mutated PNA among 97 glycans tested, although wild-type PNA showed affinity towards Galβ1-3GalNAc and similar galactosylated glycans. Further analyses of binding specificity using an enzyme-linked immunoadsorbent assay demonstrated that the mutated PNA specifically binds to heparin, and weakly to de-2-O-sulfated heparin, but not to other GAG chains including de-6-O-sulfated and de-N-sulfated heparins. The mutated PNA had six amino acid substitutions within the eight amino acid-long sugar-binding loop. In this loop, the heparin-binding like motif comprised three arginine residues at positions 124, 128, and 129, and a histidine at position 125 was present. Substitution of each arginine or histidine residue to alanine reduced heparin-binding ability, indicating that all of these basic amino acid residues contributed to heparin binding. Inhibition assay demonstrated that heparin and dextran sulfate strongly inhibited mutated PNA binding to heparin in dose-dependent manner. The mutated PNA could distinguish between CHO cells and proteoglycan-deficient mutant cells. This is the first report establishing a novel leguminous lectin that preferentially binds to highly sulfated heparin and may provide novel GAG-binding probes to distinguish between heterogeneous GAG repeating units.

  20. Mutated Leguminous Lectin Containing a Heparin-Binding like Motif in a Carbohydrate-Binding Loop Specifically Binds to Heparin.

    Science.gov (United States)

    Abo, Hirohito; Soga, Keisuke; Tanaka, Atsuhiro; Tateno, Hiroaki; Hirabayashi, Jun; Yamamoto, Kazuo

    2015-01-01

    We previously introduced random mutations in the sugar-binding loops of a leguminous lectin and screened the resulting mutated lectins for novel specificities using cell surface display. Screening of a mutated peanut agglutinin (PNA), revealed a mutated PNA with a distinct preference for heparin. Glycan microarray analyses using the mutated lectin fused to the Fc region of human immunoglobulin, revealed that a particular sulfated glycosaminoglycan (GAG), heparin, had the highest binding affinity for mutated PNA among 97 glycans tested, although wild-type PNA showed affinity towards Galβ1-3GalNAc and similar galactosylated glycans. Further analyses of binding specificity using an enzyme-linked immunoadsorbent assay demonstrated that the mutated PNA specifically binds to heparin, and weakly to de-2-O-sulfated heparin, but not to other GAG chains including de-6-O-sulfated and de-N-sulfated heparins. The mutated PNA had six amino acid substitutions within the eight amino acid-long sugar-binding loop. In this loop, the heparin-binding like motif comprised three arginine residues at positions 124, 128, and 129, and a histidine at position 125 was present. Substitution of each arginine or histidine residue to alanine reduced heparin-binding ability, indicating that all of these basic amino acid residues contributed to heparin binding. Inhibition assay demonstrated that heparin and dextran sulfate strongly inhibited mutated PNA binding to heparin in dose-dependent manner. The mutated PNA could distinguish between CHO cells and proteoglycan-deficient mutant cells. This is the first report establishing a novel leguminous lectin that preferentially binds to highly sulfated heparin and may provide novel GAG-binding probes to distinguish between heterogeneous GAG repeating units.

  1. Quantifying Stress in Marine Mammals: Measuring Biologically Active Cortisol in Cetaceans and Pinnipeds

    Science.gov (United States)

    2015-09-30

    boonstra/ LONG-TERM GOALS This research will improve our ability to measure stress in marine mammals. Stress hormones (glucocorticoids...are best estimated by measuring “free glucocorticoid” levels (i.e. that hormone not bound by CBG). This project will improve the capacity of marine...stage, and stress history , so it is critical to measure CBG binding capacity from as diverse a group of individuals as possble. APPROACH

  2. 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...

  3. 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....

  4. Parathyroid hormone binding to cultured avian osteoclasts

    Energy Technology Data Exchange (ETDEWEB)

    Teti, A.; Rizzoli, R.; Zambonin Zallone, A. (Univ. of Bari (Italy))

    1991-02-14

    Parathyroid hormone (PTH) increases serum calcium concentration via a controversial cellular mechanism. We investigated whether PTH binds avian osteoclasts. Isolated hypocalcaemic hen osteoclasts were incubated with ({sup 125}I)--bovine PTH (1-84). Specific binding of the hormone to the cells, which reached the equilibrium within 60 min, was observed. Half maximal binding was reached by 10 min. Binding was competitively inhibited by increasing doses of unlabeled PTH, and was about 55% displaced by adding, at the equilibrium, 10(-6) M unlabeled PTH. Autoradiography demonstrated specific label on the osteoclast. The cellular mechanism activated by the hormone remains to be elucidated.

  5. 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

  6. 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.

  7. 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 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.

  8. Tissue specificity of endothelin binding sites

    Energy Technology Data Exchange (ETDEWEB)

    Bolger, G.T.; Liard, F.; Krogsrud, R.; Thibeault, D.; Jaramillo, J. (BioMega, Inc., Laval, Quebec (Canada))

    1990-09-01

    A measurement was made of the binding of 125I-labeled endothelin (125I-ET) to crude membrane fractions prepared from rat aorta, atrium, ventricle, portal vein, trachea, lung parenchyma, vas deferens, ileum, bladder, and guinea-pig taenia coli and lung parenchyma. Scatchard analysis of 125I-ET binding in all tissues indicated binding to a single class of saturable sites. The affinity and density of 125I-ET binding sites varied between tissues. The Kd of 125I-ET binding was approximately 0.5 nM for rat aorta, trachea, lung parenchyma, ventricle, bladder, and vas deferens, and guinea-pig taenia coli and lung parenchyma, 1.8 nM for rat portal vein and atrium, and 3.3 nM for ileum. The Bmax of 125I-ET binding had the following rank order of density in rat tissues: trachea greater than lung parenchyma = vas deferens much greater than aorta = portal vein = atrium greater than bladder greater than ventricle = ileum. The properties of 125I-ET endothelin binding were characterized in rat ventricular membranes. 125I-ET binding was time dependent, reaching a maximum within 45-60 min at 25 degrees C. The calculated microassociation constant was 9.67 x 10(5) s-1 M-1. Only 15-20% of 125I-ET dissociated from its binding site even when dissociation was studied as long as 3 h. Preincubation of ventricular membranes with ET prevented binding of 125I-ET. 125I-ET binding was destroyed by boiling of ventricular membranes and was temperature, pH, and cation (Ca2+, Mg2+, and Na+) dependent.

  9. 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

  10. 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.

  11. 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.

  12. Thermodynamics of Ligand Binding to Acyl-Coenzyme A Binding Protein Studied by Titration Calorimetry

    DEFF Research Database (Denmark)

    Færgeman, Nils Joakim; Sigurskjold, Bent Walther; Kragelund, Birthe 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-...

  13. 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-...

  14. 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.

  15. 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...

  16. Neurotransmitter Receptor Binding in Bovine Cerebral Microvessels

    Science.gov (United States)

    Peroutka, Stephen J.; Moskowitz, Michael A.; Reinhard, John F.; Synder, Solomon H.

    1980-05-01

    Purified preparations of microvessels from bovine cerebral cortex contain substantial levels of alpha-adrenergic, beta-adrenergic, and histamine 1 receptor binding sites but only negligible serotonin, muscarinic cholinergic, opiate, and benzodiazepine receptor binding. Norepinephrine and histamine may be endogenous regulators of the cerebral microcirculation at the observed receptors.

  17. 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 ...

  18. 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.

  19. 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...

  20. (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.

  1. Ethylene binding site affinity in ripening apples

    Energy Technology Data Exchange (ETDEWEB)

    Blankenship, S.M. (North Carolina State Univ., Raleigh, NC (United States). Dept. of Horticultural Science); Sisler, E.C. (North Carolina State Univ., Raleigh, NC (United States))

    1993-09-01

    Scatchard plots for ethylene binding in apples (Malus domestica Borkh.), which were harvested weekly for 5 weeks to include the ethylene climacteric rise, showed C[sub 50] values (concentration of ethylene needed to occupy 50% of the ethylene binding sites) of 0.10, 0.11, 0.34, 0.40, and 0.57 [mu]l ethylene/liter[sup [minus]1], respectively, for each of the 5 weeks. Higher ethylene concentrations were required to saturate the binding sites during the climacteric rise than at other times. Diffusion of [sup 14]C-ethylene from the binding sites was curvilinear and did not show any indication of multiple binding sites. Ethylene was not metabolized by apple tissue.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Thermodynamic binding constants for gallium transferrin

    Energy Technology Data Exchange (ETDEWEB)

    Harris, W.R.; Pecoraro, V.L.

    1983-01-18

    Gallium-67 is widely used as an imaging agent for tumors and inflammatory abscesses. It is well stablished that Ga/sup 3 +/ travels through the circulatory system bound to the serum iron transport protein transferrin and that this protein binding is an essential step in tumor localization. However, there have been conflicting reports on the magnitude of the gallium-transferrin binding constants. Therefore, thermodynamic binding constants for gallium complexation at the two specific metal binding sites of human serum transferrin at pH 7.4 and 5 mM NaHCO/sub 3/ have been determined by UV difference spectroscopy. The conditional constants calculated for 27 mM NaHCO/sub 3/ are log K/sub 1/* = 20.3 and log K/sub 2/* = 19.3. These results are discussed in relation to the thermodynamics of transferrin binding of Fe/sup 3 +/ and to previous reports on gallium binding. The strength of transferrin complexation is also compared to that of a series of low molecular weight ligands by using calculated pM values (pM = -log (Ga(H/sub 2/O)/sub 6/)) to express the effective binding strength at pH 7.4.

  8. Myeloperoxidase selectively binds and selectively kills microbes.

    Science.gov (United States)

    Allen, Robert C; Stephens, Jackson T

    2011-01-01

    Myeloperoxidase (MPO) is reported to selectively bind to bacteria. The present study provides direct evidence of MPO binding selectivity and tests the relationship of selective binding to selective killing. The microbicidal effectiveness of H(2)O(2) and of OCl(-) was compared to that of MPO plus H(2)O(2). Synergistic microbicidal action was investigated by combining Streptococcus sanguinis, a H(2)O(2)-producing microbe showing low MPO binding, with high-MPO-binding Escherichia coli, Staphylococcus aureus, or Pseudomonas aeruginosa without exogenous H(2)O(2), with and without MPO, and with and without erythrocytes (red blood cells [RBCs]). Selectivity of MPO microbicidal action was conventionally measured as the MPO MIC and minimal bactericidal concentration (MBC) for 82 bacteria including E. coli, P. aeruginosa, S. aureus, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus agalactiae, and viridans streptococci. Both H(2)O(2) and OCl(-) destroyed RBCs at submicrobicidal concentrations. Nanomolar concentrations of MPO increased H(2)O(2) microbicidal action 1,000-fold. Streptococci plus MPO produced potent synergistic microbicidal action against all microbes tested, and RBCs caused only a small decrease in potency without erythrocyte damage. MPO directly killed H(2)O(2)-producing S. pyogenes but was ineffective against non-H(2)O(2)-producing E. faecalis. The MPO MICs and MBCs for E. coli, P. aeruginosa, and S. aureus were significantly lower than those for E. faecalis. The streptococcal studies showed much higher MIC/MBC results, but such testing required lysed horse blood-supplemented medium, thus preventing valid comparison of these results to those for the other microbes. E. faecalis MPO binding is reportedly weak compared to binding of E. coli, P. aeruginosa, and S. aureus but strong compared to binding of streptococci. Selective MPO binding results in selective killing.

  9. 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

  10. Druggability of methyl-lysine binding sites

    Science.gov (United States)

    Santiago, C.; Nguyen, K.; Schapira, M.

    2011-12-01

    Structural modules that specifically recognize—or read—methylated or acetylated lysine residues on histone peptides are important components of chromatin-mediated signaling and epigenetic regulation of gene expression. Deregulation of epigenetic mechanisms is associated with disease conditions, and antagonists of acetyl-lysine binding bromodomains are efficacious in animal models of cancer and inflammation, but little is known regarding the druggability of methyl-lysine binding modules. We conducted a systematic structural analysis of readers of methyl marks and derived a predictive druggability landscape of methyl-lysine binding modules. We show that these target classes are generally less druggable than bromodomains, but that some proteins stand as notable exceptions.

  11. 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…

  12. 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...

  13. HEAVY QUARK POTENTIALS AND QUARKONIA BINDING.

    Energy Technology Data Exchange (ETDEWEB)

    PETRECZKY,P.

    2004-11-04

    The author reviews recent progress in studying in-medium modification of inter-quark forces at finite temperature in lattice QCD. Some applications to the problem of quarkonium binding in potential models is also discussed.

  14. 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...

  15. Adjustment of legally binding local plans

    DEFF Research Database (Denmark)

    Hvingel, Line Træholt; Aunsborg, Christian; Christensen, Finn Kjær

    2012-01-01

    Traditionally, and by law, new urban areas in Denmark are regulated and planned through legally binding local plans. Recently a tendency has occurred: The municipalities make the legally binding local plans quite open for future adjustment, and they are using a substantial amount of ‘empowerment......, which seem to be beyond the scope of the Danish Planning Act. This paper deals with this problem through case studies and a legal analysis of present law. If the combination of the legally binding local plan and subsequent added requirements is misused, it will weaken the legal rights of the citizens...... the considerations of legal rights, the extend of the legal use of empowerment provisions and the combination of the use of legal binding local plans and other legal instruments such as easements and sales agreements....

  16. AN INDIVIDUALIZED APPROACH TO THE EVALUATION OF CUSHING SYNDROME.

    Science.gov (United States)

    Sharma, Susmeeta T

    2017-06-01

    Cushing syndrome (CS) is caused by chronic exposure to excess glucocorticoids. Early recognition and treatment of hypercortisolemia can lead to decreased morbidity and mortality. The diagnosis of CS and thereafter, establishing the cause can often be difficult, especially in patients with mild and cyclic hypercortisolism. Surgical excision of the cause of excess glucocorticoids is the optimal treatment for CS. Medical therapy (steroidogenesis inhibitors, medications that decrease adrenocorticotropic hormone [ACTH] levels or glucocorticoid antagonists) and pituitary radiotherapy may be needed as adjunctive treatment modalities in patients with residual, recurrent or metastatic disease, in preparation for surgery, or when surgery is contraindicated. A multidisciplinary team approach, individualized treatment plan and long-term follow-up are important for optimal management of hypercortisolemia and the comorbidities associated with CS. ACTH = adrenocorticotropic hormone; BIPSS = bilateral inferior petrosal sinus sampling; CBG = corticosteroid-binding globulin; CD = Cushing disease; CRH = corticotropin-releasing hormone; CS = Cushing syndrome; Dex = dexamethasone; DST = dexamethasone suppression test; EAS = ectopic ACTH syndrome; FDA = U.S. Food & Drug Administration; HDDST = high-dose DST; IPS/P = inferior petrosal sinus to peripheral; MRI = magnetic resonance imaging; NET = neuroendocrine tumor; PET = positron emission tomography; UFC = urinary free cortisol.

  17. 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.

  18. Antimicrobial activities of heparin-binding peptides.

    OpenAIRE

    Andersson, Emma; Rydengård, Victoria; Sonesson, Andreas; Mörgelin, Matthias; Björck, Lars; Schmidtchen, Artur

    2004-01-01

    Antimicrobial peptides are effector molecules of the innate immune system. We recently showed that the human antimicrobial peptides alpha-defensin and LL-37 bind to glycosaminoglycans (heparin and dermatan sulphate). Here we demonstrate the obverse, i.e. structural motifs associated with heparin affinity (cationicity, amphipaticity, and consensus regions) may confer antimicrobial properties to a given peptide. Thus, heparin-binding peptides derived from laminin isoforms, von Willebrand factor...

  19. Electrostatically biased binding of kinesin to microtubules.

    Directory of Open Access Journals (Sweden)

    Barry J Grant

    2011-11-01

    Full Text Available The minimum motor domain of kinesin-1 is a single head. Recent evidence suggests that such minimal motor domains generate force by a biased binding mechanism, in which they preferentially select binding sites on the microtubule that lie ahead in the progress direction of the motor. A specific molecular mechanism for biased binding has, however, so far been lacking. Here we use atomistic Brownian dynamics simulations combined with experimental mutagenesis to show that incoming kinesin heads undergo electrostatically guided diffusion-to-capture by microtubules, and that this produces directionally biased binding. Kinesin-1 heads are initially rotated by the electrostatic field so that their tubulin-binding sites face inwards, and then steered towards a plus-endwards binding site. In tethered kinesin dimers, this bias is amplified. A 3-residue sequence (RAK in kinesin helix alpha-6 is predicted to be important for electrostatic guidance. Real-world mutagenesis of this sequence powerfully influences kinesin-driven microtubule sliding, with one mutant producing a 5-fold acceleration over wild type. We conclude that electrostatic interactions play an important role in the kinesin stepping mechanism, by biasing the diffusional association of kinesin with microtubules.

  20. 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.

  1. 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

  2. Identification of pseudomurein cell wall binding domains.

    Science.gov (United States)

    Steenbakkers, Peter J M; Geerts, Wim J; Ayman-Oz, Nilgün A; Keltjens, Jan T

    2006-12-01

    Methanothermobacter thermautotrophicus is a methanogenic Gram-positive microorganism with a cell wall consisting of pseudomurein. Currently, no information is available on extracellular pseudomurein biology and so far only two prophage pseudomurein autolysins, PeiW and PeiP, have been reported. In this paper we show that PeiW and PeiP contain two different N-terminal pseudomurein cell wall binding domains. This finding was used to identify a novel domain, PB007923, on the M. thermautotrophicus genome present in 10 predicted open reading frames. Three homologues were identified in the Methanosphaera stadtmanae genome. Binding studies of fusion constructs of three separate PB007923 domains to green fluorescent protein revealed that it also constituted a cell wall binding domain. Both prophage domains and the PB007923 domain bound to the cell walls of Methanothermobacter species and fluorescence microscopy showed a preference for the septal region. Domain specificities were revealed by binding studies with other pseudomurein-containing archaea. Localized binding was observed for M. stadtmanae and Methanobrevibacter species, while others stained evenly. The identification of the first pseudomurein cell wall binding domains reveals the dynamics of the pseudomurein cell wall and provides marker proteins to study the extracellular pseudomurein biology of M. thermautotrophicus and of other pseudomurein-containing archaea.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Immobilized purified folate-binding protein: binding characteristics and use for quantifying folate in erythrocytes

    International Nuclear Information System (INIS)

    Hansen, S.I.; Holm, J.; Nexo, E.

    1987-01-01

    Purified folate-binding protein from cow's milk was immobilized on monodisperse polymer particles (Dynospheres) activated by rho-toluenesulfonyl chloride. Leakage from the spheres was less than 0.1%, and the binding properties were similar to those of the soluble protein with regard to dissociation, pH optimum for binding pteroylglutamic acid, and specificity for binding various folate derivatives. We used the immobilized folate-binding protein as binding protein in an isotope-dilution assay for quantifying folate in erythrocytes. The detection limit was 50 nmol/L and the CV over a six-month period was 2.3% (means = 1.25 mumol/L, n = 15). The reference interval, for folate measured in erythrocytes of 43 blood donors, was 0.4-1.5 mumol/L

  8. To Bind or not to Bind: It’s in the Contract

    DEFF Research Database (Denmark)

    Tvarnø, Christina D.

    2015-01-01

    This article discusses the formalization of collaboration through partnering contracts in the construction industry in the USA, Great Britain and Denmark. The article compares the different types of collaborative partnering contracts in the three countries, and provides a conclusion on whether...... the collaborative partnering contract should be binding or non-binding, based on the three empirical contracts analyzed in this article. The partnering contracts in Great Britain and Denmark are legally binding, while in the USA the partnering agreements are non-binding charters or letters of intent. This article...... discusses, in a theoretical perspective, the legal reasoning behind the different partnering approaches, both from a historical and contract law perspective, and furthermore applies a game theoretical approach in evaluating binding versus non-binding partnering contracts. The analysis focuses on private...

  9. Crystal Structure of the Botulinum Neurotoxin Type G Binding Domain: Insight into Cell Surface Binding

    Energy Technology Data Exchange (ETDEWEB)

    Stenmark, Pål; Dong, Min; Dupuy, Jérôme; Chapman, Edwin R.; Stevens, Raymond C. (Scripps); (UW)

    2011-11-02

    Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-{angstrom} X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantly reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent.

  10. Are many Z-DNA binding proteins actually phospholipid-binding proteins?

    OpenAIRE

    Krishna, P; Kennedy, B P; Waisman, D M; van de Sande, J H; McGhee, J D

    1990-01-01

    We used a Z-DNA affinity column to isolate a collection of Z-DNA binding proteins from a high salt extract of Escherichia coli. We identified one of the major Z-DNA binding proteins of this fraction, not as a protein involved in gene regulation or genetic recombination, but rather as an outer membrane porin protein. We then showed that several other known phospholipid-binding proteins (bovine lung annexins and human serum lipoproteins) also bind much more tightly to Z-DNA than to B-DNA. In al...

  11. 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...

  12. Mannose-binding geometry of pradimicin A.

    Science.gov (United States)

    Nakagawa, Yu; Doi, Takashi; Taketani, Takara; Takegoshi, K; Igarashi, Yasuhiro; Ito, Yukishige

    2013-08-05

    Pradimicins (PRMs) and benanomicins are the only family of non-peptidic natural products with lectin-like properties, that is, they recognize D-mannopyranoside (Man) in the presence of Ca(2+) ions. Coupled with their unique Man binding ability, they exhibit antifungal and anti-HIV activities through binding to Man-containing glycans of pathogens. Notwithstanding the great potential of PRMs as the lectin mimics and therapeutic leads, their molecular basis of Man recognition has yet to be established. Their aggregate-forming propensity has impeded conventional interaction analysis in solution, and the analytical difficulty is exacerbated by the existence of two Man binding sites in PRMs. In this work, we investigated the geometry of the primary Man binding of PRM-A, an original member of PRMs, by the recently developed analytical strategy using the solid aggregate composed of the 1:1 complex of PRM-A and Man. Evaluation of intermolecular distances by solid-state NMR spectroscopy revealed that the C2-C4 region of Man is in close contact with the primary binding site of PRM-A, while the C1 and C6 positions of Man are relatively distant. The binding geometry was further validated by co-precipitation experiments using deoxy-Man derivatives, leading to the proposal that PRM-A binds not only to terminal Man residues at the non-reducing end of glycans, but also to internal 6-substituted Man residues. The present study provides new insights into the molecular basis of Man recognition and glycan specificity of PRM-A. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. 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.

  14. 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.

  15. Haptenation: Chemical Reactivity and Protein Binding

    Directory of Open Access Journals (Sweden)

    Itai Chipinda

    2011-01-01

    Full Text Available Low molecular weight chemical (LMW allergens are commonly referred to as haptens. Haptens must complex with proteins to be recognized by the immune system. The majority of occupationally related haptens are reactive, electrophilic chemicals, or are metabolized to reactive metabolites that form covalent bonds with nucleophilic centers on proteins. Nonelectrophilic protein binding may occur through disulfide exchange, coordinate covalent binding onto metal ions on metalloproteins or of metal allergens, themselves, to the major histocompatibility complex. Recent chemical reactivity kinetic studies suggest that the rate of protein binding is a major determinant of allergenic potency; however, electrophilic strength does not seem to predict the ability of a hapten to skew the response between Th1 and Th2. Modern proteomic mass spectrometry methods that allow detailed delineation of potential differences in protein binding sites may be valuable in predicting if a chemical will stimulate an immediate or delayed hypersensitivity. Chemical aspects related to both reactivity and protein-specific binding are discussed.

  16. Computational search for aflatoxin binding proteins

    Science.gov (United States)

    Wang, Ying; Liu, Jinfeng; Zhang, Lujia; He, Xiao; Zhang, John Z. H.

    2017-10-01

    Aflatoxin is one of the mycotoxins that contaminate various food products. Among various aflatoxin types (B1, B2, G1, G2 and M1), aflatoxin B1 is the most important and the most toxic one. In this study, through computational screening, we found that several proteins may bind specifically with different type of aflatoxins. Combination of theoretical methods including target fishing, molecular docking, molecular dynamics (MD) simulation, MM/PBSA calculation were utilized to search for new aflatoxin B1 binding proteins. A recently developed method for calculating entropic contribution to binding free energy called interaction entropy (IE) was employed to compute the binding free energy between the protein and aflatoxin B1. Through comprehensive comparison, three proteins, namely, trihydroxynaphthalene reductase, GSK-3b, and Pim-1 were eventually selected as potent aflatoxin B1 binding proteins. GSK-3b and Pim-1 are drug targets of cancers or neurological diseases. GSK-3b is the strongest binder for aflatoxin B1.

  17. Engineering Escherichia coli to bind to cyanobacteria.

    Science.gov (United States)

    Zhang, Zijian; Meng, Liuyi; Ni, Congjian; Yao, Lanqiu; Zhang, Fengyu; Jin, Yuji; Mu, Xuelang; Zhu, Shiyu; Lu, Xiaoyu; Liu, Shiyu; Yu, Congyu; Wang, Chenggong; Zheng, Pu; Wu, Jie; Kang, Li; Zhang, Haoqian M; Ouyang, Qi

    2017-03-01

    We engineered Escherichia coli cells to bind to cyanobacteria by heterologously producing and displaying lectins of the target cyanobacteria on their surface. To prove the efficacy of our approach, we tested this design on Microcystis aeruginosa with microvirin (Mvn), the lectin endogenously produced by this cyanobacterium. The coding sequence of Mvn was C-terminally fused to the ice nucleation protein NC (INPNC) gene and expressed in E. coli. Results showed that E. coli cells expressing the INPNC::Mvn fusion protein were able to bind to M. aeruginosa and the average number of E. coli cells bound to each cyanobacterial cell was enhanced 8-fold. Finally, a computational model was developed to simulate the binding reaction and help reconstruct the binding parameters. To our best knowledge, this is the first report on the binding of two organisms in liquid culture mediated by the surface display of lectins and it may serve as a novel approach to mediate microbial adhesion. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  18. 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.).

  19. 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.

  20. 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...... in aqueous compartments. - Bojesen, I. N., and H. S. Hansen. Binding of anandamide to bovine serum albumin.......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...

  1. 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.

  2. 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).

  3. Estrogen receptor diminishes DNA-binding activities of chicken GATA-1 and CACCC-binding proteins.

    Science.gov (United States)

    Holth, L T; Sun, J M; Coutts, A S; Murphy, L C; Davie, J R

    1997-12-01

    The estrogen receptor (ER) repressed erythroid differentiation and erythroid-specific gene expression. In this study, we investigated the effect of ER alpha (referred to throughout as ER) on DNA-binding activities of transcription factors involved in regulating the expression of erythroid-specific genes, and, in particular, the histone H5 gene. Using electrophoretic mobility shift assays, we found that in the presence of rabbit reticulocyte lysate, human ER reduced the binding activities of chicken immature erythrocyte nuclear extracted proteins to GATA and CACCC sites in the H5 promoter and enhancer. In contrast, the binding activities of NF1 and Sp1 were not affected by ER. Binding of ER to an estrogen response element was enhanced by addition of rabbit reticulocyte lysate. This lysate was also necessary for ER to diminish the DNA-binding activity of GATA-1. These results suggest that additional factor(s) are necessary for full ER function. Both GATA-1 and CACCC-binding proteins are critical for the developmentally regulated expression of erythroid-specific genes. We hypothesize that interference in DNA-binding activities of GATA-1 and CACCC-binding proteins is the mechanism by which the ER inhibits regulation of these genes.

  4. 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

  5. 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.

  6. Salt-mediated two-site ligand binding by the cocaine-binding aptamer.

    Science.gov (United States)

    Neves, Miguel A D; Slavkovic, Sladjana; Churcher, Zachary R; Johnson, Philip E

    2017-02-17

    Multisite ligand binding by proteins is commonly utilized in the regulation of biological systems and exploited in a range of biochemical technologies. Aptamers, although widely utilized in many rationally designed biochemical systems, are rarely capable of multisite ligand binding. The cocaine-binding aptamer is often used for studying and developing sensor and aptamer-based technologies. Here, we use isothermal titration calorimetry (ITC) and NMR spectroscopy to demonstrate that the cocaine-binding aptamer switches from one-site to two-site ligand binding, dependent on NaCl concentration. The high-affinity site functions at all buffer conditions studied, the low-affinity site only at low NaCl concentrations. ITC experiments show the two ligand-binding sites operate independently of one another with different affinities and enthalpies. NMR spectroscopy shows the second binding site is located in stem 2 near the three-way junction. This ability to control ligand binding at the second site by adjusting the concentration of NaCl is rare among aptamers and may prove a useful in biotechnology applications. This work also demonstrates that in vitro selected biomolecules can have functions as complex as those found in nature. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. 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 ...

  8. HLA-C KIR-Ligands Determine the Impact of Anti-Thymocyte Globulin (ATG) on Graft versus Host and Graft versus Leukemia Effects Following Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Clausen, Johannes; Böhm, Alexandra; Straßl, Irene; Stiefel, Olga; Buxhofer-Ausch, Veronika; Machherndl-Spandl, Sigrid; König, Josef; Schmidt, Stefan; Steitzer, Hansjörg; Danzer, Martin; Kasparu, Hedwig; Weltermann, Ansgar; Nachbaur, David

    2017-03-28

    Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk factor for severe aGVHD. Congruously, we have previously reported favorable outcomes in C1/1 recipients after ATG-based transplants in a monocentric analysis. Here, within an extended cohort, we test the hypothesis that incorporation of ATG for GVHD prophylaxis may improve survival particularly in HSCT recipients with at least one C1 KIR-ligand. Retrospectively, 775 consecutive allogeneic (excluding haploidentical) HSCTs were analyzed, including peripheral blood and bone marrow grafts for adults with hematological diseases at two Austrian HSCT centers. ATG-Fresenius/Grafalon, Thymoglobuline, and alemtuzumab were applied in 256, 87, and 7 transplants, respectively (subsequently summarized as "ATG"), while 425 HSCT were performed without ATG. Median follow-up of surviving patients is 48 months. Adjusted for age, disease-risk, HLA-match, donor and graft type, sex match, cytomegalovirus serostatus, conditioning intensity, and type of post-grafting GVHD prophylaxis, Cox regression analysis of the entire cohort ( n = 775) revealed a significant association of ATG with decreased non-relapse mortality (NRM) (risk ratio (RR), 0.57; p = 0.001), and overall mortality (RR, 0.71; p = 0.014). Upon stratification for HLA-C KIR-L, the greatest benefit for ATG emerged in C1/1 recipients ( n = 291), by reduction of non-relapse (RR, 0.34; p = 0.0002) and overall mortality (RR, 0.50; p = 0.003). Less pronounced, ATG decreased NRM (RR, 0.60; p = 0.036) in HLA-C group 1/2 recipients ( n = 364

  9. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial.

    Science.gov (United States)

    Finke, Jürgen; Bethge, Wolfgang A; Schmoor, Claudia; Ottinger, Hellmut D; Stelljes, Matthias; Zander, Axel R; Volin, Liisa; Ruutu, Tapani; Heim, Dominik A; Schwerdtfeger, Rainer; Kolbe, Karin; Mayer, Jiri; Maertens, Johan A; Linkesch, Werner; Holler, Ernst; Koza, Vladimir; Bornhäuser, Martin; Einsele, Hermann; Kolb, Hans-Jochem; Bertz, Hartmut; Egger, Matthias; Grishina, Olga; Socié, Gérard

    2009-09-01

    Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic haematopoietic cell transplantation from unrelated donors. Anti-T-cell globulins (ATGs) might lower the incidence of GVHD. We did a prospective, randomised, multicentre, open-label, phase 3 trial to compare standard GVHD prophylaxis with ciclosporin and methotrexate with or without anti-Jurkat ATG-Fresenius (ATG-F). Between May 26, 2003, and Feb 8, 2007, 202 patients with haematological malignancies were centrally randomly assigned using computer-generated centre-stratified block randomisation between treatment groups receiving ciclosporin and methotrexate with or without additional ATG-F. One patient in the ATG-F group did not undergo transplantation, thus 201 patients who underwent transplantation with peripheral blood (n=164; 82%) or bone marrow (n=37; 18%) grafts from unrelated donors after myeloablative conditioning were included in the full analysis set, and were analysed according to their randomly assigned treatment (ATG-F n=103, control n=98). The primary endpoint was severe acute GVHD (aGVHD) grade III-IV or death within 100 days of transplantation. The trial is registered with the numbers DRKS00000002 and NCT00655343. The number of patients in the ATG-F group who had severe aGVHD grade III-IV or who died within 100 days of transplantation was 12 and 10 (21.4%, 95% CI 13.4-29.3), respectively, compared with 24 and nine (33.7%, 24.3-43.0) patients, respectively, in the control group (adjusted odds ratio 0.59, 95% CI 0.30-1.17; p=0.13). The cumulative incidence of aGVHD grade III-IV was 11.7% (95% CI 6.8-19.8) in the ATG-F group versus 24.5% (17.3-34.7) in the control group (adjusted hazard ratio [HR] 0.50, 95% CI 0.25-1.01; p=0.054), and cumulative incidence of aGVHD grade II-IV was 33.0% (n=34; 95% CI 25.1-43.5) in the ATG-F group versus 51.0% (n=50; 95% CI 42.0-61.9) in the control group (adjusted HR 0.56, 0.36-0.87; p=0.011). The 2-year cumulative incidence of

  10. Opioid binding sites in the guinea pig and rat kidney: Radioligand homogenate binding and autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Dissanayake, V.U.; Hughes, J.; Hunter, J.C. (Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge (England))

    1991-07-01

    The specific binding of the selective {mu}-, {delta}-, and {kappa}-opioid ligands (3H)(D-Ala2,MePhe4,Gly-ol5)enkephalin ((3H) DAGOL), (3H)(D-Pen2,D-Pen5)enkephalin ((3H)DPDPE), and (3H)U69593, respectively, to crude membranes of the guinea pig and rat whole kidney, kidney cortex, and kidney medulla was investigated. In addition, the distribution of specific 3H-opioid binding sites in the guinea pig and rat kidney was visualized by autoradiography. Homogenate binding and autoradiography demonstrated the absence of {mu}- and {kappa}-opioid binding sites in the guinea pig kidney. No opioid binding sites were demonstrable in the rat kidney. In the guinea pig whole kidney, cortex, and medulla, saturation studies demonstrated that (3H)DPDPE bound with high affinity (KD = 2.6-3.5 nM) to an apparently homogeneous population of binding sites (Bmax = 8.4-30 fmol/mg of protein). Competition studies using several opioid compounds confirmed the nature of the {delta}-opioid binding site. Autoradiography experiments demonstrated that specific (3H)DPDPE binding sites were distributed radially in regions of the inner and outer medulla and at the corticomedullary junction of the guinea pig kidney. Computer-assisted image analysis of saturation data yielded KD values (4.5-5.0 nM) that were in good agreement with those obtained from the homogenate binding studies. Further investigation of the {delta}-opioid binding site in medulla homogenates, using agonist ((3H)DPDPE) and antagonist ((3H)diprenorphine) binding in the presence of Na+, Mg2+, and nucleotides, suggested that the {delta}-opioid site is linked to a second messenger system via a GTP-binding protein. Further studies are required to establish the precise localization of the {delta} binding site in the guinea pig kidney and to determine the nature of the second messenger linked to the GTP-binding protein in the medulla.

  11. Binding of alkylpyridinium chloride surfactants to sodium polystyrene sulfonate

    NARCIS (Netherlands)

    Ishiguro, M.; Koopal, L.K.

    2009-01-01

    Binding of cationic surfactants to anionic polymers is well studied. However, the surfactant binding characteristics at very low concentration near the start of binding and at high concentration, where charge compensation may Occur. are less well known. Therefore, the binding characteristics of

  12. Asporin competes with decorin for collagen binding, binds calcium and promotes osteoblast collagen mineralization

    DEFF Research Database (Denmark)

    Kalamajski, Sebastian; Aspberg, Anders; Lindblom, Karin

    2009-01-01

    The interactions of the ECM (extracellular matrix) protein asporin with ECM components have previously not been investigated. Here, we show that asporin binds collagen type I. This binding is inhibited by recombinant asporin fragment LRR (leucine-rich repeat) 10-12 and by full-length decorin......, but not by biglycan. We demonstrate that the polyaspartate domain binds calcium and regulates hydroxyapatite formation in vitro. In the presence of asporin, the number of collagen nodules, and mRNA of osteoblastic markers Osterix and Runx2, were increased. Moreover, decorin or the collagen-binding asporin fragment...... LRR 10-12 inhibited the pro-osteoblastic activity of full-length asporin. Our results suggest that asporin and decorin compete for binding to collagen and that the polyaspartate in asporin directly regulates collagen mineralization. Therefore asporin has a role in osteoblast-driven collagen...

  13. AUXIN BINDING PROTEIN1: the outsider.

    Science.gov (United States)

    Sauer, Michael; Kleine-Vehn, Jürgen

    2011-06-01

    AUXIN BINDING PROTEIN1 (ABP1) is one of the first characterized proteins that bind auxin and has been implied as a receptor for a number of auxin responses. Early studies characterized its auxin binding properties and focused on rapid electrophysiological and cell expansion responses, while subsequent work indicated a role in cell cycle and cell division control. Very recently, ABP1 has been ascribed a role in modulating endocytic events at the plasma membrane and RHO OF PLANTS-mediated cytoskeletal rearrangements during asymmetric cell expansion. The exact molecular function of ABP1 is still unresolved, but its main activity apparently lies in influencing events at the plasma membrane. This review aims to connect the novel findings with the more classical literature on ABP1 and to point out the many open questions that still separate us from a comprehensive model of ABP1 action, almost 40 years after the first reports of its existence.

  14. The binding of Np to rat bone

    International Nuclear Information System (INIS)

    Ramounet, B.; Taylor, D.M.

    1997-01-01

    Neptunium has been shown to massively deposit in bone, after intravenous or intramuscular injections. Initially, it was uniformly distributed on periosteal and endosteal bone surfaces. The nature of the binding molecules, for this actinide, in the skeleton, has not yet been identified. The aim of this work was to characterize the ligands of neptunium by selective extractions of bone components. The preliminary results displayed the binding of 237 Np(IV) in the organic phase of bone, after intravenous or intramuscular contamination. Further studies are in progress, to quantify the fraction of Np bound to the organic and mineral compartment of bone, and to determine the affinity constant and the turn-over of the binding proteins. (authors)

  15. Mucin Binding Reduces Colistin Antimicrobial Activity

    Science.gov (United States)

    Huang, Johnny X.; Blaskovich, Mark A. T.; Pelingon, Ruby; Ramu, Soumya; Kavanagh, Angela; Elliott, Alysha G.; Butler, Mark S.

    2015-01-01

    Colistin has found increasing use in treating drug-resistant bacterial lung infections, but potential interactions with pulmonary biomolecules have not been investigated. We postulated that colistin, like aminoglycoside antibiotics, may bind to secretory mucin in sputum or epithelial mucin that lines airways, reducing free drug levels. To test this hypothesis, we measured binding of colistin and other antibiotics to porcine mucin, a family of densely glycosylated proteins used as a surrogate for human sputum and airway mucin. Antibiotics were incubated in dialysis tubing with or without mucin, and concentrations of unbound antibiotics able to penetrate the dialysis tubing were measured over time using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The percentage of antibiotic measured in the dialysate after 4 h in the presence of mucin, relative to the amount without mucin, was 15% for colistin, 16% for polymyxin B, 19% for tobramycin, 52% for ciprofloxacin, and 78% for daptomycin. Antibiotics with the strongest mucin binding had an overall polybasic positive charge, whereas those with comparatively little binding were less basic. When comparing MICs measured with or without added mucin, colistin and polymyxin B showed >100-fold increases in MICs for multiple Gram-negative bacteria. Preclinical evaluation of mucin binding should become a standard procedure when considering the potential pulmonary use of new or existing antibiotics, particularly those with a polybasic overall charge. In the airways, mucin binding may reduce the antibacterial efficacy of inhaled or intravenously administered colistin, and the presence of sub-MIC effective antibiotic concentrations could result in the development of antibiotic resistance. PMID:26169405

  16. New binding mode to TNF-alpha revealed by ubiquitin-based artificial binding protein.

    Directory of Open Access Journals (Sweden)

    Andreas Hoffmann

    Full Text Available A variety of approaches have been employed to generate binding proteins from non-antibody scaffolds. Utilizing a beta-sheet of the human ubiquitin for paratope creation we obtained binding proteins against tumor necrosis factor (TNF-alpha. The bioactive form of this validated pharmacological target protein is a non-covalently linked homo-trimer. This structural feature leads to the observation of a certain heterogeneity concerning the binding mode of TNF-alpha binding molecules, for instance in terms of monomer/trimer specificity. We analyzed a ubiquitin-based TNF-alpha binder, selected by ribosome display, with a particular focus on its mode of interaction. Using enzyme-linked immunosorbent assays, specific binding to TNF-alpha with nanomolar affinity was observed. In isothermal titration calorimetry we obtained comparable results regarding the affinity and detected an exothermic reaction with one ubiquitin-derived binding molecule binding one TNF-alpha trimer. Using NMR spectroscopy and other analytical methods the 1:3 stoichiometry could be confirmed. Detailed binding analysis showed that the interaction is affected by the detergent Tween-20. Previously, this phenomenon was reported only for one other type of alternative scaffold-derived binding proteins--designed ankyrin repeat proteins--without further investigation. As demonstrated by size exclusion chromatography and NMR spectroscopy, the presence of the detergent increases the association rate significantly. Since the special architecture of TNF-alpha is known to be modulated by detergents, the access to the recognized epitope is indicated to be restricted by conformational transitions within the target protein. Our results suggest that the ubiquitin-derived binding protein targets a new epitope on TNF-alpha, which differs from the epitopes recognized by TNF-alpha neutralizing antibodies.

  17. Salt modulates the stability and lipid binding affinity of the adipocyte lipid-binding proteins

    Science.gov (United States)

    Schoeffler, Allyn J.; Ruiz, Carmen R.; Joubert, Allison M.; Yang, Xuemei; LiCata, Vince J.

    2003-01-01

    Adipocyte lipid-binding protein (ALBP or aP2) is an intracellular fatty acid-binding protein that is found in adipocytes and macrophages and binds a large variety of intracellular lipids with high affinity. Although intracellular lipids are frequently charged, biochemical studies of lipid-binding proteins and their interactions often focus most heavily on the hydrophobic aspects of these proteins and their interactions. In this study, we have characterized the effects of KCl on the stability and lipid binding properties of ALBP. We find that added salt dramatically stabilizes ALBP, increasing its Delta G of unfolding by 3-5 kcal/mol. At 37 degrees C salt can more than double the stability of the protein. At the same time, salt inhibits the binding of the fluorescent lipid 1-anilinonaphthalene-8-sulfonate (ANS) to the protein and induces direct displacement of the lipid from the protein. Thermodynamic linkage analysis of the salt inhibition of ANS binding shows a nearly 1:1 reciprocal linkage: i.e. one ion is released from ALBP when ANS binds, and vice versa. Kinetic experiments show that salt reduces the rate of association between ANS and ALBP while simultaneously increasing the dissociation rate of ANS from the protein. We depict and discuss the thermodynamic linkages among stability, lipid binding, and salt effects for ALBP, including the use of these linkages to calculate the affinity of ANS for the denatured state of ALBP and its dependence on salt concentration. We also discuss the potential molecular origins and potential intracellular consequences of the demonstrated salt linkages to stability and lipid binding in ALBP.

  18. Ubiquitin-binding proteins: similar, but different

    DEFF Research Database (Denmark)

    Andersen, Katrine M; Hofmann, Kay; Hartmann-Petersen, Rasmus

    2005-01-01

    and phosphatases, specific sets of ubiquitinating/deubiquitinating enzymes control the degree of ubiquitination. A large number of ubiquitin-binding proteins act at different steps in the downstream pathways, followed by the ubiquitinated protein. Different families of ubiquitin-binding proteins have been...... described. UBA (ubiquitin-associated) domain-containing proteins is the largest family and includes members involved in different cell processes. The smaller groups of UIM (ubiquitin-interacting motif), GAT [GGA (Golgi-associated gamma-adaptin homologous) and Tom1 (target of Myb 1)], CUE (coupling...

  19. Binding energy of two-dimensional biexcitons

    DEFF Research Database (Denmark)

    Singh, Jai; Birkedal, Dan; Vadim, Lyssenko

    1996-01-01

    Using a model structure for a two-dimensional (2D) biexciton confined in a quantum well, it is shown that the form of the Hamiltonian of the 2D biexciton reduces into that of an exciton. The binding energies and Bohr radii of a 2D biexciton in its various internal energy states are derived...... analytically using the fractional dimension approach. The ratio of the binding energy of a 2D biexciton to that of a 2D exciton is found to be 0.228, which agrees very well with the recent experimental value. The results of our approach are compared with those of earlier theories....

  20. Binding energies of hypernuclei and hypernuclear interactions

    Energy Technology Data Exchange (ETDEWEB)

    Bodmer, A.R. [Argonne National Lab., IL (United States)]|[Univ. of Illinois, Chicago, IL (United States). Dept. of Physics; Murali, S.; Usmani, Q.N. [Jamia Millia Islamia, New Delhi (India). Dept. of Physics

    1996-05-01

    In part 1 the effect of nuclear core dynamics on the binding energies of {Lambda} hypernuclei is discussed in the framework of variational correlated wave functions. In particular, the authors discuss a new rearrangement energy contribution and its effect on the core polarization. In part 2 they consider the interpretation of the {Lambda} single-particle energy in terms of basic {Lambda}-nuclear interactions using a local density approximation based on a Fermi hypernetted chain calculation of the A binding to nuclear matter. To account for the data strongly repulsive 3-body {Lambda}NN forces are required. Also in this framework they discuss core polarization for medium and heavier hypernuclei.

  1. Binding energies of hypernuclei and hypernuclear interactions

    International Nuclear Information System (INIS)

    Bodmer, A.R.; Univ. of Illinois, Chicago, IL; Murali, S.; Usmani, Q.N.

    1996-01-01

    In part 1 the effect of nuclear core dynamics on the binding energies of Λ hypernuclei is discussed in the framework of variational correlated wave functions. In particular, the authors discuss a new rearrangement energy contribution and its effect on the core polarization. In part 2 they consider the interpretation of the Λ single-particle energy in terms of basic Λ-nuclear interactions using a local density approximation based on a Fermi hypernetted chain calculation of the A binding to nuclear matter. To account for the data strongly repulsive 3-body ΛNN forces are required. Also in this framework they discuss core polarization for medium and heavier hypernuclei

  2. Differences in oestrogen receptors in malignant and normal breast tissue as identified by the binding of a new synthetic progestogen.

    Science.gov (United States)

    Iqbal, M. J.; Colletta, A. A.; Houmayoun-Valyani, S. D.; Baum, M.

    1986-01-01

    Oestrogen receptor protein (ER) was detected in 9 of 11 samples of malignant breast tissue and 8 of 9 samples of normal breast tissue. Levels of cytosolic ER (ERc) in malignant breast were 21-1102 fmol mg-1 soluble protein (Kd 1.8 X 10(-9)-3.1 X 10(-8) mol l-1) and those of nucleosolic ER (ERn), 13-526 fmol mg-1 soluble protein (Kd 2.1 X 10(-9)-1.4 X 10(-8) mol l-1). In normal breast tissue ERc levels were 33-640 fmol mg-1 soluble protein (Kd 1.3 X 10(-10)-3.2 X 10(-9) mol l-1), ERn was detected in only 2 samples, 8 and 87 fmol mg-1 soluble protein with Kd 3.2 X 10(-9) and 1.4 X 10(-9) l mol-1 respectively. 17 alpha-ethinyl-13 beta-ethyl-17 beta-hydroxy-4,15-gonadiene-3-one (gestodene), a new synthetic progestogen displaced 3H-oestradiol (3H-E2) from both ERc and ERn in malignant tissue but not in normal breast, or these receptors from endometrial tissue. In competition studies gestodene was approximately 3 times more effective in displacing 3H-E2 from ERc and ERn in malignant breast tissue than the natural ligand. Quantitation of ER by gestodene were ERc, 12-1134 fmol gestodene bound mg-1 soluble protein (Kd 1 X 10(-9)-8.1 X 10(-9) mol l-1); ERn, 17-531 fmol gestodene bound mg-1 soluble protein (Kd 1.6 X 10(-9)-1.1 X 10(-8) mol l-1). L-13-ethyl-17 alpha-ethinyl, 17 beta-hydroxy-gonen-3-one (levonorgestrel) showed no binding to ER in malignant breast, normal breast or endometrial tissue. In circulation both gestodene and levonorgestrel displaced E2 from sex hormone binding globulin more than any of the androgens tested. These results suggest that gestodene is a progestogen with oestrogenic and/or antioestrogenic properties and provide strong evidence for differences in ER from malignant and normal breast tissue. PMID:3756080

  3. Myeloperoxidase Selectively Binds and Selectively Kills Microbes ▿ †

    OpenAIRE

    Allen, Robert C.; Stephens, Jackson T.

    2010-01-01

    Myeloperoxidase (MPO) is reported to selectively bind to bacteria. The present study provides direct evidence of MPO binding selectivity and tests the relationship of selective binding to selective killing. The microbicidal effectiveness of H2O2 and of OCl− was compared to that of MPO plus H2O2. Synergistic microbicidal action was investigated by combining Streptococcus sanguinis, a H2O2-producing microbe showing low MPO binding, with high-MPO-binding Escherichia coli, Staphylococcus aureus, ...

  4. Studies on folate binding and a radioassay for serum and whole blood folate using goat milk as binding agent

    International Nuclear Information System (INIS)

    Piyasena, R.D.; Weerasekera, D.A.; Hettiaratchi, N.; Wikramanayake, T.W.; Sri Lanka Univ., Peradeniya Campus. Nuclear Medicine Unit)

    1977-01-01

    Preparations of cow, goat, buffalo, and human milk in addition to pig plasma were tested for folate binding properties. Of these, only pig plasma and goat milk showed sufficient binding to enable use as binding agents in a radioassay for serum and whole blood folate. The binding of folate by cow mild preparations in particular was found to be very poor. (orig.) [de

  5. Characterizing low affinity epibatidine binding to α4β2 nicotinic acetylcholine receptors with ligand depletion and nonspecific binding

    Directory of Open Access Journals (Sweden)

    Person Alexandra M

    2011-11-01

    Full Text Available Abstract Background Along with high affinity binding of epibatidine (Kd1≈10 pM to α4β2 nicotinic acetylcholine receptor (nAChR, low affinity binding of epibatidine (Kd2≈1-10 nM to an independent binding site has been reported. Studying this low affinity binding is important because it might contribute understanding about the structure and synthesis of α4β2 nAChR. The binding behavior of epibatidine and α4β2 AChR raises a question about interpreting binding data from two independent sites with ligand depletion and nonspecific binding, both of which can affect equilibrium binding of [3H]epibatidine and α4β2 nAChR. If modeled incorrectly, ligand depletion and nonspecific binding lead to inaccurate estimates of binding constants. Fitting total equilibrium binding as a function of total ligand accurately characterizes a single site with ligand depletion and nonspecific binding. The goal of this study was to determine whether this approach is sufficient with two independent high and low affinity sites. Results Computer simulations of binding revealed complexities beyond fitting total binding for characterizing the second, low affinity site of α4β2 nAChR. First, distinguishing low-affinity specific binding from nonspecific binding was a potential problem with saturation data. Varying the maximum concentration of [3H]epibatidine, simultaneously fitting independently measured nonspecific binding, and varying α4β2 nAChR concentration were effective remedies. Second, ligand depletion helped identify the low affinity site when nonspecific binding was significant in saturation or competition data, contrary to a common belief that ligand depletion always is detrimental. Third, measuring nonspecific binding without α4β2 nAChR distinguished better between nonspecific binding and low-affinity specific binding under some circumstances of competitive binding than did presuming nonspecific binding to be residual [3H]epibatidine binding after

  6. Binding sites analyser (BiSA: software for genomic binding sites archiving and overlap analysis.

    Directory of Open Access Journals (Sweden)

    Matloob Khushi

    Full Text Available Genome-wide mapping of transcription factor binding and histone modification reveals complex patterns of interactions. Identifying overlaps in binding patterns by different factors is a major objective of genomic studies, but existing methods to archive large numbers of datasets in a personalised database lack sophistication and utility. Therefore we have developed transcription factor DNA binding site analyser software (BiSA, for archiving of binding regions and easy identification of overlap with or proximity to other regions of interest. Analysis results can be restricted by chromosome or base pair overlap between regions or maximum distance between binding peaks. BiSA is capable of reporting overlapping regions that share common base pairs; regions that are nearby; regions that are not overlapping; and average region sizes. BiSA can identify genes located near binding regions of interest, genomic features near a gene or locus of interest and statistical significance of overlapping regions can also be reported. Overlapping results can be visualized as Venn diagrams. A major strength of BiSA is that it is supported by a comprehensive database of publicly available transcription factor binding sites and histone modifications, which can be directly compared to user data. The documentation and source code are available on http://bisa.sourceforge.net.

  7. RBPmap: a web server for mapping binding sites of RNA-binding proteins.

    Science.gov (United States)

    Paz, Inbal; Kosti, Idit; Ares, Manuel; Cline, Melissa; Mandel-Gutfreund, Yael

    2014-07-01

    Regulation of gene expression is executed in many cases by RNA-binding proteins (RBPs) that bind to mRNAs as well as to non-coding RNAs. RBPs recognize their RNA target via specific binding sites on the RNA. Predicting the binding sites of RBPs is known to be a major challenge. We present a new webserver, RBPmap, freely accessible through the website http://rbpmap.technion.ac.il/ for accurate prediction and mapping of RBP binding sites. RBPmap has been developed specifically for mapping RBPs in human, mouse and Drosophila melanogaster genomes, though it supports other organisms too. RBPmap enables the users to select motifs from a large database of experimentally defined motifs. In addition, users can provide any motif of interest, given as either a consensus or a PSSM. The algorithm for mapping the motifs is based on a Weighted-Rank approach, which considers the clustering propensity of the binding sites and the overall tendency of regulatory regions to be conserved. In addition, RBPmap incorporates a position-specific background model, designed uniquely for different genomic regions, such as splice sites, 5' and 3' UTRs, non-coding RNA and intergenic regions. RBPmap was tested on high-throughput RNA-binding experiments and was proved to be highly accurate. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. ALG-2, a multifunctional calcium binding protein?

    DEFF Research Database (Denmark)

    Tarabykina, Svetlana; Mollerup, Jens; Winding Gojkovic, P.

    2004-01-01

    ALG-2 was originally discovered as a pro-apoptotic protein in a genetic screen. Due to its ability to bind calcium with high affinity it was postulated to provide a link between the known effect of calcium in programmed cell death and the molecular death execution machinery. This review article d...

  9. Tension-induced binding of semiflexible biopolymers

    International Nuclear Information System (INIS)

    Benetatos, Panayotis; Heydt, Alice von der; Zippelius, Annette

    2014-01-01

    We investigate theoretically the effect of polymer tension on the collective behavior of reversibly binding cross-links. For this purpose, we employ a model of two weakly bending wormlike chains aligned in parallel by a tensile force, with a sequence of inter-chain binding sites regularly spaced along the contours. Reversible cross-links attach and detach at the sites with an affinity controlled by a chemical potential. In a mean-field approach, we calculate the free energy of the system and find the emergence of a free-energy barrier which controls the reversible (un)binding. The tension affects the conformational entropy of the chains which competes with the binding energy of the cross-links. This competition gives rise to a sudden increase in the fraction of bound sites as the tension increases. We show that this transition is related to the cross-over between weak and strong localization of a directed polymer in a pinning potential. The cross-over to the strongly bound state can be interpreted as a mechanism for force-stiffening which exceeds the capabilities of single-chain elasticity and thus available only to reversibly cross-linked polymers. (paper)

  10. Cross-Modal Binding in Developmental Dyslexia

    Science.gov (United States)

    Jones, Manon W.; Branigan, Holly P.; Parra, Mario A.; Logie, Robert H.

    2013-01-01

    The ability to learn visual-phonological associations is a unique predictor of word reading, and individuals with developmental dyslexia show impaired ability in learning these associations. In this study, we compared developmentally dyslexic and nondyslexic adults on their ability to form cross-modal associations (or "bindings") based…

  11. Telomere-binding proteins of Arabidopsis thaliana.

    Science.gov (United States)

    Zentgraf, U

    1995-02-01

    The nucleoprotein structure of Arabidopsis thaliana telomeres was investigated. A protein specifically binding to telomeric sequences was characterized by gel mobility shift assays with synthetic oligonucleotides consisting of four 7 bp telomeric repeats of Arabidopsis (TTTAGGG) and crude nuclear protein extracts of Arabidopsis leaves. These DNA-protein binding studies revealed that the binding affinity of this telomere-binding protein to the G-rich single-strand as well as to the double-stranded telomeric DNA is much higher than to the C-rich single-strand. The molecular mass of the protein was identified by SDS-PAGE to be 67 kDa. The isoelectric points were determined to be 5.0, 4.85 and 4.7, respectively, indicating that either one protein with different modifications or three slightly different proteins have been isolated. An RNA component, possibly serving as a template for reverse transcription of a plant telomerase, does not mediate the DNA-protein contact because the DNA-protein interactions were not RNAse-sensitive.

  12. Binding of cationic surfactants to humic substances

    NARCIS (Netherlands)

    Ishiguro, M.; Tan, W.; Koopal, L.K.

    2007-01-01

    Commercial surfactants are introduced into the environment either through waste products or site-specific contamination. The amphiphilic nature of both surfactants and humic substances (HS) leads to their mutual attraction especially when surfactant and HS are oppositely charged. Binding of the

  13. Ribosome binding site recognition using neural networks

    Directory of Open Access Journals (Sweden)

    Márcio Ferreira da Silva Oliveira

    2004-01-01

    Full Text Available Pattern recognition is an important process for gene localization in genomes. The ribosome binding sites are signals that can help in the identification of a gene. It is difficult to find these signals in the genome through conventional methods because they are highly degenerated. Artificial Neural Networks is the approach used in this work to address this problem.

  14. tPA-binding RNA Aptamers

    DEFF Research Database (Denmark)

    Bjerregaard, Nils

    2015-01-01

    -density lipoprotein receptor Related Protein-1 (LRP-1). Here, we describe the selection and characterisation of structured RNA ligands (“RNA aptamers”) to tPA, K18 and K32. Both aptamers were truncated to minimal 32-nucleotide constructs (v2) with improved or unchanged activities, and were shown to bind tPA with low...

  15. Non-binding relationship between visual features

    Directory of Open Access Journals (Sweden)

    Dragan eRangelov

    2014-10-01

    Full Text Available The answer as to how visual attributes processed in different brain loci at different speeds are bound together to give us our unitary experience of the visual world remains unknown. In this study we investigated whether bound representations arise, as commonly assumed, through physiological interactions between cells in the visual areas. In a focal attentional task in which correct responses from either bound or unbound representations were possible, participants discriminated the colour or orientation of briefly presented single bars. On the assumption that representations of the two attributes are bound, the accuracy of reporting the colour and orientation should co-vary. By contrast, if the attributes are not mandatorily bound, the accuracy of reporting the two attributes should be independent. The results of our psychophysical studies reported here supported the latter, non-binding, relationship between visual features, suggesting that binding does not necessarily occur even under focal attention. We propose a task-contingent binding mechanism, postulating that binding occurs at late, post-perceptual, stages through the intervention of memory.

  16. Nucleotide binding to Na+/K+-ATPase

    Czech Academy of Sciences Publication Activity Database

    Kubala, Martin; Lánský, Zdeněk; Ettrich, R.; Plášek, J.; Teisinger, Jan; Amler, Evžen

    2005-01-01

    Roč. 272, č. S1 (2005), s. 191-191 E-ISSN 1742-4658. [FEBS Congress /30./ and IUBMB Conference /9./. 02.07.2005-07.07.2005, Budapest] Keywords : Na+/K+- ATPase * ATP binding * TNP-ATP Subject RIV: BO - Biophysics

  17. The Double Bind: The next Generation

    Science.gov (United States)

    Malcom, Lindsey E.; Malcom, Shirley M.

    2011-01-01

    In this foreword, Shirley Malcom and Lindsey Malcom speak to the history and current status of women of color in science, technology, engineering, and mathematics (STEM) fields. As the author of the seminal report "The Double Bind: The Price of Being a Minority Woman in Science", Shirley Malcom is uniquely poised to give us an insightful…

  18. 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 (Ptannin (HT) level (Ptannin 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 (Ptannin 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.

  19. Alkali binding in hydrated Portland cement paste

    NARCIS (Netherlands)

    Chen, Wei; Brouwers, Jos

    2010-01-01

    The alkali-binding capacity of C–S–H in hydrated Portland cement pastes is addressed in this study. The amount of bound alkalis in C–S–H is computed based on the alkali partition theories firstly proposed by Taylor (1987) and later further developed by Brouwers and Van Eijk (2003). Experimental data

  20. Retinoblastoma-binding protein 1 has an interdigitated double Tudor domain with DNA binding activity.

    Science.gov (United States)

    Gong, Weibin; Wang, Jinfeng; Perrett, Sarah; Feng, Yingang

    2014-02-21

    Retinoblastoma-binding protein 1 (RBBP1) is a tumor and leukemia suppressor that binds both methylated histone tails and DNA. Our previous studies indicated that RBBP1 possesses a Tudor domain, which cannot bind histone marks. In order to clarify the function of the Tudor domain, the solution structure of the RBBP1 Tudor domain was determined by NMR and is presented here. Although the proteins are unrelated, the RBBP1 Tudor domain forms an interdigitated double Tudor structure similar to the Tudor domain of JMJD2A, which is an epigenetic mark reader. This indicates the functional diversity of Tudor domains. The RBBP1 Tudor domain structure has a significant area of positively charged surface, which reveals a capability of the RBBP1 Tudor domain to bind nucleic acids. NMR titration and isothermal titration calorimetry experiments indicate that the RBBP1 Tudor domain binds both double- and single-stranded DNA with an affinity of 10-100 μM; no apparent DNA sequence specificity was detected. The DNA binding mode and key interaction residues were analyzed in detail based on a model structure of the Tudor domain-dsDNA complex, built by HADDOCK docking using the NMR data. Electrostatic interactions mediate the binding of the Tudor domain with DNA, which is consistent with NMR experiments performed at high salt concentration. The DNA-binding residues are conserved in Tudor domains of the RBBP1 protein family, resulting in conservation of the DNA-binding function in the RBBP1 Tudor domains. Our results provide further insights into the structure and function of RBBP1.

  1. Five of Five VHHs Neutralizing Poliovirus Bind the Receptor-Binding Site.

    Science.gov (United States)

    Strauss, Mike; Schotte, Lise; Thys, Bert; Filman, David J; Hogle, James M

    2016-01-13

    Nanobodies, or VHHs, that recognize poliovirus type 1 have previously been selected and characterized as candidates for antiviral agents or reagents for standardization of vaccine quality control. In this study, we present high-resolution cryo-electron microscopy reconstructions of poliovirus with five neutralizing VHHs. All VHHs bind the capsid in the canyon at sites that extensively overlap the poliovirus receptor-binding site. In contrast, the interaction involves a unique (and surprisingly extensive) surface for each of the five VHHs. Five regions of the capsid were found to participate in binding with all five VHHs. Four of these five regions are known to alter during the expansion of the capsid associated with viral entry. Interestingly, binding of one of the VHHs, PVSS21E, resulted in significant changes of the capsid structure and thus seems to trap the virus in an early stage of expansion. We describe the cryo-electron microscopy structures of complexes of five neutralizing VHHs with the Mahoney strain of type 1 poliovirus at resolutions ranging from 3.8 to 6.3Å. All five VHHs bind deep in the virus canyon at similar sites that overlap extensively with the binding site for the receptor (CD155). The binding surfaces on the VHHs are surprisingly extensive, but despite the use of similar binding surfaces on the virus, the binding surface on the VHHs is unique for each VHH. In four of the five complexes, the virus remains essentially unchanged, but for the fifth there are significant changes reminiscent of but smaller in magnitude than the changes associated with cell entry, suggesting that this VHH traps the virus in a previously undescribed early intermediate state. The neutralizing mechanisms of the VHHs and their potential use as quality control agents for the end game of poliovirus eradication are discussed. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Binding site graphs: a new graph theoretical framework for prediction of transcription factor binding sites.

    Directory of Open Access Journals (Sweden)

    Timothy E Reddy

    2007-05-01

    Full Text Available Computational prediction of nucleotide binding specificity for transcription factors remains a fundamental and largely unsolved problem. Determination of binding positions is a prerequisite for research in gene regulation, a major mechanism controlling phenotypic diversity. Furthermore, an accurate determination of binding specificities from high-throughput data sources is necessary to realize the full potential of systems biology. Unfortunately, recently performed independent evaluation showed that more than half the predictions from most widely used algorithms are false. We introduce a graph-theoretical framework to describe local sequence similarity as the pair-wise distances between nucleotides in promoter sequences, and hypothesize that densely connected subgraphs are indicative of transcription factor binding sites. Using a well-established sampling algorithm coupled with simple clustering and scoring schemes, we identify sets of closely related nucleotides and test those for known TF binding activity. Using an independent benchmark, we find our algorithm predicts yeast binding motifs considerably better than currently available techniques and without manual curation. Importantly, we reduce the number of false positive predictions in yeast to less than 30%. We also develop a framework to evaluate the statistical significance of our motif predictions. We show that our approach is robust to the choice of input promoters, and thus can be used in the context of predicting binding positions from noisy experimental data. We apply our method to identify binding sites using data from genome scale ChIP-chip experiments. Results from these experiments are publicly available at http://cagt10.bu.edu/BSG. The graphical framework developed here may be useful when combining predictions from numerous computational and experimental measures. Finally, we discuss how our algorithm can be used to improve the sensitivity of computational predictions of

  3. Predicting binding within disordered protein regions to structurally characterised peptide-binding domains.

    Directory of Open Access Journals (Sweden)

    Waqasuddin Khan

    Full Text Available Disordered regions of proteins often bind to structured domains, mediating interactions within and between proteins. However, it is difficult to identify a priori the short disordered regions involved in binding. We set out to determine if docking such peptide regions to peptide binding domains would assist in these predictions.We assembled a redundancy reduced dataset of SLiM (Short Linear Motif containing proteins from the ELM database. We selected 84 sequences which had an associated PDB structures showing the SLiM bound to a protein receptor, where the SLiM was found within a 50 residue region of the protein sequence which was predicted to be disordered. First, we investigated the Vina docking scores of overlapping tripeptides from the 50 residue SLiM containing disordered regions of the protein sequence to the corresponding PDB domain. We found only weak discrimination of docking scores between peptides involved in binding and adjacent non-binding peptides in this context (AUC 0.58.Next, we trained a bidirectional recurrent neural network (BRNN using as input the protein sequence, predicted secondary structure, Vina docking score and predicted disorder score. The results were very promising (AUC 0.72 showing that multiple sources of information can be combined to produce results which are clearly superior to any single source.We conclude that the Vina docking score alone has only modest power to define the location of a peptide within a larger protein region known to contain it. However, combining this information with other knowledge (using machine learning methods clearly improves the identification of peptide binding regions within a protein sequence. This approach combining docking with machine learning is primarily a predictor of binding to peptide-binding sites, and is not intended as a predictor of specificity of binding to particular receptors.

  4. The Tomato Nucleotide-binding Leucine-rich Repeat (NLR) Immune Receptor I-2 Couples DNA-Binding to Nucleotide-Binding Domain Nucleotide Exchange

    NARCIS (Netherlands)

    Fenyk, S.; Dixon, C.H.; Gittens, W.H.; Townsend, P.D.; Sharples, G.J.; Pålsson, L.O.; Takken, F.L.W.; Cann, M.J.

    2016-01-01

    Plant nucleotide-binding leucine-rich repeat (NLR) proteins enable plants to recognise and respond to pathogen attack. Previously, we demonstrated that the Rx1 NLR of potato is able to bind and bend DNA in vitro. DNA binding in situ requires its genuine activation following pathogen perception.

  5. Li+-ligand binding energies and the effect of ligand fluorination on the binding energies

    Science.gov (United States)

    Bauschlicher, Charles W.

    2018-02-01

    The Li+-ligand binding energies are computed for seven ligands and their perfluoro analogs using Density Functional Theory. The bonding is mostly electrostatic in origin. Thus the size of the binding energy tends to correlate with the ligand dipole moment, however, the charge-induced dipole contribution can be sufficiently large to affect the dipole-binding energy correlation. The perfluoro species are significantly less strongly bound than their parents, because the electron withdrawing power of the fluorine reduces the ligand dipole moment.

  6. Chromate Binding and Removal by the Molybdate-Binding Protein ModA.

    Science.gov (United States)

    Karpus, Jason; Bosscher, Michael; Ajiboye, Ifedayo; Zhang, Liang; He, Chuan

    2017-04-04

    Effective and cheap methods and techniques for the safe removal of hexavalent chromate from the environment are in increasingly high demand. High concentrations of hexavalent chromate have been shown to have numerous harmful effects on human biology. We show that the E. coli molybdate-binding protein ModA is a genetically encoded tool capable of removing chromate from aqueous solutions. Although previously reported to not bind chromate, we show that ModA binds chromate tightly and is capable of removing chromate to levels well below current US federal standards. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Rate Constants and Mechanisms of Protein-Ligand Binding.

    Science.gov (United States)

    Pang, Xiaodong; Zhou, Huan-Xiang

    2017-05-22

    Whereas protein-ligand binding affinities have long-established prominence, binding rate constants and binding mechanisms have gained increasing attention in recent years. Both new computational methods and new experimental techniques have been developed to characterize the latter properties. It is now realized that binding mechanisms, like binding rate constants, can and should be quantitatively determined. In this review, we summarize studies and synthesize ideas on several topics in the hope of providing a coherent picture of and physical insight into binding kinetics. The topics include microscopic formulation of the kinetic problem and its reduction to simple rate equations; computation of binding rate constants; quantitative determination of binding mechanisms; and elucidation of physical factors that control binding rate constants and mechanisms.

  8. Cue integration and the perception of action in intentional binding

    DEFF Research Database (Denmark)

    Wolpe, Noham; Haggard, Patrick; Siebner, Hartwig R

    2013-01-01

    , further analyses showed that cue integration accounted for changes in action binding, but not tone binding. These findings establish a role for cue integration in action binding and support the growing evidence suggesting that action and tone binding are, at least in part, driven by distinct mechanisms....... that binding results from cue integration, in which a voluntary action provides information about the timing of its consequences or vice versa. The perception of the timing of either event is then a weighted average, determined according to the reliability of each of these two cues. Here we tested...... the contribution of cue integration to the perception of action and its sensory effect in binding, that is, action and tone binding, by manipulating the sensory reliability of the outcome tone. As predicted, when tone reliability was reduced, action binding was diminished and tone binding was increased. However...

  9. Maternal social stress during late pregnancy affects hypothalamic-pituitary-adrenal function and brain neurotransmitter systems in pig offspring.

    Science.gov (United States)

    Otten, W; Kanitz, E; Couret, D; Veissier, I; Prunier, A; Merlot, E

    2010-04-01

    Maternal stress in pregnant sows may induce long-lasting alterations in the behavior, physiology, and immunity of their offspring. The aim of the present study was to investigate the consequences of repeated social stress during late gestation on determinants of the hypothalamic-pituitary-adrenal axis and on hippocampal neurotransmitter profiles in pig offspring. All pregnant gilts were housed in pairs. Each Stress gilt was mixed with an unfamiliar gilt twice a week between days 77 and 105 of gestation (n=18). Control gilts were housed in stable pairs over the same period (n=18). Plasma cortisol and corticosteroid binding globulin (CBG) were measured in 1 male and 1 female per litter in a basal situation on postnatal days (PND) 4, 26, and 60 and in a stressful situation at PND 28 (2 d after weaning) and 62 (2 d after relocation to a new building). Prenatal stress had no effect on plasma cortisol, but it decreased CBG at PND 26. Brain and adrenals were collected from 1 female per litter after weaning or relocation at PND 28 and PND 62. Adrenals were additionally collected at PND 4. Glucocorticoid receptor binding in the hippocampus and hypothalamus was not affected by prenatal treatment. However, prenatal stress increased the expression of 11beta-hydroxysteroid dehydrogenase type 1 mRNA in the hippocampus after weaning (P<0.05) and after relocation (P=0.08). In addition, prenatally stressed piglets showed an increased 5-hydroxyindole-3-acetic acid to 5-hydroxytryptamine ratio in the hippocampus after weaning and increased hippocampal c-fos mRNA expression and noradrenaline concentration after relocation (P<0.05). Prenatal stress also increased the relative adrenal weight at PND 4 and the cell density in the cortex and the medulla at PND 28, whereas no difference was found for activities of catecholamine-synthesising enzymes in the medulla. Overall, our data indicate that repeated social stress during pregnancy has long-lasting consequences on hypothalamic

  10. The inhibition of anti-DNA binding to DNA by nucleic acid binding polymers.

    Directory of Open Access Journals (Sweden)

    Nancy A Stearns

    Full Text Available Antibodies to DNA (anti-DNA are the serological hallmark of systemic lupus erythematosus (SLE and can mediate disease pathogenesis by the formation of immune complexes. Since blocking immune complex formation can attenuate disease manifestations, the effects of nucleic acid binding polymers (NABPs on anti-DNA binding in vitro were investigated. The compounds tested included polyamidoamine dendrimer, 1,4-diaminobutane core, generation 3.0 (PAMAM-G3, hexadimethrine bromide, and a β-cylodextrin-containing polycation. As shown with plasma from patients with SLE, NABPs can inhibit anti-DNA antibody binding in ELISA assays. The inhibition was specific since the NABPs did not affect binding to tetanus toxoid or the Sm protein, another lupus autoantigen. Furthermore, the polymers could displace antibody from preformed complexes. Together, these results indicate that NABPs can inhibit the formation of immune complexes and may represent a new approach to treatment.

  11. Relating the shape of protein binding sites to binding affinity profiles: is there an association?

    Directory of Open Access Journals (Sweden)

    Bitter István

    2010-10-01

    Full Text Available Abstract Background Various pattern-based methods exist that use in vitro or in silico affinity profiles for classification and functional examination of proteins. Nevertheless, the connection between the protein affinity profiles and the structural characteristics of the binding sites is still unclear. Our aim was to investigate the association between virtual drug screening results (calculated binding free energy values and the geometry of protein binding sites. Molecular Affinity Fingerprints (MAFs were determined for 154 proteins based on their molecular docking energy results for 1,255 FDA-approved drugs. Protein binding site geometries were characterized by 420 PocketPicker descriptors. The basic underlying component structure of MAFs and binding site geometries, respectively, were examined by principal component analysis; association between principal components extracted from these two sets of variables was then investigated by canonical correlation and redundancy analyses. Results PCA analysis of the MAF variables provided 30 factors which explained 71.4% of the total variance of the energy values while 13 factors were obtained from the PocketPicker descriptors which cumulatively explained 94.1% of the total variance. Canonical correlation analysis resulted in 3 statistically significant canonical factor pairs with correlation values of 0.87, 0.84 and 0.77, respectively. Redundancy analysis indicated that PocketPicker descriptor factors explain 6.9% of the variance of the MAF factor set while MAF factors explain 15.9% of the total variance of PocketPicker descriptor factors. Based on the salient structures of the factor pairs, we identified a clear-cut association between the shape and bulkiness of the drug molecules and the protein binding site descriptors. Conclusions This is the first study to investigate complex multivariate associations between affinity profiles and the geometric properties of protein binding sites. We found that

  12. Ail Binding to Fibronectin Facilitates Yersinia pestis Binding to Host Cells and Yop Delivery▿

    OpenAIRE

    Tsang, Tiffany M.; Felek, Suleyman; Krukonis, Eric S.

    2010-01-01

    Yersinia pestis, the causative agent of plague, evades host immune responses and rapidly causes disease. The Y. pestis adhesin Ail mediates host cell binding and is critical for Yop delivery. To identify the Ail receptor(s), Ail was purified following overexpression in Escherichia coli. Ail bound specifically to fibronectin, an extracellular matrix protein with the potential to act as a bridge between Ail and host cells. Ail expressed by E. coli also mediated binding to purified fibronectin, ...

  13. Is there a link between selectivity and binding thermodynamics profiles?

    Science.gov (United States)

    Tarcsay, Ákos; Keserű, György M

    2015-01-01

    Thermodynamics of ligand binding is influenced by the interplay between enthalpy and entropy contributions of the binding event. The impact of these binding free energy components, however, is not limited to the primary target only. Here, we investigate the relationship between binding thermodynamics and selectivity profiles by combining publicly available data from broad off-target assay profiling and the corresponding thermodynamics measurements. Our analysis indicates that compounds binding their primary targets with higher entropy contributions tend to hit more off-targets compared with those ligands that demonstrated enthalpy-driven binding. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Cobalamin and its binding protein in rat milk

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Nexø, Ebba; Poulsen, Steen Seier

    1989-01-01

    Cobalamin and its binding protein, haptocorrin, are present in rat milk throughout the lactation period. The concentration of cobalamin is approximately 0.3-times the concentration of the unsaturated binding protein. The concentration of the unsaturated cobalamin-binding protein varies between 18...... nmol l-1 and 16 nmol l-1. The binding protein has a Stokes radius of 2.49 nm when saturated with cobalamin and 2.61 nm when unsaturated. It binds cobalamin over a broad range of pH and is able to bind cobinamide also. With immunohistochemistry, we find haptocorrin immunoreactivity in the mammary glands...

  15. Effect of cobratoxin binding on the normal mode vibration within acetylcholine binding protein.

    Science.gov (United States)

    Bertaccini, Edward J; Lindahl, Erik; Sixma, Titia; Trudell, James R

    2008-04-01

    Recent crystal structures of the acetylcholine binding protein (AChBP) have revealed surprisingly small structural alterations upon ligand binding. Here we investigate the extent to which ligand binding may affect receptor dynamics. AChBP is a homologue of the extracellular component of ligand-gated ion channels (LGICs). We have previously used an elastic network normal-mode analysis to propose a gating mechanism for the LGICs and to suggest the effects of various ligands on such motions. However, the difficulties with elastic network methods lie in their inability to account for the modest effects of a small ligand or mutation on ion channel motion. Here, we report the successful application of an elastic network normal mode technique to measure the effects of large ligand binding on receptor dynamics. The present calculations demonstrate a clear alteration in the native symmetric motions of a protein due to the presence of large protein cobratoxin ligands. In particular, normal-mode analysis revealed that cobratoxin binding to this protein significantly dampened the axially symmetric motion of the AChBP that may be associated with channel gating in the full nAChR. The results suggest that alterations in receptor dynamics could be a general feature of ligand binding.

  16. Differential binding of heavy chain variable domain 3 antigen binding fragments to protein A chromatography resins.

    Science.gov (United States)

    Bach, Julia; Lewis, Nathaniel; Maggiora, Kathy; Gillespie, Alison J; Connell-Crowley, Lisa

    2015-08-28

    This work examines the binding of 15 different VH3 IgGs and their corresponding F(ab')2 fragments to two different protein A chromatography resins: MabSelect(®), which utilizes a recombinant protein A ligand, and MabSelect SuRe(®) (SuRe), which utilizes a tetrameric Z domain ligand. The results show that VH3 F(ab')2 fragments can exhibit a variety of binding behaviours for the two resins. Contrary to previously published data, a subset of these molecules show strong interaction with the Z domain of SuRe(®). Furthermore, the results show that sequence variability of residue 57 in the VH3 heavy chain CDR2 domain correlates with binding behaviour on MabSelect(®) and SuRe(®). Site-directed mutagenesis of this residue confers gain or loss of VH3 F(ab')2 binding to these resins in 3 mAbs, demonstrating that it plays a key role in both recombinant protein A and Z domain interaction. A fourth mAb with a longer CDR2 loop was not affected by mutation of residue 57, indicating that CDR2 domain length may alter the binding interface and lead to the involvement of other residues in protein A binding. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Fucosyl neoglycoprotein binds to mouse epididymal spermatozoa and inhibits sperm binding to the egg zona pellucida.

    Science.gov (United States)

    Oh, Y S; Ahn, H S; Gye, M C

    2013-12-01

    Glycan epitopes of cellular glycoconjugates act as versatile biochemical signals, and this sugar coding plays an important role in cell-to-cell recognition processes. In this study, our aims were to determine the distribution of sperm receptors with activity for fucosyl- and galactosyl glycans and to address whether monosugar neoglycoproteins functionally mimic the binding between zona pellucida (ZP) glycoproteins and spermatozoa. In mouse epididymal spermatozoa with intact acrosomes, fucopyranosyl bovine serum albumin (BSA-Fuc) bound to the segment of the acrosome, the equatorial segment, and the postacrosome region of the sperm head. Galactosyl BSA (BSA-Gal) binding activity was similar to that of BSA-Fuc, but was weaker. In acrosome-reacted spermatozoa treated with the Ca(2+) ionophore A23187, BSA-zuc binding was lost in the apical segment of the acrosome but remained in the equatorial segment and postacrosome regions. BSA-Gal binding to the equatorial region was increased. In the presence of 2.5 μg ml(-1) BSA-Fuc, in vitro sperm-ZP binding was significantly decreased, indicating that fucosyl BSA functionally mimics ZP glycoproteins during sperm-egg ZP interactions. At the same concentration, BSA-Gal was not effective. Fucosyl BSA that efficiently inhibited the sperm-ZP binding can mimic the ZP glycoconjugate and has potential for use as a sperm fertility control agent in mouse. © 2012 Blackwell Verlag GmbH.

  18. CLIPZ: a database and analysis environment for experimentally determined binding sites of RNA-binding proteins.

    Science.gov (United States)

    Khorshid, Mohsen; Rodak, Christoph; Zavolan, Mihaela

    2011-01-01

    The stability, localization and translation rate of mRNAs are regulated by a multitude of RNA-binding proteins (RBPs) that find their targets directly or with the help of guide RNAs. Among the experimental methods for mapping RBP binding sites, cross-linking and immunoprecipitation (CLIP) coupled with deep sequencing provides transcriptome-wide coverage as well as high resolution. However, partly due to their vast volume, the data that were so far generated in CLIP experiments have not been put in a form that enables fast and interactive exploration of binding sites. To address this need, we have developed the CLIPZ database and analysis environment. Binding site data for RBPs such as Argonaute 1-4, Insulin-like growth factor II mRNA-binding protein 1-3, TNRC6 proteins A-C, Pumilio 2, Quaking and Polypyrimidine tract binding protein can be visualized at the level of the genome and of individual transcripts. Individual users can upload their own sequence data sets while being able to limit the access to these data to specific users, and analyses of the public and private data sets can be performed interactively. CLIPZ, available at http://www.clipz.unibas.ch, aims to provide an open access repository of information for post-transcriptional regulatory elements.

  19. Causal binding of actions to their effects.

    Science.gov (United States)

    Buehner, Marc J; Humphreys, Gruffydd R

    2009-10-01

    According to widely held views in cognitive science harking back to David Hume, causality cannot be perceived directly, but instead is inferred from patterns of sensory experience, and the quality of these inferences is determined by perceivable quantities such as contingency and contiguity. We report results that suggest a reversal of Hume's conjecture: People's sense of time is warped by the experience of causality. In a stimulus-anticipation task, participants' response behavior reflected a shortened experience of time in the case of target stimuli participants themselves had generated, relative to equidistant, equally predictable stimuli they had not caused. These findings suggest that causality in the mind leads to temporal binding of cause and effect, and extend and generalize beyond earlier claims of intentional binding between action and outcome.

  20. Tight-binding treatment of conjugated polymers

    DEFF Research Database (Denmark)

    Lynge, Thomas Bastholm

    This PhD thesis concerns conjugated polymers which constitute a constantly growing research area. Today, among other things, conjugated polymers play a role in plastic based solar cells, photodetectors and light emitting diodes, and even today such plastic-based components constitute an alternative...... of tomorrow. This thesis specifically treats the three conjugated polymers trans-polyacetylene (tPA), poly(para-phenylene) (PPP) and poly(para-phe\\-nylene vinylene) (PPV). The present results, which are derived within the tight-binding model, are divided into two parts. In one part, analytic results...... are derived for the optical properties of the polymers expressed in terms of the optical susceptibility both in the presence and in the absence of a static electric field. In the other part, the cumputationally efficient Density Functional-based Tight-Binding (DFTB) model is applied to the description...

  1. Comparison of Transcription Factor Binding Site Models

    KAUST Repository

    Bhuyan, Sharifulislam

    2012-05-01

    Modeling of transcription factor binding sites (TFBSs) and TFBS prediction on genomic sequences are important steps to elucidate transcription regulatory mechanism. Dependency of transcription regulation on a great number of factors such as chemical specificity, molecular structure, genomic and epigenetic characteristics, long distance interaction, makes this a challenging problem. Different experimental procedures generate evidence that DNA-binding domains of transcription factors show considerable DNA sequence specificity. Probabilistic modeling of TFBSs has been moderately successful in identifying patterns from a family of sequences. In this study, we compare performances of different probabilistic models and try to estimate their efficacy over experimental TFBSs data. We build a pipeline to calculate sensitivity and specificity from aligned TFBS sequences for several probabilistic models, such as Markov chains, hidden Markov models, Bayesian networks. Our work, containing relevant statistics and evaluation for the models, can help researchers to choose the most appropriate model for the problem at hand.

  2. Binding of 3H-iloprost to rat gastric mucosa: a pitfall in performing radioligand binding assays

    International Nuclear Information System (INIS)

    Beinborn, M.; Kromer, W.; Staar, U.; Sewing, K.F.

    1985-01-01

    Binding of 3 H-iloprost was studied in a 20,000 x g sediment of the rat gastric mucosa. When pH in both test tubes for total and non-specific binding was kept identical, no displaceable binding of iloprost could be detected. When no care was taken to keep the pH identical in corresponding test tubes of the binding assay, changes in pH simulated specific and displaceable binding of iloprost. Therefore it is concluded that - in contrast to earlier reports - it is not possible to demonstrate specific iloprost binding using the given method

  3. Antimicrobial Peptides with Differential Bacterial Binding Characteristics

    Science.gov (United States)

    2013-03-01

    wherein each residue in the sequence is systematically replaced with alanine to produce a set of well-defined mutations, and 3) sequence generation...peptide sequences with differential binding behavior toward select microorganisms .  viii    Acknowledgements The authors would like to thank Mr. Steven...A., Sandri, L., & Giangaspero, A. (2000). Amphipathic, α-Helical Antimicrobial Peptides. Biopolymers , 55, 4-30.  2 Epand, R. M., & Vogel, H. J. (1999

  4. Iodide Binding in Sodium-Coupled Cotransporters.

    Science.gov (United States)

    Vergara-Jaque, Ariela; Fong, Peying; Comer, Jeffrey

    2017-12-26

    Several apical iodide translocation pathways have been proposed for iodide efflux out of thyroid follicular cells, including a pathway mediated by the sodium-coupled monocarboxylate transporter 1 (SMCT1), which remains controversial. Herein, we evaluate structural and functional similarities between SMCT1 and the well-studied sodium-iodide symporter (NIS) that mediates the first step of iodide entry into the thyroid. Free-energy calculations using a force field with electronic polarizability verify the presence of a conserved iodide-binding pocket between the TM2, TM3, and TM7 segments in hNIS, where iodide is coordinated by Phe67, Gln72, Cys91, and Gln94. We demonstrate the mutation of residue Gly93 of hNIS to a larger amino acid expels the side chain of a critical tryptophan residue (Trp255) into the interior of the binding pocket, partially occluding the iodide binding site and reducing iodide affinity, which is consistent with previous reports associating mutation of this residue with iodide uptake deficiency and hypothyroidism. Furthermore, we find that the position of Trp255 in this hNIS mutant mirrors that of Trp253 in wild-type hSMCT1, where a threonine (Thr91) occupies the position homologous to that occupied by glycine in wild-type hNIS (Gly93). Correspondingly, mutation of Thr91 to glycine in hSMCT1 makes the pocket structure more like that of wild-type hNIS, increasing its iodide affinity. These results suggest that wild-type hSMCT1 in the inward-facing conformation may bind iodide only very weakly, which may have implications for its ability to transport iodide.

  5. Asymmetric Aminalization via Cation-Binding Catalysis

    DEFF Research Database (Denmark)

    Park, Sang Yeon; Liu, Yidong; Oh, Joong Suk

    2018-01-01

    Asymmetric cation-binding catalysis, in principle, can generate "chiral" anionic nucleophiles, where the counter cations are coordinated within chiral environments. Nitrogen-nucleophiles are intrinsically basic, therefore, its use as nucleophiles is often challenging and limiting the scope...... of the reaction. Particularly, a formation of configurationally labile aminal centers with alkyl substituents has been a formidable challenge due to the enamine/imine equilibrium of electrophilic substrates. Herein, we report enantioselective nucleophilic addition reactions of potassium phthalimides to Boc-protected...

  6. Polypeptide binding properties of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, C S; Heegaard, N H; Holm, A

    2000-01-01

    to be elucidated. We have investigated the interactions of human calreticulin with denatured ovalbumin, proteolytic digests of ovalbumin, and different available peptides by solid phase assays, size-exclusion chromatography, capillary electrophoresis, and MS. The results show that calreticulin interacts better...... with unfolded ovalbumin than with native ovalbumin, that calreticulin strongly binds components in proteolytic digests of denatured ovalbumin, and that calreticulin interacts strongly with certain synthetic peptides....

  7. What Happened to the IGF Binding Proteins?

    Science.gov (United States)

    Bach, Leon A

    2018-02-01

    Insulinlike growth factor (IGF) binding proteins (IGFBPs) 1 to 6 are high-affinity regulators of IGF activity. They generally inhibit IGF actions by preventing binding to the IGF-I receptor but can also enhance their actions under some conditions. Posttranslational modifications such as glycosylation and phosphorylation modulate IGFBP properties, and IGFBP proteolysis results in IGF release. IGFBPs have more recently been shown to have IGF-independent actions. A number of mechanisms are involved, including modulation of other growth factor pathways, nuclear localization and transcriptional regulation, interaction with the sphingolipid pathway, and binding to non-IGF biomolecules in the extracellular space and matrix, on the cell surface and intracellularly. IGFBPs modulate important biological processes, including cell proliferation, survival, migration, senescence, autophagy, and angiogenesis. Their actions have been implicated in growth, metabolism, cancer, stem cell maintenance and differentiation, and immune regulation. Recent studies have shown that epigenetic mechanisms are involved in the regulation of IGFBP abundance. A more complete understanding of IGFBP biology is necessary to further define their cellular roles and determine their therapeutic potential. Copyright © 2018 Endocrine Society.

  8. Binding Energy and Equilibrium of Compact Objects

    Directory of Open Access Journals (Sweden)

    Germano M.

    2014-04-01

    Full Text Available The theoretical analysis of the existence of a limit mass for compact astronomic ob- jects requires the solution of the Einstein’s equations of g eneral relativity together with an appropriate equation of state. Analytical solutions exi st in some special cases like the spherically symmetric static object without energy sou rces that is here considered. Solutions, i.e. the spacetime metrics, can have a singular m athematical form (the so called Schwarzschild metric due to Hilbert or a nonsingula r form (original work of Schwarzschild. The former predicts a limit mass and, conse quently, the existence of black holes above this limit. Here it is shown that, the origi nal Schwarzschild met- ric permits compact objects, without mass limit, having rea sonable values for central density and pressure. The lack of a limit mass is also demonst rated analytically just imposing reasonable conditions on the energy-matter densi ty, of positivity and decreas- ing with radius. Finally the ratio between proper mass and to tal mass tends to 2 for high values of mass so that the binding energy reaches the lim it m (total mass seen by a distant observer. As it is known the negative binding energ y reduces the gravitational mass of the object; the limit of m for the binding energy provides a mechanism for stable equilibrium of any amount of mass to contrast the gravitatio nal collapse.

  9. The aesthetic experience of 'contour binding'.

    Science.gov (United States)

    Casco, Clara; Guzzon, Daniela

    2008-01-01

    To find the diagnostic spatial frequency information in different painting styles (cubism, impressionism and realism), we have compared sensitivity (d') in distinguishing signal (subject of the painting) from noise with normal, high-pass and low-pass filtered images at long (150 ms) and short (30 ms) exposure. We found that for cubist-style images, d' increases with high-pass filtering compared with normal and low-pass filtered images, but decreases with low-pass filtering compared with normal images. These results indicate that channels with high spatial resolution provide the diagnostic information to solve the binding problem. Sensitivity for images in impressionist style was instead reduced by both low- and high-pass filtering. This indicates that both high and low spatial frequency channels play a role in solving the binding problem, suggesting the involvement of large collator units that group the response of small channels tuned to the same orientation. The difference between realism, which shows higher sensitivity for low-frequency filtering at short durations and cubism in which the binding problem is solved by high spatial frequency channels, has a corresponding difference in aesthetic judgment: the probability of judging a painting as 'intriguing' is larger with low-pass filtering than with high-pass filtering in realism, while the opposite is true for cubism. This suggests that the aesthetic experience is available during early processing of an image, and could preferentially influence high-level categorization of the subject of a painting.

  10. Computation of pH-Dependent Binding Free Energies

    Science.gov (United States)

    Kim, M. Olivia; McCammon, J. Andrew

    2015-01-01

    Protein-ligand binding accompanies changes in the surrounding electrostatic environments of the two binding partners and may lead to changes in protonation upon binding. In cases where the complex formation results in a net transfer of protons, the binding process is pH-dependent. However, conventional free energy computations or molecular docking protocols typically employ fixed protonation states for the titratable groups in both binding partners set a priori, which are identical for the free and bound states. In this review, we draw attention to these important yet largely ignored binding-induced protonation changes in protein-ligand association by outlining physical origins and prevalence of the protonation changes upon binding. Following a summary of various theoretical methods for pKa prediction, we discuss the theoretical framework to examine the pH dependence of protein-ligand binding processes. PMID:26202905

  11. Genetics Home Reference: core binding factor acute myeloid leukemia

    Science.gov (United States)

    ... acute myeloid leukemia Core binding factor acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... collapse boxes. Description Core binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer ...

  12. Association of HLA Types with Non-Specific Binding of Negative Control Beads in Luminex Panel Reactive Antibody (PRA) Screening Assay.

    Science.gov (United States)

    Lee, Nuri; Park, Hee Sue; In, Ji Won; Roh, Eun Youn; Shin, Sue; Park, Kyoung Un; Song, Eun Young

    2017-01-01

    Luminex panel reactive antibody (PRA) screening assays using microbeads are widely used for organ transplantation. Anti-HLA serum reactivity is calculated by correcting for non-specific binding to the negative control (NC) beads. High mean fluorescence intensity (MFI) value of NC beads are observed in some patients and can result in false negative results in the PRA screening assay. We analyzed the clinical characteristics and HLA types of those patients with high MFI values of NC beads. Sixty-six patients with high MFI values of NC beads (> 300) in the PRA LABScreen Mixed assay (One Lambda) tested were included as the high NC group. Age and gender matched controls with low MFI values of NC beads (PRA, were selected as the low NC group and 207 healthy Koreans were used as normal controls. Association of clinical characteristics and HLA types with the high NC group were analyzed using Chi-square test or Fischer's exact test, as appropriate. The proportion of patients with underlying liver disease was higher in the high NC group compared to the low NC group (18.1% vs. 1.5%, p < 0.001, OR = 14.2). The seropositivity of anti-nuclear antibody and rheumatoid factor, the frequency of use of intravenous immunoglobulin G, anti-thymocyte globulin, and rituximab showed no difference between two groups. The phenotype frequency (PF) of HLA-B46 was higher in the high NC group than in the low NC group (8.0% vs. 3.2%, p = 0.036, OR = 2.8). The PF of HLA-B7 was lower in the high NC group than in the healthy controls (0.0% vs. 6.5%, p = 0.008, OR = 0.1). The PF of HLA-DR1 was lower in the high NC group than in the low NC group (0.8% vs. 6.6%, p = 0.015, OR = 0.1) or healthy controls (0.8% vs. 7.4%, p = 0.003, Pc = 0.042, OR = 0.1). Increased non-specific binding to NC beads was associated with underlying liver disease and HLAB46. HLA-B7 and HLA-DR1 were related to a lower chance of non-specific binding to NC beads. The mechanism of those associations, such as differences in non

  13. Binding Studies of Lamotrigine with Sera of Different Animal Species

    African Journals Online (AJOL)

    Erah

    into the mechanism of interaction, evaluate the effect of dielectric constant on binding affinity, and to determine the effect of ..... Physico-chemical aspects of protein binding of nimesulide, Ind J. Pharm Sci, 2005; 2: 243-246. 10. Dutta, SK, Basu, SK, Sen KK. Binding of diclofenac sodium with bovine serum albumin at different ...

  14. Atomistic fingerprint of hyaluronan-CD44 binding

    DEFF Research Database (Denmark)

    Vuorio, Joni; Vattulainen, Ilpo; Martinez-Seara, Hector

    2017-01-01

    that hyaluronan can bind CD44 with three topographically different binding modes that in unison define an interaction fingerprint, thus providing a plausible explanation for the disagreement between the earlier studies. Our results confirm that the known crystallographic mode is the strongest of the three binding...

  15. Binding of Intrinsic and Extrinsic Features in Working Memory

    Science.gov (United States)

    Ecker, Ullrich K. H.; Maybery, Murray; Zimmer, Hubert D.

    2013-01-01

    There is ongoing debate concerning the mechanisms of feature binding in working memory. In particular, there is controversy regarding the extent to which these binding processes are automatic. The present article demonstrates that binding mechanisms differ depending on whether the to-be-integrated features are perceived as forming a coherent…

  16. Thioredoxin binding site of phosphoribulokinase overlaps the catalytic site

    International Nuclear Information System (INIS)

    Porter, M.A.; Hartman, F.C.

    1986-01-01

    The ATP-regulatory binding site of phosphoribulokinase was studied using bromoacetylethanolamine phosphate (BrAcNHEtOP). BrAcNHEtOP binds to the active-regulatory binding site of the protein. Following trypsin degradation of the labeled protein, fragments were separated by HPLC and sequenced. (DT)

  17. A sequential binding mechanism in a PDZ domain

    DEFF Research Database (Denmark)

    Chi, Celestine N; Bach, Anders; Engström, Åke

    2009-01-01

    that ligand binding involves at least a two-step process. By using an ultrarapid continuous-flow mixer, we then detected a hyperbolic dependence of binding rate constants on peptide concentration, corroborating the two-step binding mechanism. Furthermore, we found a similar dependence of the rate constants...

  18. A structural classification of substrate-binding proteins

    NARCIS (Netherlands)

    Berntsson, Ronnie P. -A.; Smits, Sander H. J.; Schmitt, Lutz; Slotboom, Dirk-Jan; Poolman, Bert

    2010-01-01

    Substrate-binding proteins (SBP) are associated with a wide variety of protein complexes. The proteins are part of ATP-binding cassette transporters for substrate uptake, ion gradient driven transporters, DNA-binding proteins, as well as channels and receptors from both pro-and eukaryotes. A wealth

  19. NMR studies on DNA binding specificity of the lac repressor

    NARCIS (Netherlands)

    Kopke Salinas, Roberto

    2005-01-01

    The thesis describes NMR structures of two protein-DNA complexes. The first structure shows how the protein, the DNA binding domain of lac repressor, recognizes its natural DNA binding site, by adaptation and read out of the nucleotide sequence. The second one shows how the DNA binding specificity

  20. Peptide Nucleic Acids Having Enhanced Binding Affinity and Sequence Specificity

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. Methods of increasing binding affinity and sequence specificity of peptide nucleic acids...

  1. Tritium NMR spectroscopy of ligand binding to maltose-binding protein

    Energy Technology Data Exchange (ETDEWEB)

    Gehring, K.; Williams, P.G.; Pelton, J.G.; Morimoto, H.; Wemmer, D.E. (Lawrence Berkeley Lab., CA (United States))

    1991-06-04

    Tritium-labeled {alpha}- and {beta}-maltodextrins have been used to study their complexes with maltose-binding protein (MBP), a 40-kDa bacterial protein. Five substrates, from maltose to maltohexaose, were labeled at their reducing ends and their binding studied. Tritium NMR specctroscopy of the labeled sugars showed large upfield chamical shift changes upon binding and strong anomeric specficity. At 10{degrees}C, MBP bound {alpha}-maltose with 2.7 {plus minus} 0.5-fold higher affinity than {beta}-maltose, and, for longer maltodextrins, the ratio of affinities was even larger. The maximum chemical shift change was 2.2 ppm, suggesting that the reducing end of bound {alpha}-maltodextrin makes close contact with an aromatic residue in the MBP-binding site. Experiments with maltotriose (and longer maltodextrins) also revealed the presence of two bound {beta}-maltotriose resonances in rapid exchange. The authors interpret these two resonances as arising from two distinct sugar-protein complexes. In one complex, the {beta}-maltodextrin is bound by its reducing end, and, in the other complex, the {beta}-maltodextrin is bound by the middle glucose residue(s). This interpretation also suggests how MBP is able to bind both linear and circular maltodextrins.

  2. The Receptor Binding Domain of Botulinum Neurotoxin Stereotype C Binds Phosphoinositides

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yanfeng; Varnum, Susan M.

    2012-03-01

    Botulinum neurotoxins (BoNTs) are the most toxic proteins known for humans and animals with an extremely low LD50 of {approx} 1 ng/kg. BoNTs generally require a protein and a ganglioside on the cell membrane surface for binding, which is known as a 'dual receptor' mechanism for host intoxication. Recent studies have suggested that in addition to gangliosides, other membrane lipids such as phosphoinositides may be involved in the interactions with the receptor binding domain (HCR) of BoNTs for better membrane penetration. Here, using two independent lipid-binding assays, we tested the interactions of BoNT/C-HCR with lipids in vitro. BoNT/C-HCR was found to bind negatively charged phospholipids, preferentially phosphoinositides. Additional interactions to phosphoinositides may help BoNT/C bind membrane more tightly and transduct signals for subsequent steps of intoxication. Our results provide new insights into the mechanisms of host cell membrane recognition by BoNTs.

  3. Ail binding to fibronectin facilitates Yersinia pestis binding to host cells and Yop delivery.

    Science.gov (United States)

    Tsang, Tiffany M; Felek, Suleyman; Krukonis, Eric S

    2010-08-01

    Yersinia pestis, the causative agent of plague, evades host immune responses and rapidly causes disease. The Y. pestis adhesin Ail mediates host cell binding and is critical for Yop delivery. To identify the Ail receptor(s), Ail was purified following overexpression in Escherichia coli. Ail bound specifically to fibronectin, an extracellular matrix protein with the potential to act as a bridge between Ail and host cells. Ail expressed by E. coli also mediated binding to purified fibronectin, and Ail-mediated E. coli adhesion to host cells was dependent on fibronectin. Ail expressed by Y. pestis bound purified fibronectin, as did the Y. pestis adhesin plasminogen activator (Pla). However, a KIM5 Delta ail mutant had decreased binding to host cells, while a KIM5 Delta pla mutant had no significant defect in adhesion. Furthermore, treatment with antifibronectin antibodies decreased Ail-mediated adhesion by KIM5 and the KIM5 Delta pla mutant, indicating that the Ail-fibronectin interaction was important for cell binding. Finally, antifibronectin antibodies inhibited the KIM5-mediated cytotoxicity of host cells in an Ail-dependent fashion. These data indicate that Ail is a key adhesin that mediates binding to host cells through interaction with fibronectin on the surface of host cells, and this interaction is important for Yop delivery by Y. pestis.

  4. Ail Binding to Fibronectin Facilitates Yersinia pestis Binding to Host Cells and Yop Delivery▿

    Science.gov (United States)

    Tsang, Tiffany M.; Felek, Suleyman; Krukonis, Eric S.

    2010-01-01

    Yersinia pestis, the causative agent of plague, evades host immune responses and rapidly causes disease. The Y. pestis adhesin Ail mediates host cell binding and is critical for Yop delivery. To identify the Ail receptor(s), Ail was purified following overexpression in Escherichia coli. Ail bound specifically to fibronectin, an extracellular matrix protein with the potential to act as a bridge between Ail and host cells. Ail expressed by E. coli also mediated binding to purified fibronectin, and Ail-mediated E. coli adhesion to host cells was dependent on fibronectin. Ail expressed by Y. pestis bound purified fibronectin, as did the Y. pestis adhesin plasminogen activator (Pla). However, a KIM5 Δail mutant had decreased binding to host cells, while a KIM5 Δpla mutant had no significant defect in adhesion. Furthermore, treatment with antifibronectin antibodies decreased Ail-mediated adhesion by KIM5 and the KIM5 Δpla mutant, indicating that the Ail-fibronectin interaction was important for cell binding. Finally, antifibronectin antibodies inhibited the KIM5-mediated cytotoxicity of host cells in an Ail-dependent fashion. These data indicate that Ail is a key adhesin that mediates binding to host cells through interaction with fibronectin on the surface of host cells, and this interaction is important for Yop delivery by Y. pestis. PMID:20498264

  5. Tritium NMR spectroscopy of ligand binding to maltose-binding protein

    International Nuclear Information System (INIS)

    Gehring, K.; Williams, P.G.; Pelton, J.G.; Morimoto, H.; Wemmer, D.E.

    1991-01-01

    Tritium-labeled α- and β-maltodextrins have been used to study their complexes with maltose-binding protein (MBP), a 40-kDa bacterial protein. Five substrates, from maltose to maltohexaose, were labeled at their reducing ends and their binding studied. Tritium NMR specctroscopy of the labeled sugars showed large upfield chamical shift changes upon binding and strong anomeric specficity. At 10 degrees C, MBP bound α-maltose with 2.7 ± 0.5-fold higher affinity than β-maltose, and, for longer maltodextrins, the ratio of affinities was even larger. The maximum chemical shift change was 2.2 ppm, suggesting that the reducing end of bound α-maltodextrin makes close contact with an aromatic residue in the MBP-binding site. Experiments with maltotriose (and longer maltodextrins) also revealed the presence of two bound β-maltotriose resonances in rapid exchange. The authors interpret these two resonances as arising from two distinct sugar-protein complexes. In one complex, the β-maltodextrin is bound by its reducing end, and, in the other complex, the β-maltodextrin is bound by the middle glucose residue(s). This interpretation also suggests how MBP is able to bind both linear and circular maltodextrins

  6. Zooming into the binding groove of HLA molecules : which positions and which substitutions change peptide binding most?

    NARCIS (Netherlands)

    van Deutekom, Hanneke W M; Kesmir, C.

    Human leukocyte antigen (HLA) genes are the most polymorphic genes in the human genome. Almost all polymorphic residues are located in the peptide-binding groove, resulting in different peptide-binding preferences. Whether a single amino acid change can alter the peptide-binding repertoire of an HLA

  7. Cooperative binding of copper(I) to the metal binding domains in Menkes disease protein

    DEFF Research Database (Denmark)

    Jensen, P Y; Bonander, N; Møller, L B

    1999-01-01

    spectroscopy, and their copper(I) binding properties have been determined. Structure prediction derived from far-UV CD indicates that the secondary structure is similar in the three proteins and dominated by beta-sheet. The tryptophan fluorescence maximum is blue-shifted in the constructs containing two...... and six MBDs relative to the monomer, suggesting more structurally buried tryptophan(s), compared to the single MBD construct. Copper(I) binding has been studied by equilibrium dialysis under anaerobic conditions. We show that the copper(I) binding to constructs containing two and six domains...... is cooperative, with Hill coefficients of 1.5 and 4, respectively. The apparent affinities are described by K(0.5), determined to be 65 microM and 19 microM for constructs containing two and six domains, respectively. Our data reveal a unique regulation of Menkes protein upon a change in copper(I) concentration...

  8. Acyl-CoA-binding protein/diazepam-binding inhibitor gene and pseudogenes

    DEFF Research Database (Denmark)

    Mandrup, S; Hummel, R; Ravn, S

    1992-01-01

    modulator of the GABAA receptor in brain membranes. ACBP/DBI, or proteolytically derived polypeptides of ACBP/DBI, have also been implicated in the control of steroidogenesis in mitochondria and glucose-stimulated insulin secretion. Thus, it appears that ACBP/DBI is a remarkable, versatile protein. Now we......Acyl-CoA-binding protein (ACBP) is a 10 kDa protein isolated from bovine liver by virtue of its ability to bind and induce the synthesis of medium-chain acyl-CoA esters. Surprisingly, it turned out to be identical to a protein named diazepam-binding Inhibitor (DBI) claimed to be an endogenous....... There is a remarkable correspondence between the structural modules of ACBP/DBI as determined by 1H nuclear magnetic resonance spectroscopy and the exon-intron architecture of the ACBP/DBI gene. Detailed analyses of transcription of the ACBP/DBI gene in brain and liver were performed to map transcription initiation...

  9. Autoradiographic localization of benzomorphan binding sites in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Crain, B.J.; Kwenjen Chang; McNamara, J.O.; Valdes, F.

    1985-07-17

    The benzomorphan subpopulation of opiate binding sites was labeled by (TH)diprenorphine in the presence of unlabeled ligands selected to quench and delta opiate binding sites. The distribution of benzomorphan binding sites was then localized autoradiographically. The distribution differs from the distributions of , delta and kappa opiate binding and is quite similar to the distribution of US -endorphin immunoreactivity. These observations support the hypothesis, based on biochemical studies in brain membranes, that benzomorphan binding sites may represent the ligand recognition sites of putative epsilon receptors. (Auth.). 34 refs.; 3 figs.

  10. Dual chain synthetic heparin-binding growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY

    2009-10-06

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  11. Helical propensity in an intrinsically disordered protein accelerates ligand binding

    DEFF Research Database (Denmark)

    Iesmantavicius, Vytautas; Dogan, Jakob; Jemth, Per

    2014-01-01

    domain of the activator for thyroid hormone and retinoid receptors (ACTR) is intrinsically disordered and folds upon binding to the nuclear coactivator binding domain (NCBD) of the CREB binding protein. A number of mutants was designed that selectively perturbs the amount of secondary structure......Many intrinsically disordered proteins fold upon binding to other macromolecules. The secondary structure present in the well-ordered complex is often formed transiently in the unbound state. The consequence of such transient structure for the binding process is, however, not clear. The activation...... the notion of preformed secondary structure as an important determinant for molecular recognition in intrinsically disordered proteins....

  12. Structural basis for PECAM-1 homophilic binding

    Energy Technology Data Exchange (ETDEWEB)

    Paddock, Cathy; Zhou, Dongwen; Lertkiatmongkol, Panida; Newman, Peter J.; Zhu, Jieqing (MCW)

    2015-12-23

    Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a 130-kDa member of the immunoglobulin gene superfamily (IgSF) that is present on the surface of circulating platelets and leukocytes, and highly expressed at the junctions of confluent endothelial cell monolayers. PECAM-1–mediated homophilic interactions, known to be mediated by its 2 amino-terminal immunoglobulin homology domains, are essential for concentrating PECAM-1 at endothelial cell intercellular junctions, where it functions to facilitate diapedesis, maintain vascular integrity, and transmit survival signals into the cell. Given the importance of PECAM-1–mediated homophilic interactions in mediating each of these cell physiological events, and to reveal the nature and orientation of the PECAM-1–PECAM-1 homophilic-binding interface, we undertook studies aimed at determining the crystal structure of the PECAM-1 homophilic-binding domain, which is composed of amino-terminal immunoglobulin homology domains 1 and 2 (IgD1 and IgD2). The crystal structure revealed that both IgD1 and IgD2 exhibit a classical IgSF fold, having a β-sandwich topology formed by 2 sheets of antiparallel β strands stabilized by the hallmark disulfide bond between the B and F strands. Interestingly, despite previous assignment to the C2 class of immunoglobulin-like domains, the structure of IgD1 reveals that it actually belongs to the I2 set of IgSF folds. Both IgD1 and IgD2 participate importantly in the formation of the trans homophilic-binding interface, with a total buried interface area of >2300 Å2. These and other unique structural features of PECAM-1 allow for the development of an atomic-level model of the interactions that PECAM-1 forms during assembly of endothelial cell intercellular junctions.

  13. Antioxidant flavonoids bind human serum albumin

    Science.gov (United States)

    Kanakis, C. D.; Tarantilis, P. A.; Polissiou, M. G.; Diamantoglou, S.; Tajmir-Riahi, H. A.

    2006-10-01

    Human serum albumin (HSA) is a principal extracellular protein with a high concentration in blood plasma and carrier for many drugs to different molecular targets. Flavonoids are powerful antioxidants and prevent DNA damage. The antioxidative protections are related to their binding modes to DNA duplex and complexation with free radicals in vivo. However, flavonoids are known to inhibit the activities of several enzymes such as calcium phospholipid-dependent protein kinase, tyrosine protein kinase from rat lung, phosphorylase kinase, phosphatidylinositol 3-kinase and DNA topoisomerases that exhibit the importance of flavonoid-protein interaction. This study was designed to examine the interaction of human serum albumin (HSA) with quercetin (que), kaempferol (kae) and delphinidin (del) in aqueous solution at physiological conditions, using constant protein concentration of 0.25 mM (final) and various drug contents of 1 μM-1 mM. FTIR and UV-vis spectroscopic methods were used to determine the polyphenolic binding mode, the binding constant and the effects of flavonoid complexation on protein secondary structure. The spectroscopic results showed that flavonoids are located along the polypeptide chains through H-bonding interactions with overall affinity constant of Kque = 1.4 × 10 4 M -1, Kkae = 2.6 × 10 5 M -1 and Kdel = 4.71 × 10 5 M -1. The protein secondary structure showed no alterations at low pigment concentration (1 μM), whereas at high flavonoid content (1 mM), major reduction of α-helix from 55% (free HSA) to 42-46% and increase of β-sheet from 15% (free HSA) to 17-19% and β-anti from 7% (free HSA) to 10-20% occurred in the flavonoid-HSA adducts. The major reduction of HSA α-helix is indicative of a partial protein unfolding upon flavonoid interaction.

  14. End binding proteins are obligatory dimers.

    Directory of Open Access Journals (Sweden)

    Indrani Sen

    Full Text Available End binding (EB proteins are responsible for the recruitment of an array of microtubule plus-end tracking proteins (+TIPs to growing microtubules ends. EBs encompass an N-terminal calponin homology domain that confers microtubule tip tracking activity to the protein. The C-terminal domain of EBs contains a coiled coil that mediates the parallel dimerization of EB monomers. This part of the protein is also responsible for partner binding. While dimerization is not essential for microtubule tip tracking by EBs it is a prerequisite for +TIP partner binding. The concentration of EBs in cells has been estimated to be in the range of hundreds of nanomoles. In contrast, in in vitro single molecule experiments EB concentrations of subnanomoles are employed. From a mechanistic point of view it is important to assess the oligomerization state of EBs at physiologically and experimentally relevant protein concentrations, in particular if the goal of a study is to model the behavior of EB-dependent dynamic +TIP networks. Here we have determined the stability of the EB1 and EB3 dimers using multi-angle light scattering and fluorescence analytical ultracentrifugation. We show that these EBs form stable dimers and do not dissociate even at very low nanomolar concentrations. The dimers remained stable at both room temperature as well as at the physiologically relevant temperature of 37°C. Together, our results reveal that EBs are obligatory dimers, a conclusion that has implications for the mechanistic understanding of these key proteins involved in the orchestration of dynamic protein networks at growing microtubule ends.

  15. DNA and RNA Quadruplex-Binding Proteins

    Directory of Open Access Journals (Sweden)

    Václav Brázda

    2014-09-01

    Full Text Available Four-stranded DNA structures were structurally characterized in vitro by NMR, X-ray and Circular Dichroism spectroscopy in detail. Among the different types of quadruplexes (i-Motifs, minor groove quadruplexes, G-quadruplexes, etc., the best described are G-quadruplexes which are featured by Hoogsteen base-paring. Sequences with the potential to form quadruplexes are widely present in genome of all organisms. They are found often in repetitive sequences such as telomeric ones, and also in promoter regions and 5' non-coding sequences. Recently, many proteins with binding affinity to G-quadruplexes have been identified. One of the initially portrayed G-rich regions, the human telomeric sequence (TTAGGGn, is recognized by many proteins which can modulate telomerase activity. Sequences with the potential to form G-quadruplexes are often located in promoter regions of various oncogenes. The NHE III1 region of the c-MYC promoter has been shown to interact with nucleolin protein as well as other G-quadruplex-binding proteins. A number of G-rich sequences are also present in promoter region of estrogen receptor alpha. In addition to DNA quadruplexes, RNA quadruplexes, which are critical in translational regulation, have also been predicted and observed. For example, the RNA quadruplex formation in telomere-repeat-containing RNA is involved in interaction with TRF2 (telomere repeat binding factor 2 and plays key role in telomere regulation. All these fundamental examples suggest the importance of quadruplex structures in cell processes and their understanding may provide better insight into aging and disease development.

  16. Human pentraxin 3 binds to the complement regulator c4b-binding protein.

    Directory of Open Access Journals (Sweden)

    Anne Braunschweig

    Full Text Available The long pentraxin 3 (PTX3 is a soluble recognition molecule with multiple functions including innate immune defense against certain microbes and the clearance of apoptotic cells. PTX3 interacts with recognition molecules of the classical and lectin complement pathways and thus initiates complement activation. In addition, binding of PTX3 to the alternative complement pathway regulator factor H was shown. Here, we show that PTX3 binds to the classical and lectin pathway regulator C4b-binding protein (C4BP. A PTX3-binding site was identified within short consensus repeats 1-3 of the C4BP α-chain. PTX3 did not interfere with the cofactor activity of C4BP in the fluid phase and C4BP maintained its complement regulatory activity when bound to PTX3 on surfaces. While C4BP and factor H did not compete for PTX3 binding, the interaction of C4BP with PTX3 was inhibited by C1q and by L-ficolin. PTX3 bound to human fibroblast- and endothelial cell-derived extracellular matrices and recruited functionally active C4BP to these surfaces. Whereas PTX3 enhanced the activation of the classical/lectin pathway and caused enhanced C3 deposition on extracellular matrix, deposition of terminal pathway components and the generation of the inflammatory mediator C5a were not increased. Furthermore, PTX3 enhanced the binding of C4BP to late apoptotic cells, which resulted in an increased rate of inactivation of cell surface bound C4b and a reduction in the deposition of C5b-9. Thus, in addition to complement activators, PTX3 interacts with complement inhibitors including C4BP. This balanced interaction on extracellular matrix and on apoptotic cells may prevent excessive local complement activation that would otherwise lead to inflammation and host tissue damage.

  17. Glycan masking of Plasmodium vivax Duffy Binding Protein for probing protein binding function and vaccine development.

    Directory of Open Access Journals (Sweden)

    Sowmya Sampath

    Full Text Available Glycan masking is an emerging vaccine design strategy to focus antibody responses to specific epitopes, but it has mostly been evaluated on the already heavily glycosylated HIV gp120 envelope glycoprotein. Here this approach was used to investigate the binding interaction of Plasmodium vivax Duffy Binding Protein (PvDBP and the Duffy Antigen Receptor for Chemokines (DARC and to evaluate if glycan-masked PvDBPII immunogens would focus the antibody response on key interaction surfaces. Four variants of PVDBPII were generated and probed for function and immunogenicity. Whereas two PvDBPII glycosylation variants with increased glycan surface coverage distant from predicted interaction sites had equivalent binding activity to wild-type protein, one of them elicited slightly better DARC-binding-inhibitory activity than wild-type immunogen. Conversely, the addition of an N-glycosylation site adjacent to a predicted PvDBP interaction site both abolished its interaction with DARC and resulted in weaker inhibitory antibody responses. PvDBP is composed of three subdomains and is thought to function as a dimer; a meta-analysis of published PvDBP mutants and the new DBPII glycosylation variants indicates that critical DARC binding residues are concentrated at the dimer interface and along a relatively flat surface spanning portions of two subdomains. Our findings suggest that DARC-binding-inhibitory antibody epitope(s lie close to the predicted DARC interaction site, and that addition of N-glycan sites distant from this site may augment inhibitory antibodies. Thus, glycan resurfacing is an attractive and feasible tool to investigate protein structure-function, and glycan-masked PvDBPII immunogens might contribute to P. vivax vaccine development.

  18. Synthesis, estrogen receptor binding, and tissue distribution of a new iodovinylestradiol derivative (17α,20E)-21-[123I]iodo-11β-nitrato-19-norpregna-1,3,5(10),20-tetraene-3,17 -diol (E-[123I]NIVE)

    International Nuclear Information System (INIS)

    Rijks, Leonie J.M.; Bos, Jan C. van den; Doremalen, Peter A.P.M. van; Boer, Gerard J.; Bruin, Kora de; Doornbos, Tamme; Vekemans, Jozef A.J.M.; Posthumus, Maarten A.; Janssen, Anton G.M.; Royen, Eric A. van

    1998-01-01

    We have synthesized and evaluated E-11β-nitrato-17α-iodovinylestradiol (E-NIVE; E-3c) and its 123 I-labelled form, as a new potential radioligand for imaging of estrogen receptor (ER)-positive human breast tumors. E-[ 123 I]NIVE was prepared by stereospecific iododestannylation of the E-tri-n-butylstannylvinyl precursor (E-2c), obtained from reaction of 11β-nitrato-estrone (8) with E-tributylstannylvinyllithium. In competitive binding studies, E-NIVE proved to have high binding affinity for both the rat and the human ER (K i 280-730 pM), without significant binding to human sex hormone binding globulin. Distribution studies in normal and mammary tumor-bearing rats showed specific ER-mediated uptake of E-[ 123 I]NIVE in the estrogen target tissues, i.e., uterus, ovaries, pituitary, and hypothalamus, but not in the mammary tumors. Selective retention in these target tissues, including tumor tissue, resulted in significant increases over time for the target tissue-to-muscle uptake ratios, but not for the target tissue-to-fat uptake ratios. The tumor-to-fat uptake ratio even appeared constantly below 1. In the primary estrogen target tissues, E-[ 123 I]NIVE displayed high specific ER-mediated uptake and retention, which resulted in moderate target-to-nontarget tissue uptake ratios. In contrast, in tumor tissue, E-[ 123 I]NIVE uptake appeared to be rather low and not ER-specific. As a consequence, E-[ 123 I]NIVE appears to be a less favorable radioligand for ER imaging in breast cancer than the previously studied stereoisomers of 11β-methoxy-17α-[ 123 I]iodovinylestradiol (E- and Z-[ 123 I]MIVE; [ 123 I]E- and [ 123 I]Z-3b).

  19. Synthesis, estrogen receptor binding, and tissue distribution of a new iodovinylestradiol derivative (17{alpha},20E)-21-[{sup 123}I]iodo-11{beta}-nitrato-19-norpregna-1,3,5(10),20-te= traene-3,17 -diol (E-[{sup 123}I]NIVE)

    Energy Technology Data Exchange (ETDEWEB)

    Rijks, Leonie J.M.; Bos, Jan C. van den; Doremalen, Peter A.P.M. van; Boer, Gerard J.; Bruin, Kora de; Doornbos, Tamme; Vekemans, Jozef A.J.M.; Posthumus, Maarten A.; Janssen, Anton G.M.; Royen, Eric A. van

    1998-05-01

    We have synthesized and evaluated E-11{beta}-nitrato-17{alpha}-iodovinylestradiol (E-NIVE; E-3c) and its {sup 123}I-labelled form, as a new potential radioligand for imaging of estrogen receptor (ER)-positive human breast tumors. E-[{sup 123}I]NIVE was prepared by stereospecific iododestannylation of the E-tri-n-butylstannylvinyl precursor (E-2c), obtained from reaction of 11{beta}-nitrato-estrone (8) with E-tributylstannylvinyllithium. In competitive binding studies, E-NIVE proved to have high binding affinity for both the rat and the human ER (K{sub i} 280-730 pM), without significant binding to human sex hormone binding globulin. Distribution studies in normal and mammary tumor-bearing rats showed specific ER-mediated uptake of E-[{sup 123}I]NIVE in the estrogen target tissues, i.e., uterus, ovaries, pituitary, and hypothalamus, but not in the mammary tumors. Selective retention in these target tissues, including tumor tissue, resulted in significant increases over time for the target tissue-to-muscle uptake ratios, but not for the target tissue-to-fat uptake ratios. The tumor-to-fat uptake ratio even appeared constantly below 1. In the primary estrogen target tissues, E-[{sup 123}I]NIVE displayed high specific ER-mediated uptake and retention, which resulted in moderate target-to-nontarget tissue uptake ratios. In contrast, in tumor tissue, E-[{sup 123}I]NIVE uptake appeared to be rather low and not ER-specific. As a consequence, E-[{sup 123}I]NIVE appears to be a less favorable radioligand for ER imaging in breast cancer than the previously studied stereoisomers of 11{beta}-methoxy-17{alpha}-[{sup 123}I]iodovinylestradiol (E- and Z-[{sup 123}I]MIVE; [{sup 123}I]E- and [{sup 123}I]Z-3b)

  20. An Integrated Computational Approach to Binding Theory

    OpenAIRE

    Bonato, Roberto

    2006-01-01

    thèse en cotutelle franco italienne; bourse régionale de la Vénétie; Pronouns play a decisive role in every natural language as the linguistic ele- ments that enable semantic cohesion of a text. Anaphora resolution (that is, the task of recovering in an automatic way the semantic content of pronouns) is therefore both an important theoretical issue and a ma jor technological challenge for any computer application that aims at a ?ner-grained semantic analysis of natural language texts. Binding...