The Experts below are selected from a list of 5145 Experts worldwide ranked by ideXlab platform
Katsumi Yoshida - One of the best experts on this subject based on the ideXlab platform.
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artifactually elevated serum free thyroxine levels measured by Equilibrium Dialysis in a pregnant woman with familial dysalbuminemic hyperthyroxinemia
Thyroid, 2004Co-Authors: Saeko Hoshikawa, Yoshinori Nakagawa, Kouki Mori, Nobuko Kaise, Sadayoshi Ito, Katsumi YoshidaAbstract:Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant syndrome caused by abnormal albumin with an increased affinity for thyroxine (T4). Two types of mutations in the albumin gene, replacing the normal arginine 218 with a histidine (R218H) or a proline (R218P), have been reported to cause FDH. Here, we report a pregnant Japanese woman with FDH caused by the mutant albumin R218P. She had extremely elevated total T4 levels but normal TSH. While the majority of T4was bound to albumin, T4 binding to thyroxine-binding globulin (TBG) was progressively increased throughout pregnancy. Her infant also had elevated serum T4 but normal thyrotropin (TSH). The presence of a guanine to cytosine transition in the second nucleotide of codon 218 of the albumin gene, resulting in a substitution of proline for the normal arginine (R218P), was revealed in the proband. Serum free thyroxine (FT4) levels were increased when measured with some commercial kits including Equilibrium Dialysis followed by ...
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artifactually elevated serum free thyroxine levels measured by Equilibrium Dialysis in a pregnant woman with familial dysalbuminemic hyperthyroxinemia
Thyroid, 2004Co-Authors: Saeko Hoshikawa, Yoshinori Nakagawa, Kouki Mori, Nobuko Kaise, Sadayoshi Ito, Katsumi YoshidaAbstract:Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant syndrome caused by abnormal albumin with an increased affinity for thyroxine (T4). Two types of mutations in the albumin gene, replacing the normal arginine 218 with a histidine (R218H) or a proline (R218P), have been reported to cause FDH. Here, we report a pregnant Japanese woman with FDH caused by the mutant albumin R218P. She had extremely elevated total T4 levels but normal TSH. While the majority of T4was bound to albumin, T4 binding to thyroxine-binding globulin (TBG) was progressively increased throughout pregnancy. Her infant also had elevated serum T4 but normal thyrotropin (TSH). The presence of a guanine to cytosine transition in the second nucleotide of codon 218 of the albumin gene, resulting in a substitution of proline for the normal arginine (R218P), was revealed in the proband. Serum free thyroxine (FT4) levels were increased when measured with some commercial kits including Equilibrium Dialysis followed by radioimmunoassay (RIA) but not when determined by RIA after ultrafiltration of sera. These results indicate an increased T4 binding to TBG during pregnancy in the patients with FDH. Furthermore, our results suggest that normal serum FT4 determined by Equilibrium Dialysis is not an ultimate standard for the diagnosis of FDH in the patients with the mutant albumin R218P.
Michael Vogeser - One of the best experts on this subject based on the ideXlab platform.
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quantification of free serum cortisol based on Equilibrium Dialysis and isotope dilution liquid chromatography tandem mass spectrometry
Clinical Biochemistry, 2011Co-Authors: Fabian Kirchhoff, Josef Briegel, Michael VogeserAbstract:Abstract Objectives Only unbound serum cortisol is bioactive and protein binding of cortisol is highly variable. Thus, the quantification of free serum cortisol (FSC) is of superior biological relevance compared to total serum cortisol quantification. Consequently, the development of automated routine tests for FSC for endocrine testing is desirable — along the lines of free thyroid hormone measurement. Since the availability of a reliable and matrix-independent method is an important tool for this goal, we have developed a highly standardised mass spectrometric FSC method. Design and methods We used Equilibrium Dialysis (ED) to obtain a protein-free fraction from serum samples. The cortisol content of the dialysate was quantified using isotope-dilution two dimensional liquid chromatography (LCxLC–MS/MS). Results Comprehensive evaluation characterised the method as reliable and robust; using commercially available Dialysis cells, convenient handling was realised. Conclusions The method described in this article can be suggested for the implementation of a reference measurement system for FSC.
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Free serum cortisol: quantification applying Equilibrium Dialysis or ultrafiltration and an automated immunoassay system.
Clinical chemistry and laboratory medicine, 2007Co-Authors: Michael Vogeser, Patrick Möhnle, Josef BriegelAbstract:Background: Quantification of bioactive, free serum cortisol concentrations can characterize adrenocortical function more appropriately compared to total serum cortisol measurement. Ultrafiltration or Equilibrium Dialysis of serum samples allow direct measurement of free serum cortisol concentrations but respective methods have poorly been validated so far. The aim of our study was to investigate the analytical performance of free serum cortisol measurement employing Equilibrium Dialysis and ultrafiltration. Methods: Two commercially available ultrafiltration devices and self-assembled Dialysis cells, respectively, were studied. Cortisol was quantified in filtrate or dialysate using an automated immunoassay system. Using two serum pools, the inter-assay coefficient of variation was determined for the three methods and a method comparison was performed. Results: Inter-assay coefficients of variation (n=10) between 3.2% and 14.8% were observed in the imprecision study. Method comparison demonstrated close agreement between free serum cortisol results obtained by ultrafiltration and Equilibrium Dialysis, respectively (Equilibrium Dialysis = 1.2x ultrafiltration+3.9 nmol/L; r=0.99; n=35). Conclusions: Direct quantification of free serum cortisol after Equilibrium Dialysis or ultrafiltration of the samples offers acceptable reproducibility and results in close agreement can be obtained. Both methods can potentially be introduced into a routine laboratory setting.
Saeko Hoshikawa - One of the best experts on this subject based on the ideXlab platform.
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artifactually elevated serum free thyroxine levels measured by Equilibrium Dialysis in a pregnant woman with familial dysalbuminemic hyperthyroxinemia
Thyroid, 2004Co-Authors: Saeko Hoshikawa, Yoshinori Nakagawa, Kouki Mori, Nobuko Kaise, Sadayoshi Ito, Katsumi YoshidaAbstract:Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant syndrome caused by abnormal albumin with an increased affinity for thyroxine (T4). Two types of mutations in the albumin gene, replacing the normal arginine 218 with a histidine (R218H) or a proline (R218P), have been reported to cause FDH. Here, we report a pregnant Japanese woman with FDH caused by the mutant albumin R218P. She had extremely elevated total T4 levels but normal TSH. While the majority of T4was bound to albumin, T4 binding to thyroxine-binding globulin (TBG) was progressively increased throughout pregnancy. Her infant also had elevated serum T4 but normal thyrotropin (TSH). The presence of a guanine to cytosine transition in the second nucleotide of codon 218 of the albumin gene, resulting in a substitution of proline for the normal arginine (R218P), was revealed in the proband. Serum free thyroxine (FT4) levels were increased when measured with some commercial kits including Equilibrium Dialysis followed by ...
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artifactually elevated serum free thyroxine levels measured by Equilibrium Dialysis in a pregnant woman with familial dysalbuminemic hyperthyroxinemia
Thyroid, 2004Co-Authors: Saeko Hoshikawa, Yoshinori Nakagawa, Kouki Mori, Nobuko Kaise, Sadayoshi Ito, Katsumi YoshidaAbstract:Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant syndrome caused by abnormal albumin with an increased affinity for thyroxine (T4). Two types of mutations in the albumin gene, replacing the normal arginine 218 with a histidine (R218H) or a proline (R218P), have been reported to cause FDH. Here, we report a pregnant Japanese woman with FDH caused by the mutant albumin R218P. She had extremely elevated total T4 levels but normal TSH. While the majority of T4was bound to albumin, T4 binding to thyroxine-binding globulin (TBG) was progressively increased throughout pregnancy. Her infant also had elevated serum T4 but normal thyrotropin (TSH). The presence of a guanine to cytosine transition in the second nucleotide of codon 218 of the albumin gene, resulting in a substitution of proline for the normal arginine (R218P), was revealed in the proband. Serum free thyroxine (FT4) levels were increased when measured with some commercial kits including Equilibrium Dialysis followed by radioimmunoassay (RIA) but not when determined by RIA after ultrafiltration of sera. These results indicate an increased T4 binding to TBG during pregnancy in the patients with FDH. Furthermore, our results suggest that normal serum FT4 determined by Equilibrium Dialysis is not an ultimate standard for the diagnosis of FDH in the patients with the mutant albumin R218P.
Kevin R. Oldenburg - One of the best experts on this subject based on the ideXlab platform.
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development of a high throughput Equilibrium Dialysis method
Journal of Pharmaceutical Sciences, 2001Co-Authors: Ilona Kariv, Kevin R. OldenburgAbstract:Abstract The identification of large numbers of biologically active chemical entities during high throughput screening (HTS) necessitates the incorporation of new strategies to identify compounds with drug‐like properties early during the lead prioritization and development processes. One of the major steps in lead prioritization is an assessment of compound binding to plasma proteins, because it affects both the pharmacokinetics and pharmacodynamics of the compound in vivo . Equilibrium Dialysis is the preferred method to determine the free drug fraction, because it is less susceptible to experimental artifacts. However, even low‐volume standard Equilibrium Dialysis is currently not amenable to the HTS format. Those considerations dictate the development of a high throughput Equilibrium Dialysis device, without compromising the analytical quality of the data. The present paper demonstrates successful development of a 96‐well format Equilibrium Dialysis plate. Plasma protein binding of three drugs, propranolol, paroxetine, and losartan, with low, intermediate, and high binding properties, respectively, were chosen for assay validation. The data indicate that the apparent free fraction obtained by this method correlates with the published values determined by the traditional Equilibrium Dialysis techniques. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:580–587, 2001
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Development of a high throughput Equilibrium Dialysis method
Journal of pharmaceutical sciences, 2001Co-Authors: Ilona Kariv, Hong Cao, Kevin R. OldenburgAbstract:The identification of large numbers of biologically active chemical entities during high throughput screening (HTS) necessitates the incorporation of new strategies to identify compounds with drug-like properties early during the lead prioritization and development processes. One of the major steps in lead prioritization is an assessment of compound binding to plasma proteins, because it affects both the pharmacokinetics and pharmacodynamics of the compound in vivo. Equilibrium Dialysis is the preferred method to determine the free drug fraction, because it is less susceptible to experimental artifacts. However, even low-volume standard Equilibrium Dialysis is currently not amenable to the HTS format. Those considerations dictate the development of a high throughput Equilibrium Dialysis device, without compromising the analytical quality of the data. The present paper demonstrates successful development of a 96-well format Equilibrium Dialysis plate. Plasma protein binding of three drugs, propranolol, paroxetine, and losartan, with low, intermediate, and high binding properties, respectively, were chosen for assay validation. The data indicate that the apparent free fraction obtained by this method correlates with the published values determined by the traditional Equilibrium Dialysis techniques.
Jacobus P J Ungerer - One of the best experts on this subject based on the ideXlab platform.
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free cortisol method comparison ultrafiltation Equilibrium Dialysis tracer dilution tandem mass spectrometry and calculated free cortisol
Clinica Chimica Acta, 2011Co-Authors: Carel J Pretorius, John Galligan, Brett Mcwhinney, Scott Briscoe, Jacobus P J UngererAbstract:Abstract Background Free cortisol (FC) can be calculated from measurements of total cortisol and binding proteins or measured after mechanical separation of unbound and bound fractions by Equilibrium Dialysis or ultrafiltration. FC can then be measured indirectly by 3 H-cortisol dilution or directly by immunologic or tandem mass spectrometry assays. Methods We compared FC measured with ultra high performance liquid chromatography – tandem mass spectrometry (UHPLC MS/MS) with 3 H-cortisol dilution in ultrafiltrates and dialysates and also with calculated FC (Coolens equation). An adult FC reference interval was established. Results The UHPLC MS/MS and 3 H-cortisol dilution methods were non-linearly related (Cusum linearity test p R 2 = 0.984). FC calculated with Coolens equation agreed with the UHPLC MS/MS method. Impurity of 3 H-cortisol and non-specific adsorption were excluded as causes on non-linearity. Ultrafiltration was linearly related to Equilibrium Dialysis, simpler to perform and more repeatable. A gender non-specific FC reference interval of 2.1–19.1 nmol/L was established. Conclusions In view of the non-linearity between measuring techniques and the variability of reported reference ranges, care should be exercised in adopting a reference range. The ultrafiltration UHPLC MS/MS method we described is robust and suitable for use in a routine laboratory.