bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proton nuclear magnetic resonance spectral profiles of urine in type II diabetic patients
Authors: Messana Irene , Forni Franca , Ferrari Franco , Rossi Cristina , Giardina Bruno , Zuppi Cecilia 
Published: January 2020

Abstract
Serial urine samples of 33 type II diabetic patients and 20 control subjects were examined by 1H nuclear magnetic resonance (NMR). Metabolites including lactate, citrate, glycine, alanine, hippurate, trimethylamine-N-oxide, and dimethylamine were identified in all subjects although in higher concentrations in diabetic patients. Other analytes, such as creatine, acetate, betaine, and ketone bodies, were found more frequently and in greater concentrations in diabetics than in controls. In addition, although lactate, citrate, alanine, and hippurate concentrations increased with increasing glycosuria and glycohemoglobin, trimethylamine-N-oxide and dimethylamine were present at high concentrations even in diabetics with good metabolic control. 1H NMR spectroscopy permitted us to explore the relationships among the metabolites present in the urine samples and to obtain information about the disease status in type II diabetic patients.
Differences of bone alkaline phosphatase isoforms in metastatic bone disease and discrepant effects of clodronate on different skeletal sites indicated by the location of pain
Authors: Magnusson Per , Larsson Lasse , Englund Gunnar , Larsson Brita , Strang Peter , Selin-Sjögren Lena 
Published: January 2020

AbstractWe compared clodronate with placebo administration in 42 primarily or secondarily hormone-refractory prostate cancer patients with skeletal metastases and persisting pain. Serum total alkaline phosphatase (ALP), bone ALP isoforms, osteocalcin, cross-linked carboxy-terminal telopeptide of type I collagen, and prostate-specific antigen were analyzed before and after 1 month of treatment. Six ALP isoforms were quantified by HPLC: one bone/intestinal, two bone (B1, B2), and three liver ALP isoforms. The most apparent difference compared with healthy males was observed for the bone ALP isoform B2. Patients and healthy males had a B2 activity corresponding to 75% and 35% of the total ALP activity, respectively (P &lt;0.0001). We propose that the different bone ALP isoforms reflect different stages of osteoblast differentiation during the extracellular matrix maturation phase of osteogenesis. All bone markers except osteocalcin increased after 1 month of clodronate administration. These increases were associated with pain only in the upper part of the body. We suggest that the uptake of clodronate by the skeleton was not uniform during our treatment period.
International Federation of Clinical Chemistry standardization project for the measurement of lipoprotein(a). Phase I. Evaluation of the analytical performance of lipoprotein(a) assay systems and commercial calibrators
Authors: Tate Jillian R , Rifai Nader , Berg Kåre , Couderc Rémy , Dati Francesco , Kostner Gert M , Sakurabayashi Ikunosuke , Steinmetz Armin 
Published: January 2020

AbstractA secondary reference material for lipoprotein(a) is required to standardize the measurement of lipoprotein(a) in clinical laboratories worldwide. Towards this aim, the International Federation of Clinical Chemistry Working Group for the Standardization of Lipoprotein(a) Assays has initiated a standardization project involving a total of 33 diagnostic company and clinical chemistry laboratories from 12 countries. In Phase 1, the analytical performance of 40 lipoprotein(a) assay systems was evaluated by testing sera and manufactured lipoprotein(a) calibrator materials for precision, linearity, and parallelism. Twenty test systems were nonoptimized according to the results for a pooled serum, which tested nonlinear in 16 systems and imprecise in 4. Acceptable analytical properties and harmonization of lipoprotein(a) values were shown by some commercial calibrators, suggesting their possible use as reference materials. This study highlights the problems that currently occur for lipoprotein(a) measurement in existing assay systems.
Early detection of peritonitis in continuous ambulatory peritoneal dialysis patients by use of chemiluminescence: evaluation of diagnostic accuracy by receiver-operating characteristic curve analysis
Authors: Dalaman Gönül , Haklar Goncagül , Sipahiu Armand , Özener Çetin , Akoĝlu Emel , Yalçin A Süha 
Published: January 2020

AbstractContinuous ambulatory peritoneal dialysis (CAPD) is now a widely accepted treatment for end-stage renal disease. However, the high incidence of peritonitis is a major complication of CAPD. Polymorphonuclear leukocytes (PMNs) play a major role in antimicrobial response of the host. During phagocytosis, the PMNs undergo a striking increase in oxidative metabolism, known as the respiratory burst, and emit light as chemiluminescence (CL). CL is thus a sensitive measure of PMN oxidative potential and correlates well with antimicrobial activity. In view of the observation of increased susceptibility to infection in CAPD patients, we have studied lucigenin- and luminol-enhanced CL in peritoneal fluids of these patients and assessed the diagnostic accuracy of these tests by ROC curve analysis. ROC curves showed diagnostic accuracies for both tests that were superior to counts of PMNs in the dialysis fluid (P &lt;0.001). At selected cutoff values of 150 000 cpm/vial for lucigenin CL and 600 000 cpm/vial for luminol CL, sensitivities were 100%. Specificities for lucigenin and luminol CL were 89% and 80%, respectively. Our results suggest that CL measurements can be used as an early marker for the presence of infection in CAPD patients.
Inhibition of LDL oxidation by melatonin requires supraphysiologic concentrations
Authors: Duell P Barton , Wheaton David L , Shultz Amy , Nguyen Hien 
Published: January 2020

AbstractMelatonin has been suggested as a potent antioxidant that may protect against development of atherosclerosis and cancer; however, these effects are unproven and controversial. The antioxidant capacity of melatonin was tested in comparison with α-tocopherol, ascorbic acid, and the melatonin precursors tryptophan and serotonin, by measuring inhibition of metal ion-mediated and human macrophage-mediated oxidation of LDL. Melatonin had weak antioxidant activity that was detectable only at concentrations 10 000- to 100 000-fold higher than physiologic concentrations. These results were comparable with published data showing that the radical scavenging activity of melatonin requires markedly supraphysiologic concentrations. In contrast, α-tocopherol was 50- to 100-fold more potent and was efficacious at physiologic concentrations. Ascorbic acid and tryptophan also were active at physiologic concentrations and were significantly more potent than melatonin. In summary, extremely supraphysiologic concentrations of melatonin had only weak antioxidant activity, which was surpassed by α-tocopherol, ascorbic acid, and tryptophan.
What is hemoglobin A1c? An analysis of glycated hemoglobins by electrospray ionization mass spectrometry
Authors: Peterson Karen P , Pavlovich James G , Goldstein David , Little Randie , England Jack , Peterson Charles M 
Published: January 2020

AbstractHemoglobin A1c (HbA1c) is a stable minor Hb variant formed in vivo by posttranslational modification by glucose, originally identified by using cation exchange chromatography, and containing primarily glycated N-terminal β-chains. However, the structure(s) of the quantified species has not been elucidated, and the available methods lack a reference standard. We used electrospray ionization mass spectrometry to determine the extent of glycation of samples separated by boronate affinity and/or cation exchange chromatography. Analyses of clinical samples were consistent with the curvilinear relationship of patient glucose and HbA1c. As glycation increased, the ratio of β-chain to α-chain glycation increased, and the number of glycation sites on the β-chain increased, although these were relatively minor components. We found several glycated species that cochromatographed with HbA1c on cation exchange, including species with both glycated α- and β-chains, nonglycated α- and glycated β-chains, and multiply glycated β-chains. The combined use of affinity and cation exchange chromatography with structural confirmation by electrospray ionization mass spectrometry was found to be useful in producing samples of sufficient purity for the standardization of glycohemoglobin clinical assays.
Identification of MEN1 Mutations in Sporadic Enteropancreatic Neuroendocrine Tumors by Analysis of Paraffin-embedded Tissue
Authors: Mailman Matthew D , Muscarella Peter , Schirmer William J , Ellison E Christopher , O’Dorisio Thomas M , Prior Thomas W 
Published: January 2020

Abstract
Gastrinomas and other gastrointestinal neuroendocrine tumors may occur sporadically or as part of the inherited syndrome multiple endocrine neoplasia type 1 (MEN1). Mutations in the recently identified MEN1 gene have been described in sporadic gastrinomas and insulinomas. This study describes techniques used to identify mutations in the MEN1 gene in DNA extracted from paraffin-preserved tissue. Two novel mutations are identified in the MEN1 gene from nine archived paraffin-embedded neuroendocrine tumors, demonstrating that retrospective genetic analysis can be used to identify mutations in the MEN1 gene from preserved tissue. Conditions are provided by which paraffin-embedded tissue can be used as a source of genetic material for sequence information of sufficient quality for mutational studies of the MEN1 gene. It should also be possible to apply this retrospective genetic analysis of paraffin-embedded tissue to other disease models.
Validation of Double Gradient Denaturing Gradient Gel Electrophoresis through Multigenic Retrospective Analysis
Authors: Cremonesi Laura , Carrera Paola , Fumagalli Antonella , Lucchiari Sabrina , Cardillo Elena , Ferrari Maurizio , Righetti Sabina Carla , Zunino Franco , Righetti Pier Giorgio , Gelfi Cecilia 
Published: January 2020

Abstract
Among established techniques for the identification of either known or new mutations, denaturing gradient gel electrophoresis (DGGE) is one of the most effective. However, conventional DGGE is affected by major drawbacks that limit its routine application: the different denaturant gradient ranges and migration times required for different DNA fragments. We developed a modified version of DGGE for high-throughput mutational analysis, double gradient DGGE (DG-DGGE), by superimposing a porous gradient over the denaturant gradient, which maintains the zone-sharpening effect even during lengthy analyses. Because of this innovation, DG-DGGE achieves the double goals of retaining full effectiveness in the detection of mutations while allowing identical run time conditions for all fragments analyzed. Here we use retrospective analysis of a large number of well-characterized mutations and polymorphisms, spanning all predicted melting domains and the whole genomic sequence of three different genes—the cystic fibrosis transmembrane conductance regulator (CFTR), the β-globin, and the p53 genes—to demonstrate that DG-DGGE may be applied to the rapid scanning of any sequence variation.
A New Gas Chromatography–Mass Spectrometry Method for Simultaneous Determination of Total and Free trans-3′-Hydroxycotinine and Cotinine in the Urine of Subjects Receiving Transdermal Nicotine
Authors: Ji Allena J , Lawson George M , Anderson Rodger , Dale Lowell C , Croghan Ivana T , Hurt Richard D 
Published: January 2020

Abstracttrans-3′-Hydroxycotinine (THOC) has been recognized as the most abundant metabolite of nicotine. In an attempt to assess THOC and cotinine (COT) concentrations during nicotine transdermal therapy, we developed a new quantitative gas chromatography–mass spectrometry (GC–MS) method for simultaneous determination of total and free THOC and COT in human urine. The method utilizes the following: (a) hydrolysis of conjugated THOC and COT by β-glucuronidase; (b) basic extraction of THOC and COT with mixed dichloromethane and n-butyl acetate; (c) derivatization of THOC with bis(trimethylflurosilyl)acetamide; and (d) separation and identification by GC–MS with selective ion monitoring. Lower limits of quantification for the assay were 50 and 20 μg/L for THOC and COT, respectively. The intra- and interassay CVs were 4.4% and 11% for THOC, and 3.9% and 10% for COT at 1000 μg/L. The results from six consecutive 24-h urine collections in 71 subjects administered daily transdermal nicotine doses of 11, 22, and 44 mg showed that, on average, free THOC was 76% of total THOC and free COT was 48% of total COT in all subjects. THOC is the major metabolite of nicotine and constitutes 20% of total nicotine intake at steady state, whereas urinary nicotine and COT excretion were 8% and 17%, respectively. The method is useful for simultaneous determination of free and total THOCand COT and can be used to assess the urinary excretion of these metabolites during transdermal nicotine therapy.
Significance of l-Alloisoleucine in Plasma for Diagnosis of Maple Syrup Urine Disease
Authors: Schadewaldt Peter , Bodner-Leidecker Annette , Hammen Hans-Werner , Wendel Udo 
Published: January 2020

AbstractBackground: The significance of plasma l-alloisoleucine, which is derived from l-isoleucine in vivo, for diagnosis of maple syrup urine disease (MSUD) was examined.Methods: Branched-chain l-amino acids were measured by automatic amino acid analysis.Results: Alloisoleucine reference values in plasma were established in healthy adults [1.9 ± 0.6 μmol/L (mean ± SD); n = 35], children 3–11 years (1.6 ± 0.4 μmol/L; n = 17), and infants &lt;3 years (1.3 ± 0.5 μmol/L; n = 37). The effect of dietary isoleucine was assessed in oral loading tests. In controls receiving 38 μmol (n = 6; low dose) and 1527 μmol (n = 3; high dose) of l-isoleucine per kilogram of body weight, peak increases of plasma isoleucine were 78 ± 24 and 1763 ± 133 μmol/L, respectively; the peak increase of alloisoleucine, however, was negligible for low-dose (&lt;0.3 μmol/L) and minor for high-dose (5.5 ± 2.1 μmol/L) load. In patients with diabetes mellitus, ketotic hypoglycemia, phenylketonuria, and obligate heterozygous parents of MSUD patients, alloisoleucine was not significantly different from healthy subjects. Therefore, a plasma concentration of 5 μmol/L was used as a cutoff value. In patients with classical MSUD (n = 7), alloisoleucine was beyond the cutoff value in 2451 of 2453 unselected samples. In patients with variant MSUD (n = 9), alloisoleucine was &gt;5 μmol/L in all samples taken for establishment of diagnosis and in 94% of the samples taken for treatment control (n = 624). With the other branched-chain amino acids, the frequency of diagnostically significant increases was &lt;45%.Conclusions: The present findings indicate that plasma l-alloisoleucine above the cutoff value of 5 μmol/L is the most specific and most sensitive diagnostic marker for all forms of MSUD.
Increased Fetal DNA Concentrations in the Plasma of Pregnant Women Carrying Fetuses with Trisomy 21
Authors: Lo YM Dennis , Lau Tze K , Zhang Jun , Leung Tse N , Chang Allan MZ , Hjelm N Magnus , Elmes R Sarah , Bianchi Diana W 
Published: January 2020

AbstractBackground: The recent discovery of the presence of circulating cell-free fetal DNA in maternal plasma opens up new prenatal diagnostic applications and provides new avenues for clinical investigation. It is of research and potential diagnostic interest to determine whether fetal trisomy 21 may be associated with quantitative abnormalities of circulating fetal DNA in maternal plasma.Methods: Maternal plasma samples were prospectively collected from two centers situated in Hong Kong and Boston. Samples collected from Boston consisted of 7 women carrying male trisomy 21 fetuses, 19 carrying euploid male fetuses, and 13 carrying female fetuses. Samples collected from Hong Kong consisted of 6 women carrying male trisomy 21 fetuses, 18 carrying euploid male fetuses, and 10 carrying female fetuses. Male fetal DNA in maternal plasma was measured using real-time quantitative Y-chromosomal PCR.Results: For patients recruited from Boston, the median circulating fetal DNA concentrations in women carrying trisomy 21 and euploid male fetuses were 46.0 genome-equivalents/mL and 23.3 genome-equivalents/mL, respectively (P = 0.028). For patients recruited from Hong Kong, the median circulating fetal DNA concentrations in women carrying trisomy 21 and euploid male fetuses were 48.2 genome-equivalents/mL and 16.3 genome-equivalents/mL, respectively (P = 0.026). None of the samples from women carrying female fetuses had detectable Y-chromosomal signals.Conclusions: Abnormally high concentrations of circulating fetal DNA are found in a proportion of women carrying fetuses with trisomy 21. The robustness and reproducibility of real-time PCR analysis of maternal plasma makes it a valuable tool for cross-institutional collaboration involving centers located in different parts of the world.
Common Diagnostic Test Panels for Clinical Evaluation of New Primary Care Outpatients in Japan: A Cost-Effectiveness Evaluation
Authors: Takemura Yuzuru , Ishida Haku , Inoue Yuji , Beck J Robert 
Published: January 2020

Abstract
Background: The Japan Society of Clinical Pathology (JSCP) has developed a guideline for common diagnostic test utilization in new primary care outpatients. To determine the scientific and economic validity of the JSCP panel testing system, we analyzed cost-effectiveness parameters of test panels advocated.
Methods: The “Essential Laboratory Tests” panel (2) [ELT(2) panel], a package of common diagnostic tests added to the ELT(1) baseline health-status screening panel, was applied to 540 new outpatients who visited the Comprehensive Medicine Clinics in an academic medical center during 1991 to 1997. A “useful result” (UR) of testing was defined as a finding that contributed to a change in a physician’s diagnosis- or decision-making, relating to a “tentative initial diagnosis” (TID) obtained from history and physical examination alone.
Results: Clinical usefulness was demonstrated in 259 patients with ELT(2), in whom 398 URs were generated. Clinical effectiveness (UR/TID) ranged from 1.65 (hematological) to 0.088 (neurological disease), with a cost disparity from ¥1251 (∼$10) to ¥23 037 (∼$200) per UR. A total of 1137 tests generated URs. We further assessed the clinical effectiveness and economic efficiency (cost/UR) of ELT(1) and restructured panels. Use of the ELT(1) alone generated 244 URs in 167 patients. The poor efficiency of the ELT(1) panel was markedly improved with the addition of certain ELT(2)-specific tests in liver/pancreatobiliary, metabolic/endocrine, and cardiovascular disease groups.
Conclusions: A wide disparity in the utility of ELT panels in different patient groups does not support the JSCP recommendation of their routine use for new outpatients. Selective test combinations should be used in selected patient groups.
Dried Plasma Spot Measurements of Ferritin and Transferrin Receptor for Assessing Iron Status
Authors: Flowers Carol H , Cook James D 
Published: January 2020

AbstractBackground: Efforts to reduce the high global prevalence of nutritional anemia require the use of both reliable laboratory assays to distinguish iron deficiency from other causes of anemia and cost-effective methods for collection of blood specimens under field conditions. The suitability of using small plasma samples spotted and dried on filter paper for measurements of plasma ferritin and transferrin receptor was evaluated in the present study.Methods: Blood specimens obtained from 73 male and 83 female subjects (19–40 years) representing a wide range of iron status were used to perform parallel measurements of plasma ferritin and transferrin receptor on whole plasma and spotted plasma samples.Results: Ratio plots, evaluating the acceptability and precision of the spot method in ferritin and transferrin receptor assays, showed the expected proportion of data points within the 95% prediction interval. In the composite group of 156 subjects, both the whole plasma and plasma spot methods gave a geometric mean transferrin receptor/ferritin ratio of 18. The regression equation for the ratio was logy = 1.045 logx − 0.05126; r = 0.986; P &lt;0.0001. The ratio of transferrin receptor/ferritin determined from plasma spots correctly identified all 12 subjects with iron deficiency anemia compared with 11 of the 12 for whole plasma measurements.Conclusions: Measurements of ferritin and transferrin receptor on plasma spotted and dried on filter paper are comparable to whole plasma values for the identification of iron deficiency anemia. The use of dried plasma spots will facilitate the collection, storage, and transport of samples in epidemiological studies of anemia prevalence.
Inflammatory Markers in Men with Angiographically Documented Coronary Heart Disease
Authors: Rifai Nader , Joubran Rana , Yu Harry , Asmi Mohamad , Jouma Mohidien 
Published: January 2020

Abstract
Background: Recent evidence suggests that atherosclerosis is a chronic inflammatory process. In this study, we examined several markers of inflammation in men with coronary heart disease (CHD) and appropriate controls.
Methods: The concentrations of C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6), and soluble intracellular adhesion molecule (sICAM-1) were examined in 100 men with angiographically documented CHD and 100 age-, gender-, and smoking-matched controls with no history of CHD. We assessed the association of these markers with severity of disease as indicated by &gt;50% obstruction in one vessel (n = 30), two vessels (n = 39), or three vessels (n = 31).
Results: Significant increases were noted in serum CRP (median for cases vs controls, 3.4 vs 1.5 mg/L; P &lt;0.0001), SAA (5.9 vs 3.7 mg/L; P &lt;0.005), and IL-6 (2.3 vs 1.7 ng/L; P &lt;0.013) in patients with CHD compared with controls. These differences remained significant after correction for age, smoking, hypertension, diabetes, and lipid and homocysteine concentrations. Plasma sICAM-1 was not significantly different between the two groups (335 vs 339 μg/L). No significant correlation was seen between these markers and the severity of coronary disease.
Conclusions: Concentrations of CRP, SAA, and IL-6 were increased in patients with CHD but failed to correlate with severity of coronary disease. These markers might reflect the diffuse atherosclerotic process in the vascular system rather than the degree of localized obstruction from coronary lesions.