bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Patterns of Bone Turnover in Relation to Bone Pain and Disease Extent in Bone in Cancer Patients with Skeletal Metastases
Authors: Berruti Alfredo , Dogliotti Luigi , Gorzegno Gabriella , Torta Mirella , Tampellini Marco , Tucci Marcello , Cerutti Stefania , Mosca Frezet Massimo , Stivanello Michela , Sacchetto Giovanna , Angeli Alberto 
Published: January 2020

AbstractBackground: The alteration of the bone microenvironment as a consequence of skeletal metastases is poorly understood. The aim of this study was to search for patterns of bone markers in relation to primary tumor type, bone pain, and number of sites involved in patients with bone metastases.Methods: We studied 323 patients with bone metastases from various primary malignancies. We sequentially measured the serum concentrations of bone alkaline phosphatase [by an electrophoretic technique (BALP)], carboxy-terminal telopeptide of type I collagen (ICTP), calcium (CaS), intact parathyroid hormone (PTH), and the fasting urinary excretion of calcium (Ca:Cr). Immunoradiometric serum bone alkaline phosphatase (I-BALP) and urinary excretion of deoxypyridinoline (DPYD) were also assessed in the 175 cases. Data were analyzed as a function of bone pain (assessed by a validated pain questionnaire), the number of radiographically confirmed sites of bone involvement, and the most frequent primary tumor types: breast cancer (BC; 124 patients), prostate cancer (PC; 90 patients), and non-small cell lung cancer (LC; 49 patients).Results: Serum BALP and I-BALP correlated with the number of radiologically identified blastic bone lesions. BALP and I-BALP were more frequently increased in PC (72% for both measurements) than in BC (50% and 60%, respectively) or LC (3% and 5%, respectively; P &lt;0.001 for BALP and P = 0.001 for I-BALP). ICTP and DPYD values did not differ among PC, BC, and LC, but they did show a direct relationship with the disease extent in bone (P &lt;0.001). CaS and Ca:Cr did not vary significantly according to the bone tumor burden. Bone pain directly correlated with ICTP (P &lt;0.001), DPYD (P = 0.002), CaS (P &lt;0.002), and Ca:Cr (P = 0.001), whereas the relationship was inverse for serum PTH (P = 0.002). When patients were stratified according to the primary tumor, ICTP correlated with the bone pain in all subsets (P &lt;0.005, &lt;0.005, and &lt;0.001 for BC, PC, and LC, respectively), as did CaS and Ca:Cr in LC patients (P = 0.01 and 0.02, respectively) but not in PC and BC patients.Conclusions: The patterns of bone turnover markers differ among the primary tumor types. Both resorption and formation markers reflect the number of radiographically identified sites of bone metastases, whereas resorption markers and serum calcium but not formation markers correlate with bone pain.
Structural Investigations of a New Familial Dysalbuminemic Hyperthyroxinemia Genotype
Authors: Petersen Charles E , Ha Chung-Eun , Harohalli Krishna , Park David S , Feix Jimmy B , Isozaki Osamu , Bhagavan Nadhipuram V 
Published: January 2020

AbstractBackground: In a previous study, we found that the amino acid substitution R218H in human serum albumin (HSA) was the cause of familial dysalbuminemic hyperthyroxinemia (FDH) in several Caucasian patients. Subsequently the substitution R218P was shown to be the cause of FDH in several members of a Japanese family. This study attempts to resolve discrepancies in the only other study of R218P HSA and identifies two new Japanese R218P FDH patients unrelated to those described previously.Methods and Results: Recombinant R218H, R218P, and wild-type HSA were synthesized in yeast, and the affinities of these HSA species for l- and d-thyroxine were determined using fluorescence spectroscopy. The dissociation constants for the binding of wild-type, R218P, and R218H HSA to l-thyroxine were 1.44 × 10−6, 2.64 × 10−7, and 2.49 × 10−7 mol/L, respectively. The circular dichroism spectra of thyroxine bound to R218H and R218P HSA were markedly different, indicating that the structure of the thyroxine/HSA complex is different for either protein.Conclusions: The Kd values for l-thyroxine bound to R218P and R218H HSA determined in this study were similar. The extremely high serum total-thyroxine concentrations reported previously for R218P FDH patients (10-fold higher than those reported for R218H FDH patients) are not consistent with the Kd values determined in this study. Possible explanations for these discrepancies are discussed.
Type 1 Diabetes
Authors: Lernmark Åke 
Published: January 2020

AbstractType 1 (insulin-dependent) diabetes occurs worldwide and can appear at any age. The genetic susceptibility is strongly associated with HLA-DQ and DR on chromosome 6, but genetic factors on other chromosomes such as the insulin gene on chromosome 11 and the cytotoxic T-lymphocyte antigen gene on chromosome 2 may modulate disease risk. Numerous studies further support the view that environmental factors are important. Gestational infections may contribute to initiation, whereas later infections may accelerate islet β-cell autoimmunity. The pathogenesis is strongly related to autoimmunity against the islet β cells. Markers of autoimmunity include autoantibodies against glutamic acid decarboxylase, insulin, and islet cell antigen-2, a tyrosine phosphatase-like protein. Molecular techniques are used to establish reproducible and precise autoantibody assays, which have been subject to worldwide standardization. The diagnostic sensitivity (40–80%) and specificity (99%) of all three autoantibodies for type 1 diabetes are high, and double or triple positivity among first-degree relatives predicts disease. Combined genetic and antibody testing improved prediction in the general population despite the transient nature of these autoantibodies. Classification of diabetes has also been improved by autoantibody testing and may be used in type 2 diabetes to predict secondary failure and insulin requirement. Islet autoantibodies do not seem to be related to late complications but rather to metabolic control, perhaps because the presence of islet cell autoantibodies marks different residual β-cell function. Combined genetic and autoantibody screening permit rational approaches to identify subjects for secondary and tertiary intervention trials.
Microheterogeneity of Serum Glycoproteins in Patients with Chronic Alcohol Abuse Compared with Carbohydrate-deficient Glycoprotein Syndrome Type I
Authors: Henry Hugues , Froehlich Florian , Perret Renaud , Tissot Jean-Daniel , Eilers-Messerli Barbara , Lavanchy Daniel , Dionisi-Vici Carlo , Gonvers Jean-Jacques , Bachmann Claude 
Published: January 2020

AbstractBackground: Chronic alcohol abuse alters the normal N-glycosylation of transferrin, producing the carbohydrate-deficient transferrin isoforms. This alteration could be similar to that present in patients with carbohydrate-deficient glycoprotein syndrome type 1 (CDG1). We thus compared the alterations of N-glycans present in patients with alcoholism and patients with CDG1.Methods: The N-glycans of serum glycoproteins were compared in sera of patients with alcoholism, patients with CDG1, and controls by two-dimensional electrophoresis, neuraminidase, peptide:N-glycosidase F, and endoglycosidase F2 treatments. A specific antibody directed against the amino acid sequence surrounding the N-432 N-glycosylation site of transferrin was prepared (SZ-350 antibody).Results: In patients with alcoholism, the abnormal transferrin and α1-antitrypsin isoforms were devoid of a variable number of entire N-glycan moieties and were identical with those present in CDG1. In the serum of patients with alcoholism, this finding was less pronounced than in CDG1. In contrast to CDG1, there was no decrease in clusterin or serum amyloid P in patients with alcoholism. The SZ-350 antibody recognized only transferrin isoforms with one or no N-glycan moieties.Conclusion: Antibodies directed against specific N-glycosylation sites of glycoproteins could be useful for developing more specific immunochemical tests for the diagnosis of chronic alcohol abuse.
Standardization of Creatine Kinase-MB (CK-MB) Mass Assays: The Use of Recombinant CK-MB as a Reference Material
Authors: Christenson Robert H , Vaidya Hemant , Landt Yvonne , Bauer Roger S , Green Sol F , Apple Fred A , Jacob Ann , Magneson Gerald R , Nag Sumitra , Wu Alan HB , Azzazy Hassan ME 
Published: January 2020

AbstractBackground: The AACC assembled a committee to identify and validate a standard creatine kinase MB isoenzyme (CK-MB) material to improve the comparability of CK-MB mass assays.Methods: Three protocols were used. In protocol I, various CK-MB materials prepared in different matrices were screened as candidate standards. In protocol II, participating manufacturers calibrated their systems with concentrates of human heart CK-MB and then tested 20 patient samples to evaluate calibration bias. In protocol III, participating manufacturers calibrated their immunoassay systems using recombinant CK-MB2 (rCK-MB2) diluted into their respective sample diluents and measured 50 samples.Results: Candidate materials showed high recovery in stripped human serum, but bias improved only from 59% to 38%. These data led to the use of human heart CK-MB diluted in each manufacturer’s sample diluent. This strategy reduced bias from 31% to 15%. Because human heart CK-MB is difficult to provide, a lyophilized source of CK-MB2 was identified. rCK-MB2 was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, reversed-phase HPLC, intrinsic protein fluorescence, circular dichroism, agarose gel electrophoresis, immunoreactivity studies, high and low temperature stability, and reconstituted stability to be equivalent to human heart CK-MB. Calibration of immunoassay systems with rCK-MB2 added into each respective manufacturer’s sample diluent showed a 13% between-manufacturer bias.Conclusion: Lyophilized rCK-MB2 was determined suitable for use as a reference material for CK-MB mass assays.
Method for the Determination of Total Homocysteine in Plasma and Urine by Stable Isotope Dilution and Electrospray Tandem Mass Spectrometry
Authors: Magera Mark J , Lacey Jean M , Casetta Bruno , Rinaldo Piero 
Published: January 2020

Abstract
Background: Total homocysteine (tHcy) has emerged as an important independent risk factor for cardiovascular disease. Analytical methods are needed to accommodate the high testing volumes for tHcy and provide rapid turnaround.
Methods: We developed liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) method based on the analysis of 100 μL of either plasma or urine with homocystine-d8 (2 nmol) added as internal standard. After sample reduction and deproteinization, the analysis was performed in the multiple reaction monitoring mode in which tHcy and Hcy-d4 were detected through the transition from the precursor to the product ion (m/z 136 to m/z 90 and m/z 140 to m/z 94, respectively). The retention time of tHcy and Hcy-d4 was 1.5 min in a 2.5-min analysis.
Results: Daily calibrations between 2.5 and 60 μmol/L exhibited consistent linearity and reproducibility. At a plasma concentration of 0.8 μmol/L, the signal-to-noise ratio for tHcy was 17:1. The regression equation for the comparison between our previous HPLC method (y) and the LC-MS/MS method (x) was y = 1.097x − 1.377 (r = 0.975; Sy|x =1.595 μmol/L; n = 367), and for comparison between a fluorescence polarization immunoassay (Abbott IMx; y) and LC-MS/MS (x) was y = 1.039x + 0.025 (r = 0.969; Sy|x =1.146 μmol/L; n = 367). Inter- and intraassay CVs were 2.9–5.9% and 3.6–5.3%, respectively, at mean concentrations of 3.9, 22.7, and 52.8 μmol/L. Mean recovery of tHcy was 94.2% (20 μmol/L) and 97.8% (50 μmol/L).
Conclusions: The sensitivity and specificity of tandem mass spectrometry are well suited to perform high-volume analysis of tHcy. Reagents are inexpensive and sample preparation of a batch of 40 specimens is completed in less than 1 h and is amenable to automation.
Evaluation of a Particle-enhanced Turbidimetric Immunoassay for the Measurement of Immunoglobulin E in an ILab 900 Analyzer
Authors: Guaita Sandra , Simó Josep MA , Ferré Natàlia , Joven Jorge , Camps Jordi 
Published: January 2020

Abstract
Background: The measurement of immunoglobulin E (IgE) in serum is widely used in the diagnosis of allergic reactions and parasitic infections. We describe here a fully automated assay for human IgE suitable for routine application in a general chemistry analyzer.
Methods: We used an ILab 900® analyzer. This instrument automates a particle-enhanced immunoturbidimetric assay with an analysis time of 9 min.
Results: The assay was linear in the range 4–1000 kIU/L (r = 0.9998). The intra- and interassay CVs at 57, 235, and 434 kIU/L were &lt;3.5% and &lt;7.4%, respectively. The detection limit was 4 kIU/L. Hemoglobin (≤16 g/L), bilirubin (≤250 μmol/L), and myeloma paraproteins did not interfere with the assay. The assay showed good correlation with a microparticle enzyme immunoassay (r = 0.998) with a mean difference between methods of −6 ± 26 kIU/L.
Conclusion: The new automated serum assay for IgE is an attractive alternative that avoids the need for dedicated instrumentation.
Evaluation of Measurement Sites for Noninvasive Blood Glucose Sensing with Near-Infrared Transmission Spectroscopy
Authors: Burmeister Jason J , Arnold Mark A 
Published: January 2020

AbstractSix putative measurement sites were evaluated for noninvasive sensing of blood glucose by first-overtone near-infrared spectroscopy. The cheek, lower lip, upper lip, nasal septum, tongue, and webbing tissue between the thumb and forefinger were examined. These sites were evaluated on the basis of their chemical and physical properties as they pertain to the noninvasive measurement of glucose. Critical features included the effective optical pathlength of aqueous material within the tissue and the percentage of body fat within the optical path. Aqueous optical paths of 5 mm are required to measure clinically relevant concentrations of glucose in the first-overtone region. All of the tested sites met this requirement. The percentage of body fat affects the signal-to-noise ratio of the measurement and must be minimized for reliable glucose sensing. The webbing tissue contains a considerable amount of fat tissue and is clearly the worse measurement site. All other sites possess substantially less fat, with the least amount of fat in tongue tissue. For this reason, the tongue provides spectra with the highest signal-to-noise ratio and is, therefore, the site of choice on the basis of spectral quality.
Thin Film Biosensor for Rapid Visual Detection of Nucleic Acid Targets
Authors: Ostroff Rachel M , Hopkins Deborah , Haeberli Ayla B , Baouchi Wahab , Polisky Barry 
Published: January 2020

Abstract
Background: We have developed a silicon-based biosensor that generates a visual signal in response to nucleic acid targets.
Methods: In this system, capture oligonucleotide probes are immobilized on the surface of the biosensor. Interaction of the capture probes with a complementary target and a biotinylated detector oligonucleotide allows initiation of formation of an organic thin film on the biosensor. Thin film formation is completed by enzymatic activity of peroxidase conjugated to an anti-biotin antibody. Peroxidase catalyzes deposition of an insoluble product onto the silicon surface, generating a uniform thin film. The increased thickness on the surface alters the perceived color of the biosensor through changes in the interference patterns of reflected light from the surface, causing a color change from gold to purple.
Results: The biosensor results may be evaluated by direct visual inspection or quantified by ellipsometry. Results are obtained in 25 min with a detection limit of 5 pmol/L (150 amol/sample). Selectivity of the biosensor is demonstrated by discrimination of single nucleotide mismatches. Multitarget arrays are also analyzed with the thin film biosensor, and the system is capable of detecting targets from human serum and urine.
Conclusions: The biosensor surface is inexpensive to produce, and the assay format is simple and rapid. The thin film biosensor is adaptable to a wide variety of nucleic acid detection applications, including rapid diagnostic testing for infectious disease panels, antibiotic resistance panels, or allelic discrimination of specific genetic markers.
Molecular Forms of Prostate-specific Antigen in Malignant and Benign Prostatic Tissue: Biochemical and Diagnostic Implications
Authors: Jung Klaus , Brux Brigitte , Lein Michael , Rudolph Birgit , Kristiansen Glen , Hauptmann Steffen , Schnorr Dietmar , Loening Stefan A , Sinha Pranav 
Published: January 2020

AbstractBackground: Patients with prostate cancer (PCa) show a lower ratio of free prostate-specific antigen (fPSA) to total PSA (tPSA) in serum than patients with benign prostatic hyperplasia (BPH). The patterns of the intracellular PSA isoforms in malignant and benign prostatic tissue have been studied as potential molecular reasons for this phenomenon.Methods: Prostatic tissue samples were obtained after cystoprostatectomy from patients with bladder cancer (n = 10), from BPH patients (transurethral resection of the prostate, n = 10; adenomectomy, n = 10), and from the cancerous and noncancerous parts of the same prostates removed surgically by prostatectomy because of PCa (n = 20). PSA pattern was characterized by gel filtration, immunoblotting, and immunoassays for tPSA, fPSA, α1-antichymotrypsin-PSA (ACT-PSA), and complexed PSA (Bayer Immuno 1 assay). Comparisons were made with the PSA concentrations in serum.Results: The major portion of tPSA in all tissue samples was fPSA; complexed PSA forms were &lt;2%. Samples from cystoprostatectomy patients had the lowest and those from adenomectomy patients the highest values of tPSA and fPSA. PSA concentrations were lower in cancerous than in the noncancerous parts of the prostate. No significant correlations were found between tumor stage or grade and the amounts of tPSA, fPSA, and ACT-PSA in tissue. Tissue PSA values were not correlated with the serum PSA concentrations nor with the ratios fPSA/tPSA and ACT-PSA/tPSA in sera.Conclusions: The amounts of tPSA and the PSA isoforms in prostatic tissue explain neither the concentrations of tPSA and PSA isoforms in serum nor the behavior of the ratio fPSA/tPSA in patients with BPH and PCa.
Ratio of Free or Complexed Prostate-specific Antigen (PSA) to Total PSA: Which Ratio Improves Differentiation between Benign Prostatic Hyperplasia and Prostate Cancer?
Authors: Jung Klaus , Elgeti Ulrike , Lein Michael , Brux Brigitte , Sinha Pranav , Rudolph Birgit , Hauptmann Steffen , Schnorr Dietmar , Loening Stefan A 
Published: January 2020

Abstract
Background: The aim of this study was to compare the diagnostic utility of a new assay that measures all forms of prostate-specific antigen complexed (cPSA) to serum proteins except α2-macroglobulin with the assay of free PSA (fPSA) and the corresponding ratios to total PSA (tPSA) to improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa).
Methods: Serum samples were collected from 91 men without prostate disease and with normal digital rectal examination (controls), 144 untreated patients with PCa, and 89 patients with BPH. tPSA and cPSA were measured using the Bayer Immuno 1 system; fPSA and the additional tPSA were measured with the Roche Elecsys system.
Results: The median cPSA/tPSA, fPSA/tPSA, and fPSA/cPSA ratios were significantly different between patients with BPH and PCa (78.7% vs 90.7%, 25.5% vs 12.1%, and 36.8% vs 14.3%, respectively; P &lt;0.001). No correlations of cPSA and its ratios to tumor stage and grade were found. ROC analysis showed that cPSA was not different from tPSA (areas under the curve, 0.632 vs 0.568), whereas the cPSA/tPSA ratio was similar to the fPSA/tPSA ratio in increasing discrimination between BPH and PCa patients with tPSA concentrations in the tPSA gray zone between 2 and 10 μg/L (areas under the curve, 0.851 vs 0.838).
Conclusions: Compared with tPSA, the fPSA/tPSA and cPSA/tPSA ratios both improve the differentiation between BPH and PCa comparably and are similarly effective in reducing the rate of unnecessary biopsies, whereas cPSA alone does not have any effect.
Assessment of Between-Instrument Variations in a HPLC Method for Serum Lipoproteins and Its Traceability to Reference Methods for Total Cholesterol and HDL-Cholesterol
Authors: Usui Shinichi , Nakamura Masakazu , Jitsukata Kazuhiro , Nara Masayuki , Hosaki Seijin , Okazaki Mitsuyo 
Published: January 2020

AbstractBackground: The main purpose of this study was to evaluate the between-instrument variation of the HPLC method for the measurement of total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), VLDL-cholesterol (VLDL-C), chylomicron cholesterol (CM-C), LDL size, and HDL size. Furthermore, the accuracy of the HPLC was assessed for the determination of TC and HDL-C, compared with CDC reference methods.Methods: We used four HPLC instruments with different column-load numbers from 250 to 5000. For accuracy assessment of TC and HDL-C, we used the reference methods recommended by the CDC.Results: The values measured by the four instruments were highly correlated with each other (mean r = 0.965), and the absolute mean differences were 4–43 mg/L for TC, 4–30 mg/L for HDL-C, 0–48 mg/L for LDL-C, 7–66 mg/L for VLDL-C, 0–7 mg/L for CM-C, 0.1–0.3 nm for LDL size, and 0–0.1 nm for HDL size. For TC, the HPLC instruments showed high correlation and good agreement with the reference method: r = 0.997; total error &lt;6.6%; absolute mean bias &lt;1.2%. For HDL-C, the results from the HPLC method were significantly higher (10.8% absolute mean bias) than those of the CDC reference method, in spite of good correlation between the two methods (r = 0.998).Conclusions: The between-instrument variation in serum lipoprotein analysis by HPLC was confirmed to be very small. This method met the US National Cholesterol Education Program’s performance criteria for TC but not for HDL-C.
Transferrin Polymorphism Influences Iron Status in Blacks
Authors: Kasvosve Ishmael , Delanghe Joris R , Gomo Zvenyika A R , Gangaidzo Innocent T , Khumalo Hlosukwazi , Wuyts Birgitte , Mvundura Elisha , Saungweme Thokozile , Moyo Victor M , Boelaert Johan R , Gordeuk Victor R 
Published: January 2020

Abstract
Background: Genetic variants of human transferrin (TF) have been described, but little is known about their functional differences. We studied iron status according to TF phenotype in a healthy Zimbabwean population and in subjects at risk of African iron overload.
Methods: The study population consisted of 483 nondrinkers, 31 drinking spouse pairs, and 5 family pedigrees (n = 88) with index cases of iron overload. TF phenotypes were determined using starch gel electrophoresis. To evaluate iron status, serum iron, total iron-binding capacity (TIBC), ferritin, and soluble TF receptors were measured, and the percentage of saturation and the serum iron:TF ratio were calculated. The binding of the TF variants was studied by equilibrium dialysis.
Results: The reference population was characterized by a high TF D allele frequency (0.050) and a complete absence of homozygous TF DD individuals. Similar allele frequencies were observed in subjects at risk of African iron overload. In the reference population, male TF CD heterozygotes had significantly lower (P &lt;0.01) values for serum iron, TIBC, TF saturation, and serum iron:TF ratio than the TF CC homozygotes; in females, only TIBC was significantly different. Overall red blood cell indices did not differ according to TF phenotype. In the population at risk of African iron overload, only serum iron:TF ratio was consistently significantly lower in TF CD phenotypes (P &lt;0.05). After equilibrium dialysis, the amount of iron bound by TF was significantly lower (P &lt;0.01) in TF CD individuals.
Conclusions: The present data demonstrate a functional difference between TF phenotypes in blacks.