bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between the Prevalence of Antibodies to β2-Glycoprotein I, Prothrombin, Protein C, Protein S, and Annexin V in Patients with Systemic Lupus Erythematosus and Thrombotic and Thrombocytopenic Complications
Authors: Nojima Junzo , Kuratsune Hirohiko , Suehisa Etsuji , Futsukaichi Yoshiaki , Yamanishi Hachiro , Machii Takashi , Iwatani Yoshinori , Kanakura Yuzuru 
Published: January 2020

AbstractBackground: Anti-phospholipid (aPL) antibodies (Abs) frequently found in the plasma of patients with systemic lupus erythematosus (SLE) have been associated with thrombotic complications. Our aim was to clarify the roles in thrombosis of aPL Abs that react with complexes of phospholipids and plasma proteins such as β2-glycoprotein I (β2-GPI), prothrombin, protein C, protein S, and annexin V.Methods: We determined the prevalence of aPL Abs to various phospholipid-binding plasma proteins in SLE patients with arterial thrombosis (30 cases), venous thrombosis (19 cases), thrombocytopenia (14 cases), fetal loss (14 cases), and patients without complications (91 cases). The aPL Abs were measured by an ELISA system in which human plasma proteins (β2-GPI, prothrombin, protein C, protein S, and annexin V) were immobilized on γ-irradiated or plain polystyrene plates.Results: All types of aPL Abs were frequently observed in the patients with SLE when γ-irradiated polystyrene plates were used (51 of 168 cases positive for anti-β2-GPI, 94 of 168 cases positive for anti-prothrombin, 36 of 168 cases positive for anti-protein C, 47 of 168 cases positive for anti-protein S, and 50 of 168 cases positive for anti-annexin V), whereas no Abs to these plasma proteins were detected when plain polystyrene plates were used. Multivariate analysis confirmed that both anti-β2-GPI and anti-prothrombin Abs were significant risk factors for arterial thrombosis [odds ratios (ORs), 8.8 and 14.5, respectively; 95% confidence intervals (CIs), 3.2–25 and 1.8–116, respectively] but not for venous thrombosis. The presence of anti-protein S Abs was a significant risk factor for venous thrombosis (OR, 30.4; CI, 3.3–281) but not for arterial thrombosis. The only significant risk factor for fetal loss was the presence of anti-annexin V Abs (OR, 5.9; CI, 1.4–14.8).Conclusions: Patients with SLE frequently have some aPL Abs to β2-GPI, prothrombin, protein C, protein S, and annexin V. Thrombotic complications in SLE may depend on the antigenic specificities of these Abs, alone or in combination.
Serial Measurements of C-Reactive Protein and Interleukin-6 in the Immediate Postnatal Period: Reference Intervals and Analysis of Maternal and Perinatal Confounders
Authors: Chiesa Claudio , Signore Fabrizio , Assumma Marcello , Buffone Elsa , Tramontozzi Paola , Osborn John F , Pacifico Lucia 
Published: January 2020

Abstract
Background: There is a wide range of reported sensitivities and specificities for C-reactive protein (CRP) and interleukin-6 (IL-6) in the detection of early-onset neonatal infection. This prompted us to assess reference intervals for CRP and IL-6 during the 48-h period immediately after birth and to identify maternal and perinatal factors that may affect them.
Methods: CRP and IL-6 values were prospectively obtained for 148 healthy babies (113 term, 35 near-term) at birth and at 24 and 48 h of life, and from their mothers at delivery.
Results: Upper reference limits for CRP at each neonatal age were established. At birth, CRP was significantly lower than at 24 and 48 h of life. Rupture of membranes ≥18 h, perinatal distress, and gestational hypertension significantly affected the neonatal CRP dynamics, but at specific ages. There was no correlation between CRP concentrations in mothers and their offspring at birth. The IL-6 values observed in the delivering mothers and in their babies at all three neonatal ages were negatively associated with gestational age. In the immediate postnatal period, IL-6 dynamics for term babies were significantly different from those for near-term babies. Maternal IL-6 concentrations correlated with babies’ IL-6 concentrations only for term deliveries. Apgar score had a significant effect on babies’ IL-6 values at birth.
Conclusions: The patterns of CRP and IL-6 responses in the healthy neonate should be taken into account to optimize their use in the diagnosis of early-onset neonatal sepsis.
Novel Approach for the Determination of the Redox Status of Homocysteine and Other Aminothiols in Plasma from Healthy Subjects and Patients with Ischemic Stroke
Authors: Williams Robert H , Maggiore Jack A , Reynolds Robert D , Helgason Cathy M 
Published: January 2020

AbstractBackground: Plasma “redox” status can be assessed by measurements of reduced (r)-, free (f)-, oxidized (ox)-, and protein-bound (b)-homocysteine (Hcy) plus the related aminothiols cysteine, cysteinylglycine (CysGly), and glutathione (GSH), but sample collection has been complex. The redox status has not been determined in ischemic stroke patients and may provide increased understanding of its role in pathogenesis. We wished to examine the feasibility of this measurement in samples collected in readily available acidic sodium citrate.Methods: We measured aminothiols and their stability in stabilized protein-free filtrate using acidic sodium citrate (BioPool® StabilyteTM, pH 4.3) vs EDTA whole blood. Before analysis, plasma samples were also ultrafiltered to obtain a protein-free filtrate. The concentrations of total Hcy (tHcy), fHcy, and rHcy and their related aminothiols, cysteine, cysteinylglycine, and glutathione were simultaneously determined on acidic sodium-citrated blood using reversed-phase HPLC with fluorescence detection. Bound and oxidized aminothiols were calculated by difference using the concentrations of the total, free, and reduced fractions. Using this approach, we compared the redox status in newly diagnosed ischemic stroke patients (n = 20) and healthy age- and sex-matched subjects (n = 20).Results: tHcy, tCys, tCysGly, and tGSH concentrations in whole blood with Stabilyte were stable for 8 h; the reduced fraction of each aminothiol was stable for 4 h. Recovery in the protein-free filtrate was 90–100% for all reduced thiols in acidified sodium-citrated blood. Patients with ischemic stroke had higher plasma tHcy, fHcy, bHcy, rHcy, and oxHcy (P &lt;0.0005) and higher plasma t-, f-, r-, and oxCys (P &lt;0.05). t-, b-, and rCysGly concentrations were lower in the stroke patients (P &lt;0.05), as were t-, b-, and oxGSH (P &lt;0.005).Conclusions: Collection of blood in acidic sodium citrate (BioPool Stabilyte) permits the determination of the redox status of Hcy and its related aminothiols, which may add to the understanding of their relationship to the etiology of cerebrovascular disease.
Quantification of Unconjugated Metanephrines in Human Plasma without Interference by Acetaminophen
Authors: Roden Michael , Raffesberg Wolfgang , Raber Wolfgang , Bernroider Elisabeth , Niederle Bruno , Waldhäusl Werner , Gasic Slobodan 
Published: January 2020

AbstractBackground: Pheochromocytoma is a rare cause of hypertension resulting from increased catecholamine secretion. We aimed to develop a method to measure unconjugated plasma normetanephrine (NMN) and metanephrine (MN) without interference from acetaminophen, a widely prescribed drug for headaches.Methods: Plasma samples were obtained from 48 subjects (23 males, 25 females; mean age, 49 ± 14 years; hypertension, n = 37) under resting conditions. Following extraction on solid-phase cation-exchange columns, unconjugated metanephrines were analyzed by HPLC with electrochemical detection and with 4-hydroxy-3-methoxybenzylamine as an internal standard. Catecholamines were measured by HPLC.Results: The assays were linear up to 2000 pg for NMN and for MN. Intraassay imprecisions (CVs) were 4.7% for NMN and 7.0% for MN, and the interassay CV was 12% for both NMN and MN. The limit of detection was 11 fmol for NMN and 17 fmol for MN. Ingestion of acetaminophen or its addition to plasma did not interfere with the MN peaks. Plasma NMN and MN were positively correlated (r = 0.52 and 0.49, respectively; P &lt;0.01 for both) with the respective catecholamines. Plasma NMN (r = 0.27; P = 0.02) but not MN positively correlated with age, whereas only plasma catecholamines (and not metanephrines) were positively correlated (P &lt;0.05) with diastolic blood pressure.Conclusions: This sensitive MN assay is not affected by simultaneous acetaminophen medication, and reveals a correlation of metanephrines with plasma and urinary catecholamines and age but not with blood pressure.
Nitric Oxide Measurements during Endotoxemia
Authors: Brovkovych Viktor , Dobrucki Lawrence W , Brovkovych Svitlana , Dobrucki Iwona , Kalinowski Leszek , Kiechle Frederick , Malinski Tadeusz 
Published: January 2020

Abstract
Background: Excessive continuous NO release from inducible NO synthase over prolonged periods under pathological conditions, such as endotoxemia, contributes significantly to circulatory failure, hypotension, and septic shock. This NO production during endotoxemia is accompanied by superoxide release, which contributes to the fast decay of NO. Therefore, the amount of NO that diffuses to target sites may be much lower than the total amount released under pathological conditions.
Methods: We performed in vivo and ex vivo measurements of NO (electrochemical) and ex vivo in situ measurements of superoxide, peroxynitrite (chemiluminescence), and nitrite and nitrate (ultraviolet-visible spectroscopy). We determined the effect of lipopolysaccharide administration (20 mg/kg) on diffusible NO, total NO (diffusible plus consumed in chemical reactions), and superoxide and peroxynitrite release in the pulmonary arteries of rats.
Results: An increase in diffusible NO generated by constitutive NO synthase was observed immediately after administration of lipopolysaccharide, reaching a plateau (145 ± 18 nmol/L) after 540 ± 25 s. The plateau was followed by a decrease in NO concentration and its subsequent gradual increase after 45 min because of NO production by inducible NO synthase. The concentration of superoxide increased from 16 ± 2 nmol/L to 30 ± 3 nmol/L after 1 h and reached a plateau of 41 ± 4 nmol/L after 6 h. In contrast to the periodic changes in the concentration of diffusible NO, the total concentration of NO measured as a sum of nitrite and nitrate increased steadily during the entire period of endotoxemia, from 2.8 ± 0.2 μmol/L to 10 ± 1.8 μmol/L.
Conclusions: The direct measurement of NO concentrations in the rat pulmonary artery demonstrates dynamic changes throughout endotoxemia, which are related to the production of superoxide and the subsequent increase in peroxynitrite. Monitoring endotoxemia with total nitrate plus nitrite is not sensitive to these fluctuations in NO concentration.
Disappearance Rate of Catecholamines, Total Metanephrines, and Neuropeptide Y from the Plasma of Patients after Resection of Pheochromocytoma
Authors: Grouzmann Eric , Fathi Marc , Gillet Michel , de Torrenté Antoine , Cavadas Claudia , Brunner Hans , Buclin Thierry 
Published: January 2020

Abstract
Background: Plasma free metanephrines are a more reliable analyte to measure than catecholamines for the biochemical diagnosis of pheochromocytomas. We hypothesized that the long persistence of total (sulfate-conjugated plus free) metanephrines in the blood might have a significant diagnostic value.
Methods: We measured plasma concentrations of catecholamines and total metanephrines (sulfate-conjugated plus free forms) by HPLC with amperometric detection, and neuropeptide Y (NPY) by an amplified ELISA in seven patients before and after removal of their pheochromocytomas. The results for catecholamine, total metanephrines, and NPY in each patient were analyzed for up to 120 min, starting from the time of tumor vessel clamping. The persistence of analytes was quantified as the area under the concentration–time curve over 120 min.
Results: On the basis of the upper reference limit for each variable, plasma free norepinephrine (NE) and epinephrine (E) concentrations were increased preoperatively in at least one sample in seven and six patients, respectively. Total normetanephrine (NMN) and metanephrine (MN) were increased in all samples in seven and six patients, respectively. NPY was increased 2- to 465-fold. After removal of the tumor, MN and NMN showed a higher average relative increase above the upper limit of the reference interval than NE and E (P = 0.05), whereas NPY was intermediate. The persistence of increased values was significantly shorter for catecholamines than for metanephrines. The half-life estimated by nonlinear regression was 12.3 ± 7.8 min for NPY. Significant correlations were observed among NE, E, NMN, MN, and NPY concentrations, but parent markers (E and MN or NE and NMN) did not appear significantly intercorrelated.
Conclusions: A larger increase and a longer persistence of total metanephrines (reflecting predominantly sulfo-conjugated metanephrines) than catecholamines and NPY in plasma may contribute to their greater diagnostic accuracy in pheochromocytoma.
Total Homocysteine, Vitamin B12, and Total Antioxidant Status in Vegetarians
Authors: Herrmann Wolfgang , Schorr Heike , Purschwitz Kathrin , Rassoul Fausi , Richter Volker 
Published: January 2020

AbstractBackground: Decreasing or eliminating animal products from the diet decreases the intake of some essential nutrients, such as vitamin B12, which may lead to hyperhomocysteinemia. We investigated vitamin B12-dependent metabolism and oxidative stress in groups with various or no intake of meat or animal products.Methods: We investigated 44 high meat eaters, 19 low meat eaters, 34 lacto-ovo/lacto vegetarians, and 7 vegan vegetarians. Homocysteine (HCY) was assayed by HPLC, methylmalonic acid (MMA) by capillary gas chromatography–mass spectrometry, serum folate and vitamin B12 with a chemiluminescence immunoassay, and total antioxidant status (TAS) by a Randox method.Results: The mean serum HCY concentration of vegetarians was significantly increased, and in vegans the median concentration exceeded 15 μmol/L. Vegetarians had a higher serum concentration of MMA but a lower TAS. Vitamin B12 and folate did not differ significantly between vegetarian and omnivorous subjects. Overall, HCY and MMA were significantly correlated. Vitamin B12 correlated negatively with MMA, HCY, and folate, whereas the correlation with TAS was positive. Backward regression analysis revealed an independent influence of MMA on HCY, of HCY and vitamin B12 on MMA, and of vitamin B12 on TAS. The increased MMA concentration suggested a 25% frequency of functional vitamin B12 deficiency in all vegetarians. Serum vitamin B12 was below the lower reference limit in only five subjects.Conclusions: Functional vitamin B12 deficiency in vegetarians may contribute to hyperhomocysteinemia and decreased TAS, which may partly counteract the beneficial lifestyle of vegetarians. However, increased serum HCY is most likely not responsible for the lower TAS values in vegetarians. We recommend assaying of MMA and HCY to investigate functional vitamin B12 status.
Development of a Dual Monoclonal Antibody Immunoassay for Total Human Kallikrein 2
Authors: Finlay Judith A , Day John R , Evans Cindy L , Carlson Robert , Kuus-Reichel Kristine , Millar Lisa S , Mikolajczyk Stephen D , Goodmanson Marcia , Klee George G , Rittenhouse Harry G 
Published: January 2020

AbstractBackground: Human kallikrein 2 (hK2) shares 80% sequence identity with prostate-specific antigen (PSA). Because both hK2 and hK2-α1-antichymotrypsin (hK2-ACT) complexes have been identified in patient sera, we devised an immunoassay for total hK2 [(thK2); hK2 and hK2-ACT] and evaluated it in healthy subjects and patients with prostate disease.Methods: We developed monoclonal antibodies (mAbs) with high specificity for hK2 and hK2-ACT and minimal cross-reactivity to PSA. Using these mAbs, a sandwich assay was developed and its specificity for forms of hK2 was assessed. Serum samples (n = 1035) from healthy volunteers, patients with increased PSA, and men who had undergone radical prostatectomy were assayed for thK2. We also measured thK2 in samples before and after storage under common laboratory conditions.Results: The minimum detectable concentration in the thK2 assay was 0.008 μg/L, and PSA cross-reactivity was &lt;0.001%. The assay detected prohK2 and three different hK2–serum protease complexes. The median serum concentration of thK2 in control samples (0.013 μg/L) was significantly lower than the median in samples from patients with increased PSA concentrations (0.085 μg/L). Immunoreactive hK2 changed little in samples stored for up to 1 month at −70 °C.Conclusions: The thK2 assay recognizes all forms of hK2 that have been found in bodily fluids to date.
Enhanced Susceptibility to Oxidation and Diminished Vitamin E Content of LDL from Patients with Stable Coronary Artery Disease
Authors: Haidari Mehran , Javadi Ebrahim , Kadkhodaee Mehry , Sanati Arashmidos 
Published: January 2020

AbstractBackground: Convincing evidence points to oxidative modification of LDL as an important trigger in a complex chain of events leading to atherosclerosis. We investigated the occurrence of enhanced susceptibility of LDL to oxidation and decreased vitamin E concentration in LDL as additional risk factors promoting atherosclerosis among patients with established coronary artery disease (CAD).Methods: We examined 132 patients with angiographically confirmed CAD and compared them with 111 healthy control individuals. We measured conjugated diene production to assess susceptibility of LDL to copper-mediated oxidation. Vitamin E content of LDL was measured by HPLC.Results: The mean lag time of LDL oxidation and LDL α-tocopherol/LDL-cholesterol ratio were lower in the patients with CAD (55 ± 14 min and 2.4 ± 1.0 mmol/mmol) than in the controls (63 ± 13 min and 2.9 ± 1.1 mmol/mmol; P &lt;0.0001 and &lt;0.001, respectively). Multiple stepwise regression analysis demonstrated the lag time (odds ratio, 1.96; 95% confidence interval, 1.34–2.87; P &lt;0.0001) and concentration of vitamin E in LDL (odds ratio, 1.65; 95% confidence interval, 1.16–2.33; P &lt;0.005) as independent determinants of CAD. Significant inverse Spearman rank correlations were found between lag time (r = −0.285; P &lt;0.001) or concentration of vitamin E in LDL (r = −0.197; P &lt;0.002) and severity of CAD. Lag times were not significantly correlated with serum C-reactive protein or ferritin.Conclusions: Our data suggest that a short LDL oxidation lag time and a low concentration of vitamin E in LDL might be independent coronary risk factors for stable CAD in Iranian people.
Tumor Necrosis Factor-α in Serum of Patients with Inflammatory Bowel Disease as Measured by a Highly Sensitive Immuno-PCR
Authors: Komatsu Momoko , Kobayashi Daisuke , Saito Kaori , Furuya Daisuke , Yagihashi Atsuhito , Araake Hiroshi , Tsuji Naoki , Sakamaki Sumio , Niitsu Yoshiro , Watanabe Naoki 
Published: January 2020

AbstractBackground: The significance of serum concentrations of tumor necrosis factor-α (TNF-α) in the pathogenesis of inflammatory bowel disease (IBD) is uncertain. We measured TNF-α in serum from IBD patients by immuno-PCR to analyze the relationship between TNF-α and pathophysiologic state in IBD.Methods: Serum samples were collected from 54 healthy blood donors, 29 patients with ulcerative colitis (UC; 46 samples), and 7 patients with Crohn disease (CD; 8 samples). DNA label was generated by PCR amplification using biotinylated primer and was bound with streptavidin to biotinylated third antibody. TNF-α sandwiched by antibodies was detected by PCR amplification of the DNA label.Results: TNF-α could be measured in all samples. The median serum concentration in IBD patients overall was ∼390-fold higher than in healthy donors (median increase, 380-fold for UC, 640-fold for CD). The median serum TNF-α concentration was 1.7-fold higher in the active stage of UC than in the inactive stage (P &lt;0.05), and this difference could be detected in individual patients.Conclusions: Sensitive measurement of serum TNF-α could provide an important pathophysiologic marker for the presence and activity of IBD.
Neonatal Screening for Galactosemia by Quantitative Analysis of Hexose Monophosphates Using Tandem Mass Spectrometry: A Retrospective Study
Authors: Jensen Ulrich Glümer , Brandt Niels Jacob , Christensen Ernst , Skovby Flemming , Nørgaard-Pedersen Bent , Simonsen Henrik 
Published: January 2020

AbstractBackground: Classic galactosemia (OMIM 230400) is an inherited disorder in the metabolism of galactose caused by deficiency of the enzyme galactose 1-phosphate uridyl transferase (EC 2.7.7.12). Galactosemia leads to accumulation of galactose and galactose 1-phosphate (gal-1-P) in blood and tissues and, if untreated, produces neonatal death or severe mental retardation, cirrhosis of the liver, and cataracts. Hence, the disorder is included in many neonatal screening programs.Methods: We retrospectively analyzed filter-paper blood samples obtained 4–8 days postpartum for routine neonatal screening from 12 galactosemia patients and 2055 random controls. Total hexose monophosphates (HMPs) were used as a marker of gal-1-P and were assayed by negative-ion mode electrospray tandem mass spectrometry (tandem MS) with settings biased toward gal-1-P detection. The predominant precursor/product ion pair m/z 259/79 was used to quantify total HMPs by external standardization.Results: Linear calibration curves were obtained in the range 0–8 mmol/L gal-1-P. The detection limit was 0.1 mmol/L HMP, and total CVs ranged from 13% at the detection limit to &lt;8% at &gt;1 mmol/L HMP. The method was in agreement with an alkaline phosphatase-galactose dehydrogenase method. All samples from galactosemia patients contained increased HMP concentrations (range for patients, 2.6–5.2 mmol/L; range for reference group, &lt;0.10–0.94 mmol/L). The diagnostic sensitivity and specificity were 100% at a cutoff of 1.2 mmol/L HMP. A Duarte/classic galactosemia compound heterozygous sample could be discriminated clearly from both patient and reference samples.Conclusion: Quantitative analysis of HMPs by tandem MS can be used in laboratory investigations of galactosemia.
Plasma Homocysteine Is Not Subject to Seasonal Variation
Authors: McKinley Michelle C , Strain J J , McPartlin Joseph , Scott John M , McNulty Helene 
Published: January 2020

Abstract
Background: Studies investigating the relationship between plasma total homocysteine (tHcy) and vascular disease usually rely on a single measurement. Little information is available, however, on the seasonal variability of plasma tHcy. The aim of this study was to investigate the seasonal variation in fasting plasma tHcy and related B-vitamin intake and status in a group of people who did not consume fortified foods or take B-vitamin supplements.
Methods: In this longitudinal study, a group of 22 healthy people were followed for 1 year. A fasting blood sample and dietary information were collected from each individual every 3 months, i.e., at the end of each season.
Results: There was no significant seasonal variation in plasma tHcy or in B-vitamin intake or status with the exception of red cell folate (significantly lower in spring compared with autumn or winter) and serum folate (significantly lower in spring compared with the other seasons). Although the between-person variation in plasma tHcy was high (47%), the within-person variation was low (11%). This low variation, combined with the low methodologic imprecision of 3.8%, yielded a high reliability coefficient for plasma tHcy (0.97).
Conclusions: Although there was a small seasonal variation in folate status, there was no corresponding seasonal variation in plasma tHcy. The high reliability coefficient for plasma tHcy suggests that a single measurement is reflective of an individual’s average plasma tHcy concentration, thus indicating its usefulness as a potential predictor of disease. This, however, needs to be confirmed in different subgroups of the population.