bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of Radiation and Chemotherapy-Related DNA Strand Breaks on Carcinogenesis: An Evaluation
Authors: Froelich Jens J. , Schneller Folker R. G. , Zahn Rudolf K. 
Published: October 2004

Abstract
Purpose: DNA strand breaks are believed to induce carcinogenesis. This study was conducted to analyze induction and repair of irradiation- and chemotherapy-related strand breaks in vitro.
Methods: Friend Leukemia cells were exposed to irradiation and various chemotherapeutic agents at different doses and concentrations. Occurence of strand breaks was determined fluorometrically, measuring the rate of DNA unwinding immediatly after exposure and 24 hours later.
Results: The amount of double-stranded DNA decreased significantly for irradiation, doxorubicin, dactinomycin and etoposide (p ≤ 0.05, t-test). After 24 hours free of exposure, the persistent damage was detectable for all of these agents but not for irradiated cells, with DNA strand breaks being decreased for etoposide, unchanged for doxorubicin and increased for methotrexate as well as for dactinomycin.
Conclusions: Severe DNA damage is induced by various chemotherapeutic agents and by irradiation. While repair of chemotherapy-related strand breaks may remain incomplete or prolonged for some chemotherapeutic agents, repair of radiation induced strand breaks is faster and more complete. Therefore chemotherapy-related carcinogenesis may partially be explained by prolonged persistence of DNA strand breaks.
Endothelin-1- and Endothelin-Receptors in Lung Biopsies of Patients with Pulmonary Hypertension due to Congenital Heart Disease
Authors: Lutz Jens , Gorenflo Matthias , Habighorst Matthias , Vogel Martin , Lange Peter E. , Hocher Berthold 
Published: October 2004

Abstract
Endothelin-1 (ET-1), with its vasoconstrictive and proliferation-stimulating effects, could play a role in the pathogenesis of primary pulmonary hypertension. We investigated the relationship between the ET-1 like immunoreactivity and the ET-receptor density, the grade of the pulmonary vasculopathy, and properties of the pulmonary circulation in patients with pulmonary hypertension due to congenital heart disease.
Twenty-six patients with a median age of 1 year and 1 month (6 weeks–17 years–9 months) were assigned to group I (n = 15) with a pulmonary to systemic flow ratio (Qp/Qs) ≥ 1.5 and a pulmonary to systemic resistance ratio (Rp/Rs) ≤ 0.3 (“high flow–low resistance group”) and to group II (n = 11) with a Qp/Qs < 1.5 and an Rp/Rs > 0.3 (“low flow–high resistance group”).
Patients belonging to group II showed a higher ETA-receptor density in lung arteries (p < 0.05) and parenchyma (p < 0.01) than patients in group I. Patients with the highest ET-1 like immunoreactivity in lung artery walls also showed a trend towards a higher ETA-receptor density. The ETB-receptor expression was low and not related to any of the above factors.
Our results suggest that the paracrine lung ET-1 system is up-regulated in pediatric patients with secondary pulmonary hypertension associated with congenital heart disease.
Biomarkers of Bone Turnover and Bone Mineral Density in Hyperprolactinemic Amenorrheic Women
Authors: Shaarawy Mohamed , El-Dawakhly Abdel-Salam , Mosaad Medhat , El-Sadek Mostafa Mohamed 
Published: October 2004

Abstract
We tested the hypothesis that biomarkers of bone resorption are increased in hyperprolactinemic amenorrheic patients with estrogen (E) deficiency, augmenting the possible risk of developing osteoporosis. Fifty hyperprolactinemic patients with amenorrhea of more than 12 months and with low serum E2, as well as 30 healthy fertile women (controls), matched for age and body mass index, participated in this study. Bromocriptine was administered orally to hyperprolactinemic patients and blood and urine samples were collected before and 12 weeks after treatment. Serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP), reflecting bone formation, and urinary deoxypridinoline (D-Pyr) and N-telopeptide of type 1 collagen (NTX) excretion, reflecting bone resorption, were measured using direct immunoassays. Hyperprolactinemic patients had higher (p < 0.0005) levels of all the biomarkers compared to control values: (OC, 22 ± 1.2 [SE] vs. 14 ± 0.99 ng/ml (+57 %); B-ALP, 14.2 ± 0.7 vs. 7.5 ± 0.8 ng/ml (+89 %); D-Pyr, 8.8 ± 0.6 vs. 3.2 ± 0.3 nmol/mmol creatinine (+175 %) and NTX, 65 ± 5.1 vs. 25 ± 3.2 nmol bone collagen equivalent (BCE)/mmol creatinine (+160 %)). These results were associated with significantly decreased lumbar spine bone mineral density (LS-BMD), measured by dual energy X-ray absorptiometry (DEXA). Treatment of hyperprolactinemia with bromocriptine restored normal values of bone formation and resorption markers. In conclusion, hyperprolactinemia with estrogen deficiency exhibits a significant increase of bone resorption which is associated with a significant decrease of LS-BMD. These changes may subject the patient to the possible risk of developing osteoporosis.
Serum Ionized Magnesium: Comparison of Results Obtained with Three Ion-Selective Analyzers
Authors: Huijgen Henk J. , Sanders Renata , Cecco Stacey A. , Rehak Nadja N. , Sanders Gerard T. , Elin Ronald J. 
Published: October 2004

Abstract
In a two-center (Academic Medical Center, The Netherlands, and National Institutes of Health, USA) study, we compared ionized magnesium (iMg2+) results in serum determined with the AVL 988/4, KONE Microlyte 6 and NOVA CRT, which are the currently available analyzers equipped with a magnesium ion-selective electrode. The comparison was performed with frozen serum samples from normal individuals and patients. Imprecision and reference intervals were established. We found the best agreement between the KONE(x) and AVL(y) magnesium ion-selective electrodes (y = 0.972x−0.013; n = 138) with samples from patients. With samples from normals, all three analyzers reported significantly different results (p < 0.05). Best precision was found using the NOVA; coefficients of variation established at three levels were all < 4.0%. Coefficients of variation for the AVL and KONE were < 5% at normal and high iMg2+, but 10.7 and 9.4%, respectively, at iMg2+ ≈ 0.30 mmol/l. The reference intervals (mean ± standard deviation) based on measurements in fresh serum samples were different for each analyzer: 0.55–0.63 mmol/l for AVL, 0.470.57 mmol/l for KONE and 0.43–0.55 mmol/l for NOVA. Thus, significant differences among the ionized magnesium concentration obtained with the three analyzers, limit comparison of results in clinical practice, and need to be resolved (e.g. by improvement of specificity and standardization of calibrators).
Recent Activities of EC4 in the Harmonization of Clinical Chemistry in the European Union
Authors: Sanders Gerard T. , Jansen Rob T. , Beastall Graham , Gurr Eberhard , Kenny Desmond , Kohse Klaus P. , Zérah Simone 
Published: October 2004

Abstract
This article describes the recent activities of the European Communities Confederation of Clinical Chemistry (EC4). Main goal of EC4 is harmonization of clinical chemistry in the European Union and Europe. EC4's actions connected to that are training and registration of professionals, and accreditation of laboratories. The 35000 professionals practising clinical chemistry in the EU have different backgrounds (medical, pharmaceutical, science-oriented, veterinary, or microbiological). Thus, for the harmonization of training of clinical chemists, EC4 has published a European Syllabus for Postgraduate Training, and instituted a European Union Register for Clinical Chemists. The Syllabus is an indication of the level of requirements in postgraduate training. The EC4 initiative to implement the European Register for Clinical Chemists is based on the 8 years vocational training necessary to obtain sufficient knowledge in clinical chemistry according to the European Syllabus. A guide to the EC4 Register has been published; registration leads to the title European Clinical Chemist (EurClinChem). The accreditation of laboratories must be based on a total quality management system. EC4 has described guidelines (essential criteria) which it judges appropriate for establishing the quality of medical laboratory service; it does not wish to fulfil the role of an accrediting body. Moreover, a working group has been set up to seek to harmonize the work of national accrediting bodies. Therefore, it is logical that EC4 monitors the activities of the different standardizing bodies that might influence the practice of clinical chemistry in the EU. Finally, some aspects concerning the future strategy of EC4 are brought forward.
Inflammation, the Acute Phase Response and Atherosclerosis
Authors: Whicher John , Biasucci Luigi , Rifai Nader 
Published: October 2004

AbstractThere is increasing evidence that atherosclerosis is a chronic inflammatory disorder resulting from a combination of processes, and that acute exacerbations of this inflammation are associated with the acute coronary syndromes such as myocardial infarction and unstable angina. Measurement of the serum level of acute phase proteins, such as C-reactive protein and serum amyloid A protein, has been used to predict the risk of acute events in patients with atherosclerosis. Prospective studies have shown that higher serum acute phase protein levels, often within the reference range, are associated with increased risk of myocardial infarction (MI), stroke or peripheral vascular disease and predict risk of infarction and death among high-risk patients. These observations have important implications for the assessment of patients and for treatment.
Characterization of Two Distinct Mechanisms for Induction of Apoptosis in Human Vascular Endothelial Cells
Authors: Gräfe Michael , Steinheider Gerhard , Desaga Ulrike , Warnecke Christina , Lehmkuhl Hans B. , Regitz-Zagrosek Vera , Hildebrandt Alfred G. , Fleck Eckart 
Published: October 2004

AbstractTissue homeostasis is fundamentally influenced by the functional integrity and state of endothelial cells. Survival and death of endothelial cells are encountered in cardiovascular disease and may, moreover, affect and determine the development of atherosclerosis and restenosis following intracoronary therapeutical interventions.Apoptosis was studied in cultured human umbilical vein endothelial cells (HUVEC) to investigate the regulation of endothelial cell death following serum/growth factor depletion as well as incubation with actinomycin-D.Apoptosis was verified by DNA fragmentation and quantified by fluorescence activated cell sorting (FACS) analysis after TdT-mediated deoxyuridine-triphosphate nick end-labeling (TUNEL). An ELISA was used for detecting intracytoplasmatic nucleosomes. Untreated HUVEC showed 16 ± 6 % TUNEL positive cells after 24 hours as analyzed by FACS. Serum/growth factor depletion increased apoptosis by 79 ± 7%, while 50 ng/ml of the pro-apoptotic drug actinomycin-D induced comparable effects (72 ± 11% ). Apoptosis by serum/growth factor depletion could be blocked completely by the anti-apoptotic agent cycloheximide (2 μg/ml), but was ineffective in blocking actinomycin-D-induced apoptosis. Pyrrolidine dithiocarbamate (PDTC) also acted as an anti-apoptotic agent by blocking apoptosis induced by actinomycin-D, but had no effect on apoptosis induced by factor depletion.Thus, two independent mechanisms for regulation of apoptosis are suggested to be present in human vascular endothelial cells.
Lipid Peroxidation and Antioxidant Defenses in Cystic Fibrosis Patients
Authors: Benabdeslam Hassiba , Abidi Hassane , Garcia Isabelle , Bellon Gabriel , Gilly Robert , Revol André 
Published: October 2004

Abstract
Lipid peroxidation biomarkers and antioxidant status were measured in 76 cystic fibrosis (CF) patients and compared to 40 control subjects. Univariate and multivariate statistics were performed in this study. Results showed that indicators of lipid peroxidation were higher in CF patients than in controls; thiobarbituric acid reactants and autoantibodies against oxidized low-density lipoproteins were significantly increased in CF patients. Red blood cells and whole blood glutathione peroxidase activities were lower in CF patients than in controls. No difference in red blood cell superoxide dismutase activity was observed. Measured concentration of glutathione peroxidase in plasma showed a higher mean value of this protein in CF patients than in controls. Retinol, α-tocopherol and β-carotene concentrations were all reduced in CF patients as compared to controls; this was particularly pronounced for β-carotene. The decreased α-tocopherol concentration was associated with higher percent hemolysis in CF patients. The results of this study indicate that both lipid peroxidation biomarkers and antioxidant status were disturbed in CF patients, despite medical assistance. Measures of oxidative stress parameters, such as thiobarbituric acid reactants, glutathione peroxidase, and β-carotene concentrations can be considered as significant indicators to discriminate CF patients and control subjects.
Advances in Reverse Transcription Polymerase Chain Reaction Analysis of Cellular mRNA Levels of Transforming Growth Factor-β1 by Capillary Electrophoresis with Laser-Induced Fluorescence Detection
Authors: Beck Alexander , Lehmann Rainer , Gambaro Giovanni , Häring Hans-Ulrich , Schleicher Erwin D. , Voelter Wolfgang , Ceol Monica 
Published: October 2004

Abstract
The prosclerotic transforming growth factor β1 (TGF-β1) is a key factor in the induction and maintenance of fibrosis in different organs. To assess relative changes in TGF-β1 mRNA levels, the comparative kinetic reverse transcription-polymerase chain reaction strategy was used. In this method, cellular mRNA levels of the target and a house-keeping gene are reverse transcribed, amplified by the polymerase chain reaction (PCR) and the kinetics of PCR amplification are compared. Since the current determination of the PCR products, using electrophoretic separation in polyacrylamide gel, staining and scanning of the gel, is timeconsuming (≥ 5 hours) and inaccurate, we have developed a method using capillary gel electrophoresis (CGE) in combination with laser-induced fluorescence (LIF) detection for quantification of PCR-products. Using the CGE-LIF method, a minute aliquot of the PCR reaction mixture is separated and quantified within 10 min. Comparison of the values with those obtained by polyacrylamide gel electrophoresis demonstrates the improved sensitivity (> 1000 fold) and accuracy of the proposed method. The CGE-LIF procedure offers a convenient way of automated, comparative analysis of low levels of mRNA via reverse transcription PCR in low cell numbers or small amounts of tissue samples.
Physiological HEPES Buffer Proposed as a Calibrator for pH Measurement in Human Blood
Authors: Lang Werner , Zander Rolf 
Published: October 2004

Abstract
N-(2-hydroxyethyl)-piperazine-N'-2-ethanesulfonic acid, known as HEPES buffer, with p K in the physiological range was studied for use as an alternative to conventional phosphate buffer for the calibration of pH in modern clinical analyzers. In different series of aqueous equimolar HEPES buffer, pH was measured at 37 °C with a capillary glass electrode standardized previously using phosphate, and variations due to changes in total HEPES buffer concentration (0.025 to 0.320 mol/l), and NaCl (0 to 0.250 mol/l) were monitored. For 0.05 equimolar HEPES buffer without NaCl, the pH of 7.362 ± 0.003 (n = 15) obtained coincided well with the reference pH (7.364) from the National Institute of Standards and Technology (NIST). In particular, in the preferred 0.05 equimolar HEPES buffer/0.110 mol/l NaCl, which is isotonic to human plasma (0.160 mol/l), and termed physiological HEPES buffer (PHB), the pH of 7.346 ± 0.003 (n = 84) can be related to the calculated corresponding reference pH from NIST without liquid junction (7.374), and is also compatible with the pH measured in normal arterial blood, pH = 7.403 ± 0.003 (n = 20). Hence, in the two-point calibration of clinical analyzers, PHB, which is defined operationally with respect to the glass electrode and to phosphate buffer, may be useful as a calibrator in the range of buffer adjustment control to meet the correct values for pH when measuring in blood.
Whereas Na-HEPES salt is hygroscopic and does not meet the declared purity grade (> 99 %), pure HEPES acid is non-hygroscopic and conforms to the manufacturer's purity grade (≥ 99 %). Therefore, for easy preparation of PHB, HEPES acid is the preferred starting material.
Towards Common Reference Intervals in Clinical Chemistry
Authors: Bäck Sten-Erik , Nilsson Jan-Erik , Fex Göran , Jeppson Jan-Olof , Rosén Ulf , Tryding Nils , von Schenck Henning , Norlund Lena 
Published: October 2004

Abstract
The population sample of the Kristianstad survey, a reference intervals survey in the county of Kristanstad, was used to establish new reference intervals in clinical chemistry at the laboratories of the Central Hospital in Kristianstad, the University Hospital in Lund and the University Hospital in Malmö.
Three-hundred and fifty nine subjects, male and female, aged 20–80+ years, were invited to participate in the study, with a participation rate of 70 %. Up to 70 analyses were performed on each subject, general clinical chemistry parameters in all three laboratories, specialized analyses where available. Separate a priori exclusion criteria were defined for each test. In addition, the test pattern of each individual was evaluated for signs of preclinical disease. Twelve cases of preclinical disease were discovered and clinically confirmed.
Details on all test methods are presented along with information concerning instruments used, calibration procedures, methods of calculation and obtained reference intervals. Although the methods were in general calibrated against acknowledged reference materials, in some instances differences were found that made common reference intervals across all laboratories impossible.
Problems relating to the practical use of international recommendations and the establishment of reliable reference intervals are discussed.
Evaluation of an Automated Method for Cytokine Measurement Using the Immulite® Immunoassay System
Authors: Berthier Franck , Lambert Claude , Genin Chrisitian , Bienvenu Jacques 
Published: October 2004

Abstract
Cytokines are key mediators in cell regulation and communication. The concentration of these proteins can rapidly and importantly increase during severe clinical situations. However, current techniques are not adapted to stat measurement, thus making their clinical use limited.
In this context, the commercialization of five new kits for cytokine measurement interleukin ((IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-α and IL-2R) on an automated immunoanalyzer, the Immulite®, seems to be a new approach for the determination of these markers. We report here the evaluation of the performance of these tests. The technique is based on a solid phase (bead) two site chemiluminescent enzyme immunometric assay. The analysis is performed within 60 to 90 minutes and the calibration is stable for 15 days.
The values of the between-run imprecision study were similar to those from the within-run study with coefficients of variation (CV) ranging from 2% (low values of IL-8) to 11.5 % for intermediate concentrations of IL-6 (500 pg/ml). CVs were usually around 5%.
The accuracy was determined by a linearity study using standards (except for IL-2R) provided by the National Institute for Biological Standards and Control (NIBSC). Slopes obtained during this study were close to 1 (r2 = 0.99), except for IL-6, for which the slope was 1.55. TNF-α values were close to those expected. IL-1 results were about 20 % higher. IL-6 values were over estimated above 100 pg/ml and under estimated below this value. IL-8 study seemed to be impaired by the poor stability of this molecule in the NIBSC preparation. Correlation study with standard laboratory techniques gave variable results : for IL-1 (n = 43) the slope was 0.77 (study carried out using cell culture media), for IL-6 (n = 54) the slope was 0.78, for IL-8 (n = 37) the slope was 1.64, for TNF-α (n = 40) the slope was 0.33 and the slope for IL-2R (n = 51) was 5.1. For the last cytokine, the unit in Immulite assay was different from the one used in our comparison technique. Cross-calibration results were consistent with these data and show that the bias is probably linked to a calibration problem.
The study demonstrated excellent practicality of the system, and good stability of the calibration curve (15 days). However, the sample volume required (350 μl for the IL-6 and the TNF-α) could constitute a limitation for pediatric measurements.
Characterization of Monoclonal Antibodies to Human Protein 1/Clara Cell 10 Kilodalton Protein
Authors: Yamaguchi Tetsuji , Yamada Toshiyuki , Okutani Ryuta , Shijubo Noriharu , Singh Gurmukh , Itoh Yoshihisa 
Published: October 2004

AbstractHuman protein 1/Clara cellMr10 000 protein consists of two identical subunits of seventy amino acid residues each. In the present study, eight clones of monoclonal antibodies against native protein 1 were prepared and their respective epitopes were immunochemically and immunohistochemically characterized using native protein 1, truncated recombinant protein 1 and synthesized peptides. Among the clones, three designated as TY-5, TY-7 and TY-8 recognized amino acid residues 7–16, residues 19–28, and residues 39–46, respectively, all of which comprise the hydrophobic cavity of protein 1, possibly associated with chemical binding function. With the exception of TY-4, the remaining clones recognized residues 61–68 which are exposed to solvent. The epitope of TY-4 remains undetermined. Proper selection and combination of clones and recombinant protein 1 may be useful for fundamental and clinical studies of protein 1.
Assessment of Package Inserts for Diagnostic Kits
Authors: Secchiero Sandra , Sciacovelli Laura , Bonvicini Piero , Zaninotto Martina , Plebani Mario 
Published: October 2004

Abstract
To assure the quality of service in laboratory medicine, it is necessary to implement a quality system which comprises the entire testing process. The use of quality reagents is an important aspect of the process. Despite the fact that it is the responsibility of the laboratory to ensure the quality of the analytical system (including reagents) and since it is impossible to evaluate all commercial diagnostic kits, the laboratory often depends on statements issued by the manufacturer to select the most appropriate diagnostics for a particular laboratory.
In this study we report the results of the analysis of information provided in 887 package inserts enclosed in the more widely used commercial diagnostic kits, following the Standard for the labelling of clinical laboratory materials of the European Committee for Clinical Laboratory Standards (ECCLS). Only a third of these were in agreement with the guidelines of ECCLS Standard, reporting complete and correct information. We believe that it is necessary to implement a constructive cooperation between manufacturers of diagnostic materials and clinical laboratories to produce a more uniform approach to improvements in laboratory quality assurance.