Abstract：
BACKGROUND:PS-341, a selective inhibitor of the proteasome, currently is under evaluation as an anticancer agent in multiple phase I clinical trials. In animal-model studies, PS-341 was rapidly removed from the vascular compartment and distributed widely, quickly approaching the limits of detection. An accurate pharmacodynamic assay has been developed as an alternative or complement to pharmacokinetic measurements. METHODS:Fluorogenic kinetic assays for both the chymotryptic and tryptic activities of the proteasome have been optimized for both whole blood and blood cells. Using the ratio of these activities and the catalytic mechanism of the proteasome, we developed a novel method of calculating percentage of inhibition, using two structurally unrelated inhibitors (PS-341 and lactacystin). RESULTS:This ratio method was demonstrated to be sensitive (detection limit of 13% inhibition with 10 microgram of cell lysate), specific to the proteasome (PS-341 provides >98% inhibition), accurate (112% analyte recovery), and precise (0% +/- 5% inhibition at 0 nmol/L PS-341 and 74.5% +/- 1.7% inhibition at 200 nmol/L PS-341). Using these assays, we found that both erythrocytes and leukocytes contain proteasome at 3 micromol/L. Pharmacodynamic results for PS-341 obtained from the whole-blood ratio method were comparable to those using leukocytes determined by another method. CONCLUSIONS:The described assay provides a reliable method for studying the pharmacodynamics of proteasome inhibitors and is now in use in concurrent phase I clinical trials with PS-341.
journal_name
Clin Chemjournal_title
Clinical chemistryauthors
Lightcap ES,McCormack TA,Pien CS,Chau V,Adams J,Elliott PJsubject
Has Abstractpub_date
2000-05-01 00:00:00pages
673-83issue
5eissn
0009-9147issn
1530-8561journal_volume
46pub_type
杂志文章abstract：BACKGROUND:The Dutch project "Calibration 2000" aims at harmonization of laboratory results via calibration by development of matrix-based secondary reference materials. We considered the selection, preparation, and characterization of 34 potential reference materials (PRMs). METHODS:Sixteen PRMs were prepared either ...
journal_title：Clinical chemistry
pub_type： 杂志文章,多中心研究
doi：
更新日期：2002-09-01 00:00:00
abstract：:We studied the relationship between serum erythropoietin (EPO) concentration and iron status in 67 patients undergoing chronic hemodialysis. Serum concentrations of EPO were measured by RIA with recombinant human EPO. The geometric mean of the serum EPO concentration was 10.9 int. units/L (mean +/- SD range = 7.8 - 15...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1992-02-01 00:00:00
abstract：BACKGROUND:Non-(1-84) parathyroid hormone (PTH) fragments are large C-terminal fragments of PTH with a partially preserved N-terminal structure. They differ from other C-terminal PTH fragments, which do not have an N-terminal structure and do not react in intact PTH assays. We aimed to identify the minimal N-terminal s...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：10.1373/clinchem.2004.040485
更新日期：2005-01-01 00:00:00
abstract：:A continuous-monitoring method for measuring acid phosphatase activity with alpha-naphthyl phosphate as the substrate was critically evaluated and modified. Using partially purified prostatic acid phosphatase, we show that certain conditions for the assay must be satisfied to ensure linearity. These conditions include...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1976-12-01 00:00:00
abstract：:Detection and characterization of small IgM paraproteins by immunoelectrophoresis are often difficult because of (a) slow diffusion of the macromolecular immunoglobulin, and (b) the obscuring of the light chain, especially kappa, by the light chains of background polyclonal immunoglobulin (the "umbrella effect"). Vari...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:Throughout the 1970s, controversy centered both on immunoassay "sensitivity" per se and on the relative sensitivities of labeled antibody (Ab) and labeled analyte methods. Our theoretical studies revealed that RIA sensitivities could be surpassed only by the use of very high-specificity nonisotopic labels in "noncompe...
journal_title：Clinical chemistry
pub_type： 杂志文章,评审
doi：
更新日期：1991-11-01 00:00:00
abstract：:We report the adaptation of four radioassays to the prototype of an automated radioimmunoassay system ("Centria," Union Carbide). The system consists of three integrated modules: (a) an automated pipettor, which dispenses samples and reagents; (b) the key module, an incubator/separator, in which centrifugal force is u...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1975-08-01 00:00:00
abstract：:We describe a simple and convenient method for processing small amounts of tissue samples for trace-metal measurements by atomic absorption spectrometry, by use of a modified Parr microwave digestion bomb. Digestion proceeds rapidly (less than or equal to 90 s) in a sealed Teflon-lined vessel that eliminates contamina...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1989-03-01 00:00:00
abstract：BACKGROUND:First introduced into clinical microbiology laboratories in Europe, MALDI-TOF MS is being rapidly embraced by laboratories around the globe. Although it has multiple applications, its widespread adoption in clinical microbiology relates to its use as an inexpensive, easy, fast, and accurate method for identi...
journal_title：Clinical chemistry
pub_type： 杂志文章,评审
doi：10.1373/clinchem.2014.221770
更新日期：2015-01-01 00:00:00
abstract：:In this immunoenzymatic assay for human lutropin (hLH) we used bi-specific antibodies (BiAbs) obtained from the fusion of two hybridomas producing antibodies to beta-D-galactosidase and hLh. The BiAb complexed with the enzyme beta-D-galactosidase was used as tracer in a double-determinant assay. We compared the assay ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：:Optimal reaction conditions for assaying human lactate dehydrogenase pyruvate-to-lactate were determined for isoenzymes 1 and 5 at 25, 30, and 37 degrees C. Three of the nine different buffers examined--imidazole, triethanolamine, and N-tris(hydroxymethyl)-methyl-2-aminoethane sulfonic acid--are satisfactory. Beta-NAD...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1978-02-01 00:00:00
abstract：:A convenient screening procedure for presence of drugs of abuse in urine consists of two steps: adsorption of the drugs from urine onto a paper loaded with cation-exchange resin and detection of the adsorbed drugs by direct radioimmunoassay. The first step can be performed in the field, the second in a central laborat...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1977-10-01 00:00:00
abstract：:We have reported (Clin Chem 29: 42-44, 1983) that prestaining with Remazol Brilliant Blue permits direct visualization of serum components on disc electrophoresis, and apparently purifies the proteins well. Here we have cut out the bands corresponding to the prestained albumin and transferrin after disc electrophoresi...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1984-07-01 00:00:00
abstract：BACKGROUND:Evidence suggests that systemic inflammation may adversely impact HDL function. In this study we sought to evaluate the independent and incremental predictive performance of GlycA-a novel serum inflammatory biomarker that is an aggregate measure of enzymatically glycosylated acute phase proteins-and HDL subc...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：10.1373/clinchem.2016.261636
更新日期：2017-01-01 00:00:00
abstract：BACKGROUND:Small RNAs are key players in the regulation of gene expression and differentiation. However, many different classes of small RNAs (sRNAs) have been described with distinct biogenesis pathways and, as a result, with different biochemical properties. To analyze sRNAs by deep sequencing, complementary DNA synt...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：10.1373/clinchem.2019.305045
更新日期：2019-12-01 00:00:00
abstract：:The manual Reference Method of the Centers for Disease Control for serum iron (CDC/RM/Fe) and a semiautomated adaptation of it were used to evaluate two working methods: one, a detergent solubilization procedure for the Roche Cobas-Bio analyzer, the other, the Kodak Ektachem 700 procedure, based on dry-film technology...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
abstract：BACKGROUND:An accurate determination of the major HFE mutation (C282Y), which is associated with hereditary hemochromatosis, is important in diagnosis and risk assessment for this disease. We report a single-tube high-throughput PCR method for the detection of C282Y. METHODS:We combined three previously described prin...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：2000-10-01 00:00:00
abstract：BACKGROUND:Determinations of certain forms of prostate-specific antigen (PSA) have been shown to increase the specificity for prostate cancer (PCa). One such variant, proteolytically active PSA, is a potentially useful tumor marker, but it is not specifically recognized by antibodies. Using phage display libraries, we ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：10.1373/clinchem.2003.026146
更新日期：2004-01-01 00:00:00
abstract：:We describe the interlaboratory testing of a candidate Reference Method (Part I) for uric acid in serum. The method is based on the ultrasound spectrophotometric quantitation of uric acid before and after incubation with uricase. A comprehensive investigation involving 12 laboratories was organized to document the tra...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1982-02-01 00:00:00
abstract：:Numerous xenobiotics regulate cellular functions by altering transcription of target genes. Use of sensitive and specific biomarkers based on gene transcript levels may help clarify the shape of the dose-response curve in the low-dose region associated with human exposures to environmental concentrations of chemicals....
journal_title：Clinical chemistry
pub_type： 杂志文章,评审
doi：
更新日期：1995-12-01 00:00:00
abstract：:In the Prospective Cardiovascular Münster (PROCAM) study, serum lipoprotein(a) [Lp(a)] and its relationship to pro- and anticoagulatory as well as fibrinolytic indices were determined in a large group of employees: 864 men (m) and 373 women (f), ages 16-65 years. Univariate statistical analysis showed Lp(a) concentrat...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:Owing to increased enzymatic hydrolysis of glutamine, additional ammonia is formed in blood and plasma specimens with increased gamma-glutamyltransferase activity (gamma-GT, EC 2.3.2.2.). The close correlation between gamma-GT and glutaminase (EC 3.5.1.2) activities (r = 0.97) in plasma, the inhibition with 6-diazo-5-...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1990-08-01 00:00:00
abstract：:The historical development of a charitable children's hospital and the evolution of its clinical laboratory are presented. With the appearance of practical quantitative blood chemistry tests in the period between the two World Wars, applications to pediatrics were hampered by the need for ultramicro procedures then un...
journal_title：Clinical chemistry
pub_type： 历史文章,杂志文章
doi：
更新日期：2000-07-01 00:00:00
abstract：:We detected increased concentrations of lipoperoxidation products, as malondialdehyde, in the serum of an infant with classic hemolytic-uremic syndrome. The concentrations declined when peritoneal dialysis was initiated and eventually returned to normal after clinical recovery. Our observation adds to the existing bod...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1988-11-01 00:00:00
abstract：:An oligonucleotide "melting" procedure was developed whereby we can monitor for a sequence heterogeneity in the gene for apolipoprotein E production. Two oligonucleotides were synthesized, one recognizing the common epsilon 3 allele but not the common epsilon 2 allele, the other recognizing the epsilon 2 allele but no...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1986-07-01 00:00:00
abstract：:Endotoxin, the lipopolysaccharide cell wall constituent of Gram-negative bacteria, produces symptoms of the Gram-negative sepsis syndrome. By measuring endotoxin in blood from septic patients it may be possible to select a subpopulation of patients in which mortality can be prevented by treatment with anti-endotoxin a...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:We evaluated a new, simple, enzymatic kinetic method from Wako Chemicals GmbH in comparison with a kinetic Jaffé method by using isotope dilution-mass spectrometry (ID-MS) as a reference method. An ID-MS-calibrated serum standard was used. Both the enzymatic and the Jaffé method correlated well with ID-MS, except for ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
abstract：BACKGROUND:Pompe disease (PD) is the first lysosomal storage disorder to be added to the Recommended Uniform Screening Panel for newborn screening. This condition has a broad phenotypic spectrum, ranging from an infantile form (IOPD), with severe morbidity and mortality in infancy, to a late-onset form (LOPD) with vari...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：10.1373/clinchem.2016.259036
更新日期：2017-04-01 00:00:00
abstract：:Because of uncertainty as to the molecular weight of transferrin, a previous comparison [Von der Heul et al., Clin. Chim. Acta 38, 347 (1972)] between transferrin content of serum and total iron-binding capacity cannot be definitive. We found a conversion factor for expressing the maximum amount of iron bound by 1 mg ...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1975-07-01 00:00:00
abstract：:Ireport a detailed series of microcalorimetric measurement of glucose concentrations in five reference samples of serum. The method utilized (a) calibration in the actual medium of analysis and (b) a correction for interferences owing to the nonspecificity of the enzyme hexokinase. The microcalorimetric results are co...
journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1976-10-01 00:00:00
