bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment and Recommendations on Factors Contributing to Preanalytical Variability of Urinary Pyridinoline and Deoxypyridinoline
Authors: Vesper Hubert W , Demers Laurence M , Eastell Richard , Garnero Patrick , Kleerekoper Michael , Robins Simon P , Srivastava Apurva K , Warnick G Russell , Watts Nelson B , Myers Gary L 
Published: January 2020

AbstractBackground: Pyridinoline (PYD) and deoxypyridinoline (DPD) are two of the most extensively characterized biochemical bone markers, but the interpretation of results is hampered by biologic and other preanalytical variability. We reviewed factors contributing to preanalytical variation of pyridinium cross-links in urine.Methods: We searched four databases for English-language reports on PYD and/or DPD in urine. Searches were restricted to humans, except for studies of stability, when the search was expanded to other species. The 599 identified articles were supplemented with references from those articles and with articles known to the authors.Results: The mean reported within-day variability was 71% for PYD (range, 57–78%) and 67% for DPD (range, 53–75%). The mean interday variability was 16% for both DPD and PYD (range for PYD, 12–21%; range for DPD, 5–24%). The mean intersubject variabilities across studies were 26% for PYD (range, 12–63%) and 34% for DPD (range, 8–98%) for healthy premenopausal women and 36% (range, 22–61%) and 40%, (range, 27–54%) for postmenopausal women, respectively. Specimen instability and errors in creatinine measurements were additional sources of variability.Conclusions: Intra- and intersubject variability can be reduced by collecting specimens at a specific time of the day and by maintaining similar patient status at each specimen collection regarding factors such as medications and dietary supplements.
Collagen Markers Deoxypyridinoline and Hydroxylysine Glycosides: Pediatric Reference Data and Use for Growth Prediction in Growth Hormone-deficient Children
Authors: Rauch Frank , Georg Mareile , Stabrey Angelika , Neu Christina , Blum Werner F , Remer Thomas , Manz Friedrich , Schoenau Eckhard 
Published: January 2020

AbstractBackground: In children and adolescents, markers of bone and collagen metabolism reflect the dynamics of skeletal growth and development. The aim of this study was to assess the relationship of the urinary collagen markers deoxypyridinoline (DPD) and hydroxylysine (Hyl) and its glycosides [galactosyl-Hyl (Gal-Hyl) and glucosyl-Gal-Hyl] with growth.Methods: Urine samples from 240 apparently healthy children and adolescents (6–19 years; 124 girls) and from 51 prepubertal children with growth hormone (GH) deficiency (3–14 years; 14 girls) were analyzed. Urinary Hyl and its glycosides were quantified by HPLC, and DPD was assessed by chemiluminescence assay. Urinary concentrations of all markers were related to urinary creatinine.Results: Multiple regression analysis revealed that only age and height velocity were independently associated with these markers in healthy children. In GH-deficient patients, the urinary excretion of both analytes after 4 weeks of GH therapy correlated significantly with the height increase during the first treatment year (r = 0.79 for Gal-Hyl; r = 0.70 for DPD; P &lt;0.001 each). In a multivariate linear regression model using Gal-Hyl concentrations at 4 weeks, baseline concentrations of insulin-like growth factor 1 and height velocity after 3 months accounted for 80% of the variability in height gain during the first treatment year. A model using DPD concentrations at 4 weeks, in place of Gal-Hyl concentrations, as well as baseline concentrations of insulin-like growth factor 1 and height velocity after 3 months accounted for 83% of the variability.Conclusions: These urinary bone and collagen markers give some early indication of growth response, but the prediction of an individual marker is too imprecise to serve as a basis for clinical decisions. Markers of bone and collagen metabolism might be more useful as components of multivariate growth prediction models.
Biochemical and Genetic Markers of Iron Status and the Risk of Coronary Artery Disease: An Angiography-based Study
Authors: Bozzini Claudia , Girelli Domenico , Tinazzi Elisa , Olivieri Oliviero , Stranieri Chiara , Bassi Antonella , Trabetti Elisabetta , Faccini Giovanni , Pignatti Pier Franco , Corrocher Roberto 
Published: January 2020

Abstract
Background: Iron may promote coronary atherosclerotic disease (CAD) by increasing lipid peroxidation. Studies on biochemical or genetic markers of body iron stores as risk factors for CAD have yielded conflicting results.
Methods: We studied 849 individuals with a clear-cut definition of the CAD phenotype, i.e., with (CAD; n = 546) or without (CAD-free; n = 303) angiographically documented disease. We determined serum ferritin, as a biochemical estimate of iron stores, and the C282Y mutation in the HFE gene, i.e., the main cause of hemochromatosis in Caucasians. The relationships of ferritin with serum markers of either inflammation [C-reactive protein (CRP)] or lipid peroxidation (malondialdehyde) were also investigated.
Results: Mean ferritin concentrations were slightly higher in CAD vs CAD-free individuals, but this difference disappeared after adjusting for sex and CRP. Ferritin was significantly correlated with CRP (Spearman’s test, ρ = 0.129; P &lt;0.001). Heterozygotes for Cys282Tyr were 4.8% among the CAD group and 6.6% among the CAD-free group (P = 0.26). The prevalence of high concentrations of stored iron, defined as ferritin concentrations above the sex-specific upper quintiles of the control distribution, was also similar in the two groups. There was a higher prevalence of “iron depletion” in CAD-free vs CAD females (20% vs 8.8%, respectively), but this difference disappeared after adjustment for age and other cardiovascular risk factors (odds ratio, 0.66; 95% confidence interval, 0.21–2.08). No differences in iron markers were found in CAD patients with or without myocardial infarction.
Conclusions: Our results do not support a role for biochemical or genetic markers of iron stores as predictors of the risk of CAD or its thrombotic complications.
Molecular Diagnosis of Analbuminemia: A Novel Mutation Identified in Two Amerindian and Two Turkish Families
Authors: Galliano Monica , Campagnoli Monica , Rossi Antonio , Wirsing von König Carl Heinz , Lyon Andrew W , Cefle Kivanc , Yildiz Alaattin , Palanduz Sukru , Ozturk Sukru , Minchiotti Lorenzo 
Published: January 2020

AbstractBackground: Analbuminemia is a rare autosomal recessive disorder in which individuals have little or no circulating albumin, usually the most abundant plasma protein. We describe a new mutation associated with analbuminemia.Methods: We studied four apparently unrelated patients who had congenital analbuminemia: two of Amerindian and two of Turkish origin. The 14 exons and the flanking intron sequences of the albumin gene were amplified by PCR and screened for mutations by single-strand conformational polymorphism and heteroduplex analysis. The mutated DNA fragments were sequenced directly.Results: In all four cases, analbuminemia was caused by the same mutation, an AT deletion at nucleotides 2430–2431, the 91st and 92nd bases of exon 3. This novel defect, named Kayseri, produces a frameshift leading to a premature stop two codons downstream. The predicted translation product would consist of 54 amino acid residues.Conclusions: The AT deletion at nucleotides 2430–2431 is a novel mutation associated with analbuminemia.
Cardiac Troponin T and Creatine Kinase MB Content in Skeletal Muscle of the Uremic Rat
Authors: Fredericks Salim , Murray Joanne F , Carter Nicholas D , Chesser Alistair MS , Papachristou Stavroula , Yaqoob Magdi M , Collinson Paul O , Gaze David , Holt David W 
Published: January 2020

AbstractBackground: The assertion that creatine kinase MB (CK-MB) and the developmental isoforms of cardiac troponin T (cTnT) are expressed by skeletal muscle in some clinical settings is an extrapolation from nonuremic rodent studies. We studied the content of CK-MB and cTnT in skeletal muscle of the renal-insufficient rat.Methods: Skeletal muscles (gastrocnemius) were collected from both five-sixths nephrectomized rats (n = 11) and sham-operated controls (n = 11). cTnT content was analyzed by Elecsys (Roche), immunoblotting, and immunohistochemistry with antibodies M7 and M11-7 (Roche). CK isoenzymes were analyzed electrophoretically.Results: Trace concentrations of cTnT were detected in some of the skeletal muscle samples [controls (3 of 11) and uremic rats (1 of 11)] at concentrations &lt;0.01% of that detected in heart. By contrast, positive staining appeared in both groups with M11-7 by immunoblotting and immunohistochemistry. No immunoreactivity was detected in skeletal muscle using M7 in the immunoblot format, although immunoreactivity was detected by immunohistochemistry in all samples. The median percentages of CK-MB were 6.0% and 4.1% for the skeletal muscle from control and uremic rats, respectively.Conclusion: The detection of cTnT and CK-MB in skeletal muscle does not differ for uremic rats compared with sham-operated controls. cTnT isoforms detected by qualitative methods are not detected with the cTnT immunoassay. Observations with rodents should not necessarily be extrapolated to humans.
Quantitative Measurement of Lipoprotein Particles Containing Both Apolipoprotein AIV and Apolipoprotein B in Human Plasma by a Noncompetitive ELISA
Authors: Ferrer Fanny , Bigot-Corbel Edith , N′Guyen Patrick , Krempf Michel , Bard Jean-Marie 
Published: January 2020

AbstractBackground: A reliable method for plasma would be useful to investigate the role of apolipoprotein (apo) AIV when associated with apo B-containing or triglyceride-rich lipoproteins.Method: We used a sandwich ELISA to quantify lipoprotein B:AIV particles (Lp B:AIVf; lipoproteins containing at least apo B and apo AIV) in plasma. The method used microtiter plates coated with purified anti-apo B immunoglobulins that selectively retained apo B-containing particles. Lipoproteins containing both apo B and apo AIV were distinguished from those containing only apo B by use of a peroxidase-labeled anti-apo AIV antibody. These subspecies were revealed by ABTS® reagent and further quantified by spectrophotometry. Results were expressed in mg/L apo AIV associated with apo B. This method was applied to samples with different cholesterol and triglyceride concentrations.Results: The developed sandwich ELISA method identified and quantified Lp B:AIVf in plasma samples. Within- and between-run CVs were ∼10%, and analytical recoveries were 95–107%. Results were not significantly influenced by addition of triglycerides or by storage at −20 °C (up to 9 months). Under these conditions, plasma Lp B:AIVf concentrations were statistically higher in hypercholesterolemic and mixed hyperlipidemic individuals (53 ± 13 mg/L; P &lt;0.001 and 70 ± 18 mg/L; P &lt;0.001, respectively) than in normolipidemic individuals (43 ± 12 mg/L). Lp B:AIVf concentration appeared to be well correlated with total cholesterol, triglycerides, LDL-cholesterol, and apo B. These results were in contrast to total apo AIV, which was not different between dyslipidemic and normolipidemic individuals.Conclusions: The developed ELISA method for Lp B:AIVf in plasma combines specificity, reliability, and speed. The increase in Lp B:AIVf concentrations in various dyslipidemic states, together with a lack of change in total apo AIV concentrations, suggests a redistribution of apo AIV toward apo B-containing lipoproteins when these lipoproteins accumulate.
Long-Term Analytical Performance of Hemostasis Field Methods as Assessed by Evaluation of the Results of an External Quality Assessment Program for Antithrombin
Authors: Meijer Piet , de Maat Moniek PM , Kluft Cornelis , Haverkate Frits , van Houwelingen Hans C 
Published: January 2020

Abstract
Background: It is important for a laboratory to know the stability of performance of laboratory tests over time. The aim of this study was to adapt from the field of clinical chemistry a method to assess the long-term analytical performance of hemostasis field methods.
Methods: The linear regression model was used to compare the laboratory results with the consensus mean value of a survey. This model was applied to plasma antithrombin activity using the data for 82 laboratories, collected between 1996 and 1999 in the European Concerted Action on Thrombosis (ECAT) external quality assessment program. The long-term total, random, and systematic error were calculated. The variables introduced to define the long-term performance in this model were the long-term analytical CV (LCVa) and the analytical critical difference (ACD), which indicates the minimum difference necessary between two samples measured on a long-term time-scale to consider them statistically significantly different.
Results: The systematic error (bias) ranged from 4.5 to 103 units/L. The random error ranged from 24.4 to 242 units/L. For the majority of the laboratories, random error was the main component (&gt;75%) of the total error. The LCVa, after adjustment for the contribution of the bias, ranged from 2.8% to 48%. The ACD ranged from 78 to 1290 units/L with a median value of 190 units/L. No statistically significant differences were observed for either LCVa or ACD between the two different measurement principles for antithrombin activity based on the inhibition of either thrombin or factor Xa.
Conclusions: This linear regression model is useful for assessing the total error, random error, and bias for hemostasis field methods. The LCVa and ACD for measurement on a long-term time-scale appear to be useful for assessing the long-term analytical performance.
Computer-supported Interpretation of Protein Profiles after Capillary Electrophoresis
Authors: Jonsson Magnus , Carlson Joyce 
Published: January 2020

AbstractBackground: Electrophoretic patterns of proteins in serum/plasma are useful in the diagnosis and evaluation of many diseases. Capillary zone electrophoresis (CZE) allows rapid and automated protein separation and produces digital absorbance data, appropriate for mathematical analysis. We previously demonstrated success in detection of monoclonal immunoglobulins in such a system. This study tests new algorithms to produce rapid standardized computer-supported interpretation of the entire electropherogram.Methods: Data from Beckman Paragon CZE 2000 electropherograms were compared with quantitative protein data from &gt;800 routine clinical samples. Algorithms were designed to produce semiquantitative analyses of major proteins and to define different patterns of inflammation based on the electropherogram.Results: The algorithms produced reliable semiquantitative evaluations of prealbumin, albumin, α1-antitrypsin, haptoglobin, and transferrin, but were less accurate for α1-acid glycoprotein. Some genetic variants of albumin and deficiency variants of α1-antitrypsin were easily recognized. Complex clinical traits such as degree and type of inflammation could be evaluated. When used together with previously developed algorithms addressing immunoglobulins, the new algorithms provide relevant clinical interpretation. Selected outputs indicate the need for reflex testing or evaluation by specialists.Conclusions: Automation of both electrophoresis and interpretation can provide a rapid, inexpensive, standardized analysis that can hopefully improve the diagnostic information and clinical outcome for large groups of patients. It also provides objective criteria for clinical interpretations, to be validated or adjusted in future clinical studies.
Human Tissue Kallikreins: A Family of New Cancer Biomarkers
Authors: Diamandis Eleftherios P , Yousef George M 
Published: January 2020

AbstractKallikreins are a subgroup of the serine protease enzyme family. Until recently, it was thought that the human kallikrein gene family contained only three members. In the past 3 years, the entire human kallikrein gene locus was discovered and found to contain 15 kallikrein genes. Kallikreins are expressed in many tissues, including steroid hormone-producing or hormone-dependent tissues such as the prostate, breast, ovary, and testis. Most, if not all, kallikreins are regulated by steroid hormones in cancer cell lines. There is strong but circumstantial evidence linking kallikreins and cancer. Prostate-specific antigen (PSA; hK3) and, more recently, human glandular kallikrein (hK2) are widely used tumor markers for prostate cancer. Three other kallikreins, hK6, hK10, and hK11, are emerging new serum biomarkers for ovarian and prostate cancer diagnosis and prognosis. Several other kallikreins are differentially expressed at both the mRNA and protein levels in various endocrine-related malignancies, and they have prognostic value. The coexpression of many kallikreins in the same tissues (healthy and malignant) points to the possible involvement of kallikreins in cascade enzymatic pathways. In addition to their diagnostic/prognostic potential, kallikreins may also emerge as attractive targets for therapeutics.
Host Genetic Polymorphism Analysis in Cervical Cancer
Authors: Calhoun Eric S , McGovern Renee M , Janney Carol A , Cerhan James R , Iturria Stephen J , Smith David I , Gostout Bobbie S , Persing David H 
Published: January 2020

AbstractBackground: The natural history of cervical cancer comprises a latency period that probably involves long-term immunologic tolerance of human papillomavirus infection. Identifying host determinants of viral persistence may help to better understand the mechanisms of tolerance and may lead to the development of tests that can allow more focused follow-up of high-risk individuals.Methods: Genotypic frequencies of 12 polymorphic loci in four candidate genes from 127 cervical cancer patients were compared with a control group of 108 female blood donors. Genotypes were determined by PCR amplification and direct sequencing of isolated genomic DNA.Results: The tumor necrosis factor-α (TNFα) −238 polymorphism was significantly underrepresented in cervical cancer patients [heterozygotes (HETs), odds ratio (OR) = 0.33; 95% confidence interval (CI), 0.11–0.96], as was the TNFα −376 polymorphism (P = 0.02; 0% for any variant genotype in cases vs 4.7% in controls). The NRAMP1 3′ untranslated region STP+86 polymorphism also appeared to be inversely associated with cervical cancer, but this result did not reach statistical significance (HET, OR = 0.57; 95% CI, 0.32–1.02). The p53 codon 72 arginine allele showed a suggestive negative association with cervical cancer (HET, OR = 0.49; 95% CI, 0.14–1.63; homozygotes, OR = 0.35; 95% CI, 0.11–1.17). The remaining alleles tested showed no association with cervical cancer.Conclusions: We identified host genetic polymorphisms that may be associated with cervical cancer risk, some of which have been linked to potential functional effects on cellular immune responses or antigen processing. We failed to confirm earlier reports of increased cervical cancer susceptibility in women who harbor the p53 P72R allele. Although our findings support the general hypothesis that host immunogenetic determinants other than class II MHC may be important in the development of cervical cancer, further analysis of the HLA gene cluster comprising the implicated TNFα single-nucleotide polymorphisms will be required to determine whether their association is linkage independent.
Application of a Multigene Reverse Transcription-PCR Assay for Detection of Mammaglobin and Complementary Transcribed Genes in Breast Cancer Lymph Nodes
Authors: Zehentner Barbara K , Dillon Davin C , Jiang Yuqiu , Xu Jiangchun , Bennington Angela , Molesh David A , Zhang XinQun , Reed Steven G , Persing David , Houghton Raymond L 
Published: January 2020

AbstractBackground: Mammaglobin mRNA expression is found in 70–80% of primary and metastatic breast tumor biopsies. The potential breast tumor markers B305D, B726P, and γ-aminobutyrate type A receptor π subunit (GABAπ) complement the expression of mammaglobin. Collectively the expression profile of these four genes could be used as a diagnostic and prognostic indicator for breast cancer.Methods: A multigene reverse transcription-PCR (RT-PCR) assay was established to detect the expression of mammaglobin, GABAπ, B305D, and B726P simultaneously. Specific primers and TaqMan® probes were used to analyze combined mRNA expression profiles in primary breast tumors and metastatic lymph node specimens.Results: The multigene RT-PCR assay detected substantial expression signals in 27 of 27 primary tumor and 50 of 50 metastatic breast lymph node samples. Specificity studies demonstrated no significant expression signal in 27 non-breast cancer lymph nodes, in 22 various healthy tissue samples, or in 14 colon tumor samples.Conclusion: The novel RT-PCR-based assay described here provides a sensitive detection system for disseminated breast tumor cells in lymph nodes. In addition, this multigene assay could also be used to test peripheral blood and bone marrow samples.
Diagnosis and Molecular Monitoring of Acute Promyelocytic Leukemia Using DzyNA Reverse Transcription-PCR to Quantify PML/RARα Fusion Transcripts
Authors: Applegate Tanya L , Iland Harry J , Mokany Elisa , Todd Alison V 
Published: January 2020

AbstractBackground: PML/RARα fusion transcripts provide a readily accessible marker for diagnosis of acute promyelocytic leukemia (APL) and for monitoring response to therapy. Survival rates are improved by therapies guided by such monitoring. We assessed the potential of DzyNA reverse transcription-PCR (RT-PCR) for measurement of PML/RARα fusion transcripts.Methods: Parallel single-tube DzyNA RT-PCR protocols were developed to allow real-time fluorescent quantification of PML/RARα fusion transcripts and a low abundance control transcript, normal BCR. Calibration curves, generated using cell line RNA, allowed estimation of these transcripts in RNA from patients with APL at various stages of the disease.Results: DzyNA RT-PCR calibration curves were linear for both transcripts over a broad range and demonstrated interassay variations of 12% (mean, 658 ng) and 10% (mean, 263 ng), respectively. The protocols detected low concentrations of transcripts and resolved twofold dilutions. PML/RARα mRNA was quantified in 10 patients at diagnosis and in 1 patient over a 7-year period. Monitoring of transcript concentrations effectively reflected the disease course in one patient and demonstrated that an increase in PML/RARα transcripts can be detected 4–6 months before hematologic relapse, with no false-positive results.Conclusion: DzyNA RT-PCR has potential for use in clinical practice as a tool for diagnosis of APL and forsubsequent monitoring of minimal residual disease and detection of molecular relapse.