Abstract：
INTRODUCTION:Parathyroid hormone-related peptide (PTHrP) is involved in activating pathways, allowing tumor cells to form bone metastases. Measurement of PTHrP is used for the diagnosis and clinical management of patients suspected of hypercalcemia of malignancy. We developed an LC-MS/MS method for measuring PTHrP, established sex-specific reference intervals, and assessed the method's performance. METHODS:PTHrP was enriched from plasma samples with rabbit polyclonal anti-PTHrP antibody conjugated to magnetic beads. Enriched PTHrP was digested with trypsin, and PTHrP-specific tryptic peptide was analyzed with 2-dimensional LC-MS/MS in multiple reaction monitoring mode. RESULTS:The lower limit of quantification was 0.6 pmol/L, and the upper limit of linearity was 600 pmol/L. Total imprecision was <10%. Very poor agreement was observed with the RIA (n = 207; Deming regression RIA = 0.059 × LC-MS/MS - 1.8, r = 0.483; Sy|x = 3.9). Evaluation of the clinical performance of the assay using samples from patients with and without hypercalcemia (n = 199) resulted in an area under the ROC curve of 0.874. In sets of consecutively analyzed routine samples of patients assessed for hypercalcemia, the PTHrP positivity rate by RIA (n = 1376) was 1.9%, and 26.6% by LC-MS/MS (n = 1705). Concentrations were below the lower limit of quantification in 95.6% of the samples by RIA and 2.0% by LC-MS/MS. CONCLUSIONS:PTHrP is a normal constituent in circulating blood and its concentrations are substantially underestimated by commercial RIAs, causing false-negative results in samples from patients suspected of hypercalcemia. Our observations suggest a link between increased concentrations of PTHrP in postmenopausal women with low body mass index and increased incidence of osteoporosis.
journal_name
Clin Chemjournal_title
Clinical chemistryauthors
Kushnir MM,Rockwood AL,Strathmann FG,Frank EL,Straseski JA,Meikle AWdoi
10.1373/clinchem.2015.244012subject
Has Abstractpub_date
2016-01-01 00:00:00pages
218-26issue
1eissn
0009-9147issn
1530-8561pii
clinchem.2015.244012journal_volume
62pub_type
杂志文章abstract：:We present a simple method for subclass typing of IgG paraproteins, with which we have demonstrated a large number of paraproteins that were undetected by conventional immunofixation techniques. The types and distribution of IgG subclass paraproteins were analyzed in 92 human sera in which IgG paraproteins had been de...
journal_title：Clinical chemistry
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doi：
更新日期：1995-10-01 00:00:00
abstract：BACKGROUND:Myeloperoxidase (MPO) is a biomarker of inflammation and oxidative stress produced by neutrophils, monocytes, and endothelial cells. Concentrations of MPO predict mortality in patients with chronic heart failure. This study sought to investigate the diagnostic accuracy and prognostic value of MPO in patients...
journal_title：Clinical chemistry
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doi：10.1373/clinchem.2009.142257
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abstract：:Proteinuria, long recognized as a sign of renal disease, is a common laboratory abnormality in children and adults. Proteinuria may be transient or persistent; when persistent, the cause must be determined. Proteinuria may be primarily glomerular or tubular in origin. Glomerular proteinuria is usually an important con...
journal_title：Clinical chemistry
pub_type： 杂志文章,评审
doi：
更新日期：1989-05-01 00:00:00
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journal_title：Clinical chemistry
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doi：10.1373/clinchem.2004.039891
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journal_title：Clinical chemistry
pub_type： 杂志文章,评审
doi：10.1373/clinchem.2015.239491
更新日期：2016-01-01 00:00:00
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journal_title：Clinical chemistry
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doi：
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journal_title：Clinical chemistry
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doi：
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journal_title：Clinical chemistry
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doi：
更新日期：1999-12-01 00:00:00
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journal_title：Clinical chemistry
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doi：
更新日期：1983-08-01 00:00:00
abstract：BACKGROUND:Consideration of circulating biomarkers for risk stratification in heart failure (HF) is recommended, but the influence of atrial fibrillation (AF) on prognostic performance of many markers is unclear. We investigated the influence of AF on the prognostic performance of circulating biomarkers in HF. METHODS...
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doi：10.1093/clinchem/hvaa287
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journal_title：Clinical chemistry
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doi：
更新日期：1989-07-01 00:00:00
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journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1995-02-01 00:00:00
abstract：:The IFCC-recommended procedure for aspartate aminotransferase (EC 2.6.1.1) was adapted to the centrifugal analyzer and evaluated during five years. The main hindrance to widespread use of the recommended method is the need for pre-incubation with pyridoxal phosphate. The present method includes a 10-min pre-incubation...
journal_title：Clinical chemistry
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doi：
更新日期：1981-01-01 00:00:00
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journal_title：Clinical chemistry
pub_type： 杂志文章
doi：10.1373/clinchem.2006.074021
更新日期：2007-02-01 00:00:00
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journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
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journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1987-08-01 00:00:00
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journal_title：Clinical chemistry
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doi：
更新日期：1986-08-01 00:00:00
abstract：:The human ras gene plays a fundamental role in the transduction of extracellular signals to the nucleus, thereby regulating cell growth and differentiation. Point mutations in the ras gene convert it into a transforming oncogene that has been found in many solid and hematologic malignancies. We describe a rapid and se...
journal_title：Clinical chemistry
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doi：
更新日期：1994-05-01 00:00:00
abstract：BACKGROUND:Human iron status is influenced by environmental and genetic factors. We hypothesized that the genetic polymorphism of haptoglobin (Hp), a hemoglobin-binding plasma protein, could affect iron status. METHODS:Reference values of serum iron status markers were compared according to Hp phenotypes (Hp 1-1, Hp 2...
journal_title：Clinical chemistry
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doi：
更新日期：2000-10-01 00:00:00
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doi：10.1373/clinchem.2012.191072
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journal_title：Clinical chemistry
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doi：
更新日期：1987-04-01 00:00:00
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doi：10.1373/clinchem.2017.277517
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journal_title：Clinical chemistry
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doi：10.1373/clinchem.2004.032763
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journal_title：Clinical chemistry
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doi：
更新日期：1990-07-01 00:00:00
abstract：:We describe a new and specific method for measurement of lecithin palmitic acid in amniotic fluid. Dipalmitoyl lecithin, the major alveolar surfactant, has previously been estimated by measuring the lecithin-sphingomyelin ratio, total lecithin, total phospholipid phosphorus, and (or) total palmitic acid. Our method is...
journal_title：Clinical chemistry
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doi：
更新日期：1977-01-01 00:00:00
abstract：BACKGROUND:Published literature was systematically reviewed to determine the diagnostic accuracy of new protein markers of acute coronary syndromes (ACS) in symptomatic outpatients at low risk of ACS and related complications comparable to patients evaluated in emergency department chest pain units. METHODS:Studies we...
journal_title：Clinical chemistry
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abstract：BACKGROUND:Although microRNAs (miRNAs) play essential roles in spermatogenesis, little is known about seminal plasma miRNAs in infertile men. We investigated the profile of seminal plasma miRNAs in infertile men to identify miRNAs that are altered in infertility; we then evaluated their diagnostic value. METHODS:Semin...
journal_title：Clinical chemistry
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doi：10.1373/clinchem.2011.169714
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journal_title：Clinical chemistry
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doi：
更新日期：1991-12-01 00:00:00
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journal_title：Clinical chemistry
pub_type： 杂志文章
doi：
更新日期：1978-12-01 00:00:00
