bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Clinical Trial of the Immunocytokine EMD 273063 in Melanoma Patients
Authors: King David M. , Albertini Mark R. , Schalch Heidi , Hank Jacquelyn A. , Gan Jacek , Surfus Jean , Mahvi David , Schiller Joan H. , Warner Thomas , Kim KyungMann , Eickhoff Jens , Kendra Kari , Reisfeld Ralph , Gillies Stephen D. , Sondel Paul 
Published: October 2004

PurposeTo evaluate the safety, toxicity, in vivo immunologic activation, and maximum-tolerated dose (MTD) of EMD 273063 (hu14.18-IL-2) in patients with metastatic melanoma.Patients and MethodsThirty-three patients were treated with EMD 273063, a humanized anti-GD2 monoclonal antibody (mAb) linked to interleukin-2 (IL-2). EMD 273063 was given as a 4-hour intravenous infusion on days 1, 2, and 3 of week 1. Patients with stabilization or regression of disease could receive a second course of treatment at week 5. Dose levels evaluated were 0.8, 1.6, 3.2, 4.8, 6.0, and 7.5 mg/m2/d.ResultsNineteen of 33 patients completed course 1 with stable disease and went on to receive course 2. Eight patients had stable disease on completion of course 2. Grade 3 adverse events included hypophosphatemia (11 patients), hyperglycemia (three patients), hypotension (two patients), thrombocytopenia (one patient), hypoxia (three patients), elevated hepatic transaminases (two patients), and hyperbilirubinemia (one patient). Opioids were required for treatment-associated arthralgias and/or myalgias during 17 of 52 treatment courses. No grade 4 adverse events were observed. Dose-limiting toxicities at the MTD included hypoxia, hypotension, and elevations in AST/ALT. Grade 3 toxicities were anticipated based on prior studies of IL-2 or anti-GD2 mAbs, and all resolved. Immune activation was induced, as measured by lymphocytosis, increased peripheral-blood natural killer activity, and cell numbers, and increased serum levels of the soluble alpha chain of the IL-2 receptor complex.ConclusionTreatment with the immunocytokine EMD 273063 induced immune activation and was associated with reversible clinical toxicities at the MTD of 7.5 mg/m2/d in melanoma patients.
Primary Dental Care 1994–2004: The First Ten Years a Chronology
Authors: Renson Ted 
Published: October 2004

The prime purpose of a professional journal is to keep its readers informed of changes of importance affecting the practise of that profession. That is the criterion that I have applied in producing this chronology of the papers that have been published in Primary Dental Care during the past decade. The ambition which has guided me since I received the invitation to carry out this review is a simple one: to include as much as may generally be found useful by general dental practitioners (GDPs), who form the bulk of our readership. In 1789 the English philosopher Jeremy Bentham extolled the virtues of utility for mankind when he declared that ‘the greatest happiness of the greatest number is the foundation of morals and legislation’. The contributors that I have included, by contrast, think of their utilitarianism as striving after the most practical. The principal purpose of this chronology is to achieve a summary, without weighing causes or consequences. From past experience, an outstanding virtue of such an aggregated record is that it can inspire fresh patterns of thought and thus encourage the submission of manuscripts as a result of those thoughts. I can think of scarcely any facet of the general practice of dentistry that has not been touched upon, for the most part authoritatively. I hope that these brief aide-memoires may persuade old readers to return to those articles of particular interest to them and that new readers will feel informed about past papers. Every issue of the journal to date has been reviewed. Dates, volume and issue numbers and principal authors’ names are all included. With these identifying features any paper, to which reference is made, may be quickly found. It would be manifestly absurd to use precious space on a formal listing of more than 250 references and this listing has, therefore, been omitted.
Development of Molecular Genetics
Authors: Tahvanainen Esa 
Published: October 2004

AbstractHuman genetics has rapidly evolved from vague impression that descendants resemble their parents, to science which is now of utmost importance to the development of new principles and practice in medicine. It was only in the beginning of this century when it was suggested that chromosomes might carry genetic information. During the two last decades researchers have developed amazing methods to study and manipulate genes. This has created new possibilities to diagnose and cure diseases, but also raised ethical and legal questions. These developments are outlined in the present paper.
The Changing Face of Clinical Laboratories
Authors: Plebani Mario 
Published: October 2004

Abstract
Laboratory medicine has undergone a sea change, and medical laboratories must now adapt to, and meet new, customer-supplier needs springing from shifts in the patterns of disease prevalence, medical practice, and demographics. Managed care and other cost-containment processes have forced those involved in health care to cooperate to develop a full picture of patient care, and this has affected clinical laboratory objectives, the main focus now being on improvement in medical outcomes. More recently, the resource shortages in health care and results of cost/effectiveness analysis have demonstrated that the value of a laboratory test must be ascertained not only on the basis of its chemical or clinical performance characteristics, but also by its impact on patient management, the only true assessment of the quality of testing being quality of patient outcomes. The time is ripe for changing the vision of laboratory medicine, and some of the reasons for this are the availability of results in real-time, the introduction of more specific tests, and the trend to prevent diseases rather than cure them. The information from laboratory tests designed to evaluate biochemical or genetic risk and/or prognostic factors cannot be replaced either by physical examination and/or the assessment of symptoms. Today, the importance of laboratory scientists must be proven in three broad areas: a) guaranteeing the quality of tests, irrespective of where they are performed; b) improving the quality of the service; c) maximizing the impact of laboratory information on patient management.
Analysis of the Gly40Ser Polymorphism in the Glucagon Receptor Gene in a German Non-Insulin-Dependent Diabetes Mellitus Population
Authors: Ambrosch Andreas , Lobmann Ralf , Dierkes Jutta , König Wolfgang , Luley Claus , Lehnert Hendrik 
Published: October 2004

Abstract
A heterozygous polymorphism changing GGT40 (Gly) to AGT40 (Ser) in the glucagon receptor gene (GCG-R) was reported to be associated with non-insulin-dependent diabetes mellitus (NIDDM). A possible involvement of this polymorphism in impaired glucose tolerance was also suggested in a French population. However, the prevalence of this polymorphism differs markedly among different ethnic groups, whereby the results in German populations were found to be contradictory. We thus investigated the association of this mutation with NIDDM and healthy subjects in 508 German subjects (196 NIDDM, and 312 controls).
None of the control subjects, but one of the NIDDM patients demonstrated the Gly40Ser polymorphism. Since no first-degree relative of the index patient had this genetic variance, a de novo mutation is suggested. Although the frequency of the Gly40Ser polymorphism in NIDDM observed in France is not confirmed in our population, this genetic variance is also evident in Germany.
A Relationship between K-ras Gene Mutations and Some Clinical and Histologic Variables in Patients with Primary Colorectal Carcinoma
Authors: Beránek Martin , Bureš Jan , Palička Vladimír , Jandík Pavel , Langr František , Nejedlá Eliška 
Published: October 2004

Abstract
Mutations in the Kirsten ras 2 (K-ras) gene were described as early events in the process of colorectal carcinogenesis. The aim of this study was to find a possible relationship between the presence of K-ras mutation in samples of primary colorectal carcinomas and the clinico-pathological data of the investigated patients. Mutation in codon 12 of the K-ras gene was determined in 18 of 53 colorectal carcinomas (34 %) in our group of patients. The presence of K-ras gene mutations was not related to gender, age of subject at diagnosis, staging or cancer location (p > 0.05). Sixteen of the 42 (38 %) moderately differentiated carcinomas, and two of the eight (25 %) well differentiated carcinomas contained K-ras mutation in codon 12, but none of the three poorly differentiated carcinomas contained the mutation. Moderately differentiated tumours contained an aspartate code GAT (in eight cases), a valine code GTT (in six cases), an alanine code GCT (in one case) and a serine code AGT (in one case) in codon 12. Well differentiated tumours contained only the valine code GTT (two cases).
Our results show that the frequency of mutations in the K-ras gene in carcinomas in Central Europe is not different from the frequencies found in other parts of the world. The homogeneous incidence of K-ras mutation does not seem to be related to ethnic factors, dietary habits, or the composition of the diet.
Particle Counting Immunoassay for Urinary Cotinine. Comparison with Chromatography, Enzyme-linked Immunoassay and Fluorescence Polarization Immunoassay
Authors: Galanti Laurence M. , Dell'Omo Juliette , Vanbeckbergen Danielle , Dubois Pierre , Masson Pierre L. , Cambiaso César L. 
Published: October 2004

Abstract
Urinary cotinine was measured according to its inhibitory activity on the agglutination of cotinine-coated latex particles by anti-cotinine antibodies, the agglutination being measured by optical counting of the remaining non-agglutinated particles (particle counting, PaC). The detection limit was 0.03 μg/ml and the practical range extended from 0.03 to 3.9 μg/ml. The correlation results of 320 urine samples with those of high pressure liquid chromatography, enzyme-linked (Coti-Tracq EIA, Serex Inc., Maywood, NJ, USA), and fluorescence polarization immunoassay (TDX instrument, Abbott, Abbott Park, IL, USA) were r = 0.90, r = 0.69, r = 0.87, respectively, whereas the correlation coefficients between the assays other than particle counting ranged from 0.62 to 0.88. PaC does not require any separation step and can thus be easily automated.
Identification of IgG-specific Oligoclonal Banding in Serum and Cerebrospinal Fluid by Isoelectric Focusing: Description of a Simplified Method for the Diagnosis of Neurological Disorders
Authors: Marchetti P. , Gutierrez J. , Velia P. , Faucompré J.-L. , Onraed B. , Formstecher P. , Hennache B. 
Published: October 2004

Abstract
Clinical laboratory procedures using cerebrospinal fluid (CSF) to assist in the diagnosis of multiple sclerosis (MS) are based essentially on the determination of oligoclonal bands (OB) in CSF and not in serum. To date, the techniques using isoelectric focusing (IEF) have represented one of the most efficient methods for detecting supernumerary bands in CSF but unfortunately were not always compatible with a routine use. Here, we describe a revised method of IEF suitable for the diagnosis of neurological disorders. The kit-based technique was simplified and the present procedure allowed an easier execution, reduced the overall analysis time and permitted an uncomplicated intepretation of oligoclonal profiles. Moreover, the technique developed was very sensitive and specific for the diagnosis of MS diagnosis. In conclusion, the IEF protocol described in this report is suitable for OB detection in any laboratory.
Low Bone Mineral Density after Total Gastrectomy in Males: a Preliminary Report Emphasizing the Possible Significance of Urinary Net Acid Excretion, Serum Gastrin and Phosphorus
Authors: Schmiedl Angelika , Schwille Paul Otto , Stühler Christine , Göhl Jonas , Rümenapf Gerhard 
Published: October 2004

Abstract
The bone mineral density (BMD) and the associated extracellular status of mineral and acid-base metabolism were evaluated in 11 males, 3–18 years after total gastrectomy (GX). In the lumbar spine, but not in the femoral neck, BMD was decreased in seven, normal in three, and falsely high in one individual. Relative to the limits of normalcy, fasting serum levels of gastrin were low, but normal for calcium, phosphorus, parathyroid hormone, calcitonin and vitamin D, while the level of total alkaline phosphatase was elevated; fasting urine pH and calcium were low, while phosphorus and net acid were high. Regression analyses revealed serum gastrin and phosphorus, and urinary net acid as possible predictors of BMD. It was concluded that over the long-term GX evokes low BMD, but not hyperparathyroidism and deranged vitamin D metabolites. Future studies may focus on gastrin, parathyroid hormone-independent hyperphosphaturia and disturbed acid-base metabolism as indicators of a new extra-cellular equilibrium of minerals.
Characterization of the Isoenzyme Profile of β-N-Acetylhexosaminidase in the Urine of Newborns
Authors: Pérez Luis F. , Martínez M. Isabel , Ribeiro Helena M. , Pinto Rui A. , Miranda M. Clara Sá , Tutor J. Carlos 
Published: October 2004

Abstract
The urinary isoenzymes of β-N-acetylhexosaminidase (Hex) in newborn infants were characterised by chromatography, electrophoresis, thermodynamic analysis and through substrate specificity. No qualitative difference was found for the major Hex A and Hex B isoenzymes between full-term or premature newborns and adults, although in the latter group the relative proportion of Hex B is much lower (18.5 ± 2.7 % vs. 36.3 ± 1.0 %). An additional minor enzyme form was found in some premature newborns, which eluted from the DEAE-cellulose column at a higher concentration of NaCl than Hex A and, like this isoenzyme, is able to hydrolyse 4-methylumbellipheryl-2-acetamido-2-deoxy-β-D-glucopyranoside-6-sulphate, which would suggest that it has α subunits in its molecule. These results do not confirm the hypothesis of other authors about the existence of a unique fetal Hex isoenzyme in neonatal urine which eluted before the application of the NaCl gradient, similarly to the Hex B.
Oxidized Low Density Lipoprotein: Atherogenic and Proinflammatory Characteristics during Macrophage Foam Cell Formation. An Inhibitory Role for Nutritional Antioxidants and Serum Paraoxonase
Authors: Kaplan Marielle , Aviram Michael 
Published: October 2004

Abstract
Oxidative stress and inflammatory processes are of major importance in atherogenesis because they stimulate oxidized LDL (Ox-LDL)-induced macrophage cholesterol accumulation and foam cell formation, the hallmark of early atherosclerosis. Under oxidative stress, both blood monocytes and plasma lipoproteins invade the arterial wall, where they are exposed to atherogenic modifications. Oxidative stress stimulates endothelial secretion of monocyte chemoattractant protein 1 (MCP-1) and of macrophage colony stimulating factor (M-CSF), leading to monocyte adhesion and differentiation, respectively. LDL binds to extracellular matrix (ECM secreted by endothelial cells, smooth muscle cells and macrophages) proteoglycans, in a process that contributes to the enhanced susceptibility of the lipoprotein to oxidation by arterial wall macrophages. ECM-retained Ox-LDL is taken up by activated macrophages via their scavenger receptors. This leads to cellular cholesterol accumulation and enhanced atherogenesis. Protection of LDL against oxidation by antioxidants that can act directly on the LDL, or indirectly on the cellular oxidative machinery, or conversion of Ox-LDL to a non-atherogenic particle by HDL-associated paraoxonase (PON-1), can contribute to attenuation of atherosclerosis.
Molecular Aspects and Natural Source of Procalcitonin
Authors: Russwurm Stefan , Wiederhold Matthias , Oberhoffer Mathias , Stonans Ilmars , Zipfel Peter F. , Reinhart Konrad 
Published: October 2004

AbstractThe search for sensitive and specific markers of systemic infection has shown that procalcitonin levels are increased in sepsis, and, consequently, this plasma protein has come into the focus of clinical research. Human procalcitonin is encoded by theCalc-Igene, which gives rise to two alternatively spliced transcripts. Despite systemic investigation of theCalc-Igene and mechanisms of the tissue-specific regulation and alternative splicing, little is known about the biology of procalcitonin and the cells which express this protein during inflammation. Here we focus on the molecular and biochemical properties of the molecule and summarize the known biological functions of procalcitonin. We report on the structure of theCalc-Igene, the amino acid conservation of procalcitonin in different species, and the consensus sequences of the protein with regard to sites relevant for posttranslational modification, spatial distribution, and homologies to other cytokines. We discuss aspects of intracellular location of procalcitonin and demonstrate that it has the characteristics of a secreted protein.
Rat Tissue Collagen Modified by Advanced Glycation: Correlation with Duration of Diabetes and Glycemic Control
Authors: Turk Zdenka , Mišur Irena , Turk Nikša , Benko Bojan 
Published: October 2004

Abstract
Collagenous proteins are especially prone to nonenzymatic glycation, because they contain several dibasic amino acid residues with free amino groups, have a very slow turnover rate, and are exposed to ambient levels of glucose. The aim of this study was to determine the time-dependent course of advanced glycation process in diabetic rats in relation to glycemic control and duration of diabetes, compared to age-matched controls. Immunochemical assay with antibodies to advanced glycation end products (AGE) was first developed to qualitatively detect and quantify the AGE formed in rat tendon and aortic collagen. Individual collagen samples were extracted by extensive pepsin and collagenase digestion. The amount of AGE was measured by competitive ELISA and results were expressed as AGE U/mg collagen. Diabetic rats showed a significant increase in AGE content in aortic collagen at 20 weeks (n=6, 206.6 ± 16.7 U/mg collagen) compared with that measured at 4 and 12 weeks (n=6, 110 ± 12.8 U/mg collagen, and n=13, 184.9 ± 12.3 U/mg collagen at 4 and 12 weeks, respectively; p < 0.001 between 20 weeks and 4 weeks; p < 0.01 between 20 weeks and 12 weeks). The amount of AGE in tendon collagen of diabetic rats increased from 1.9 ± 0.38 U/mg at 4 weeks to 11.2 ± 6.1 U/mg collagen at 20 weeks, p < 0.001. Considerable disparity was observed in the intensity of glycation between aortic and tendon collagen. AGE-content per mg of aortic collagen was several-fold to that found in tendon collagen (p < 0.001). To investigate the effect of glycemic control on the advanced glycation process, total aortic AGE-collagen content was compared between untreated diabetic rats (D; n=13, 184.9 ± 12.3 U/mg) and diabetic rats treated for 12 weeks with insulin (DI; n=6, 133.9 ± 10.7 U/mg), or phlorizin (DP; n=6, 132.4 ± 8.9 U/mg), or by a combination of insulin/phlorizin (DIP; n=6, 124.3 ± 6.5 U/mg). In spite of therapy used, all groups of diabetic animals had a significantly higher aortic AGE-collagen content than those in the nondiabetic control group (C: n=8, 104.6 ± 14.9 U/mg) of the same age (D, DI, DP, DIP vs. C, p < 0.001). Comparison between the mean levels of glycated hemoglobin (D: 5.62 ± 0.38 % vs.C: 1.7 ± 0.05 %) and mean AGE levels in the studied group of animals yielded a very good exponential correlation (r = 0.89, p < 0.001). Glycation-derived late-stage collagen modification was detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and by immunoblotting confirmed to contain (an) AGE-structure(s). Our study provides strong immunochemical evidence of AGE formation in vivo during hyperglycemia, and of their temporal association with structural alterations of extracellular matrix proteins. The advanced glycation process is retarded and reduced in intensity, but not completely abolished, by glycemia regulation with, or independently of, insulin.
Reference Values for a Homogeneous Ferritin Assay and Traceability to the 3rd International Recombinant Standard for Ferritin (NIBSC Code 94/572)
Authors: Lotz Johannes , Hafner Gerd , Prellwitz Winfried 
Published: October 2004

Abstract
Reference values for two ferritin assays (Tina-quant®a Ferritin, Enzymun®, both Roche Diagnostics, Mannheim, Germany) were established (136 males and 139 females). To rule out inflammation as well as iron deficiency in the reference population, subjects with the C-reactive protein concentration < 5 mg/l, and zinc protoporphyrin < 40 µmol/mol heme and the soluble transferrin receptor < 3 mg/l were selected. Taking into account latent iron deficiency as well as hereditary hemochromatosis the 5–95 percentile range was as follows: male, 27–365 μg/l; female, 13–148 μg/l for Tina-quant®a and 12–151 μg/l for Enzymun®. The Tinaquant® a Ferritin assay showed a very good correlation (r≧0.990) to Enzymun® ferritin, Ferritin Abbott® (Abbott Diagnostics, Delkenheim, Germany), N Latex Ferritin® (Dade Behring, Marburg, Germany) and the Ferritin Chiron® (Chiron Diagnostics, Fernwald, Germany). However, the slopes of the standard principal component method analysis were calculated to be between 1.03 (Enzymun®) and 1.41 (N Latex Ferritin®). For four assays the median recovery of the 3rd International Recombinant Ferritin Standard (NIBSC 94/572) measured by serial dilution was 89–109 %. The N Latex Ferritin® assay recovered half of the target values. Because of the good correlation with other assays, a matrix effect is likely. The question arises whether the manufacturers' agreement on the recombinant
Neural Networks for the Biochemical Prediction of Bone Mass Loss
Authors: Queraltó Josep M. , Torres Josep , Guinot Misericordia 
Published: October 2004

AbstractNeural networks are specialized artificial intelligence techniques that have shown high efficiency in dealing with complex problems. Paradigms such as backpropagation have been successfully applied in a number of biomedical applications, but not in attempts to identify women at risk of postmenopausal osteoporotic complications. In this paper, several neural networks were trained using different combinations of biochemical variables as inputs. Bone densitometric measurements in Ward's triangle and in the spinal column were used as separate classification criteria (outputs) between slow and fast bone mass losers. The most parsimonious model with the best performance included plasma concentrations of estrone, estradiol, osteocalcin, parathyrin and urine concentrations of calcium and hydroxyproline (expressed as ratio to creatinine excretion) as input neurons; ten neurons in a single hidden layer; and one neuron in the output layer. Diagnostic efficiency was 76 % in Ward's triangle and 74 % in the spinal column; sensitivity was 70 and 81 %, and specificity was 77 and 65 %, respectively. Linear discriminant analysis showed a diagnostic efficiency of 66 % in Ward's triangle and 64 % in the spinal column, sensitivity was 55 and 86 %, and specificity was 75 and 13 %, respectively. We conclude that performance of the stepwise discriminant analysis was not superior to the neural networks.