bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of CYP2D6*3 and 2D6*4 Allelic Variants by PCR-Restriction Fragment Length Polymorphism
Authors: Topić Elizabeta , Štefanović Mario , Nikolić Vjeran , Zoričić Ivan , Ivanišević Ana-Maria , Žuntar Irena 
Published: October 2004

Abstract
The mutant of CYP2D6*3 allele with A2637 deletion in exon 5 and the mutant of CYP2D6*4 allele G1934→A, splice site defect are among the most common polymorphic alleles of CYP2D6 gene, resulting in a decreased or no activity of CYP isoenzyme. In this study, a reliable polymerase chain reaction-restriction fragment length polymorphism method for identification of CYP2D6*3 and CYP2D6*4 alleles was used to investigate the genotype and phenotype prevalence in the groups of normal controls, and of cirrhosis and cancer patients. The results showed none of 36 controls genotyped for 2D6*3 and 2D6*4 allele to have the 2D6*3 allele with frameshift mutation in exon 5, while 33 % (n=12) were found to bear the 2D6*4 allele with G to A mutation at the intron 3—exon 4 junction. In breast cancer patients (n=35) genotyped for 2D6*3 and 2D6*4 alleles, none with 2D6*3 allele was found either, but 60 % (n=18) were found to bear the 2D6*4 allele. In patients with head and neck squamous cell cancer, there was only one subject with 2D6*3 allele and he was heterozygous. Among them, as many as ten (40 %) patients were found to bear 2D6*4 allele. In the cirrhosis group, none of the patients was found to have the 2D6*3 allele, while the CYP2D6*4 allele was found in 23 % (n=6) patients. The phenotype predicted according to the genotype was as follows: in the control group, 3% of individuals were identified as poor metabolizers, 70 % as extensive metabolizers, and 27 % as heterozygote extensive metabolizers. In the group of breast cancer, 7% of the patients were identified as poor metabolizer, 57 % as extensive metabolizer and 36% as phenotype. In squamous cell cancer and cirrhosis patients, the incidence of poor metabolizer was zero, and of heterozygotes extensive metabolizer 42 % and 31 %, respectively.
Follitropin (FSH) Deficiency in an Infertile Male due to FSHβ Gene Mutation. A Syndrome of Normal Puberty and Virilization but Under-developed Testicles with Azoospermia, Low FSH but High Lutropin and Normal Serum Testosterone Concentrations
Authors: Lindstedt Göran , Nyström Ernst , Matthews Clare , Ernest Ingrid , Janson Per Olof , Chatterjee Krishna 
Published: October 2004

Abstract
We studied a man who sought medical attention at age 28 years because of infertility in both his first and second marriages. His sexual development appeared to have been normal, with normal puberty and virilization, and normal libido and sexual potency. At examination, his testicles were small and soft; otherwise he had a normal physical appearance. Evaluations revealed azoospermia, undetectable in serum before and after 100 μg of intravenously administered gonadotrophin releasing hormone, but moderately elevated lutropin concentration with a brisk rise after gonadotrophin releasing hormone. The α subunit concentration was normal before and after gonadotrophin releasing hormone; that of inhibin B was very low. Analysis of the follitropin β gene, exon 3, revealed a Cys82 → Arg mutation (TGT → CGT). Judging from studies of the biosynthesis of the chorionic gonadotrophin β subunit one may conclude that inability to form the first intramolecular disulphide bond in the follitropin β subunit results in an abnormal tertiary structure during follitropin β biosynthesis with extensive intracellular degradation of the products, inability to associate with the α subunit and defective glycosylation, as well as inability to form a biologically active hormone. This first male case of follitropin deficiency thus defines a new syndrome of male infertility.
Molecular Analysis and Electromyoneurographic Abnormalities in Croatian Children with Proximal Spinal Muscular Atrophies
Authors: Barišić Nina , Sertić Jadranka , Billi Christopher , Barić Ivo , Sarnavka Vladimir , Babić Tomislav , Hrabač Pero , Begović Davor , Florentin Lina , Stavljenić-Rukavina Ana 
Published: October 2004

Abstract
Childhood onset proximal spinal muscular atrophy presents with considerable clinical variability. This study included 14 Croatian children aged 11 days to 8 years with spinal muscular atrophy types I-III verified clinically and electromyoneurographically. DNA of affected children was screened for deletions of exons 7 and 8 of the survival motor neuron gene and for deletion of exon 5 of the neuronal apoptosis inhibitor protein gene. Motor nerve conduction velocity and compound muscle action potential amplitude were decreased in children with spinal muscular atrophy type I and II. Deletions of exons 7 and 8 of the survival motor neuron gene and of exon 5 of the neuronal apoptosis inhibitor protein gene in children with spinal muscular atrophy type I-II suggested existence of more genetic abnormalities as compared to type III.
A decrease in compound muscle action potential amplitude and motor nerve conduction velocity in children with spinal muscular atrophy correlated with the disease severity, probably as a result of axonal degeneration.
Phenotypic severity in children onset spinal muscular atrophy is directly correlated with the extent of survival motor neuron and neuronal apoptosis inhibitor protein exon deletions.
Improved Laboratory Test Selection and Enhanced Perception of Test Results as Tools for Cost-Effective Medicine
Authors: Mayer Michael , Wilkinson Ian , Heikkinen Risto , Ørntoft Torben , Magid Erik 
Published: October 2004

Abstract
Inconsistencies in the way physicians perceive and handle identical laboratory results have untoward effects on morbidity, mortality and cost of medical care. In this context, the selection of suitable tests to answer definite clinical questions, and the manner in which laboratory results are presented have great impact on the action taken by the clinician.
This review addresses preferred methods to improve laboratory test selection, and examines methods that more effectively convey laboratory results to clinicians. It is anticipated that refined selection of tests, and presentation of the test results in a configuration that is easily perceived by the clinician, will facilitate interpretation of laboratory reports. Furthermore, any measures that promote the application of laboratory information in medical practice improve economics at the laboratory-clinical interface.
The presently described methods to optimize test selection and interpretation are:
likelihood ratios to provide estimates of the ability of a test to identify a clinical condition;
consensus-and discriminant function-analysis to estimate the performance of tests in diagnosing a particular disease or condition;
receiver operating characteristic (ROC) curves to assess discrimination capabilities.
The methods which improve test result perception are expression of results as multiples of the upper normal limit, utilizing signal strength to provide prognostic probabilities, and presentation of results in graphic forms that display mutually interrelated functions, with a specific cluster of results being highly suggestive of a given condition.
In addition, we discuss application of expert systems to provide rules based on knowledge and experience to analyze results of tests and suggest diagnosis and action, including additional tests when required.
It is anticipated that judicious utilization of laboratory services by application of the reviewed methodologies will help to achieve medically justified responses at a lower cost and help to achieve a proper balance between cost of tests and their clinical usefulness.
Effect of Haptoglobin Phenotypes on Growth ofStreptococcus pyogenes
Authors: Delanghe Joris , Langlois Michel , Ouyang Jin , Claeys Geert , Buyzere Marc De , Wuyts Birgitte 
Published: October 2004

AbstractThe haptoglobin (Hp) 2–1 and 2–2 phenotypes have been shown to agglutinateStreptococcus pyogenescarrying the membrane antigen T4. In this study, the growth rate of two strains ofStreptococcus pyogenes(T1 and T4) in human serum was compared among haptoglobin phenotypesin vitro. During incubation for 16 hours in serum of different haptoglobin types, only Hp 2–1 and Hp 2–2 sera showed an inhibitory effect on growth, Hp 2–2 being 1.85 times more potent than Hp 2–1. Growth ofStreptococcus pyogenesT4 negatively correlated with the serum concentration of Hp 2–1 (r = −0.908) and Hp 2–2 (r = −0.953). Haptoglobin-depleted serum had no inhibitory effect on bacterial growth. Addition of haemoglobin and ferric citrate to the serum accelerated the growth ofStreptococcus pyogenesT4 (P < 0.05) but not in Hp 2–2 serum. Haptoglobin types 2–1 and 2–2 can be regarded as inhibitors ofStreptococcus pyogenesgrowthin vitro. These data point towards a potential protective role of Hp 2–2 inStreptococcus pyogenesinfectionin vivo, independently of iron uptake.
The Cleavage of Pro-Urokinase Type Plasminogen Activator by Stromelysin-1
Authors: Orgel Dagmar , Schröder Werner , Hecker-Kia Adelheid , Weithmann Klaus Ulrich , Kolkenbrock Hansjörg , Ulbrich Norbert 
Published: October 2004

AbstractMembrane binding of urokinase type plasminogen activator (u-PA) is thought to play a pivotal role in connective tissue remodeling and invasive processes. We compare the ability of different matrix-metalloproteinases involved in connective tissue turnover to cleave pro-urokinase type plasminogen activator between the catalytic domain and the receptor binding part to investigate a potential role for matrix-metalloproteinases in the regulation of membrane-associated proteolytic activity. We employed several forms of human stromelysin-1 (full length, C-truncated, and recombinant catalytic domain), rabbit C-truncated stromelysin-1, the human gelatinases A and B and the human catalytic domain of neutrophil collagenase. The gelatinases and the collagenase did not separate the receptor binding domain of pro-urokinase type plasminogen activator from the catalytic domain, whereas all stromelysin-1 forms cleaved the glutamic acid 143-leucine 144 bond of pro-urokinase type plasminogen activator. This reaction could be inhibited by specific inhibitors of matrix metalloproteinases and was not affected by inhibitors of serine proteinases. TheMr31000 cleavage product with leucine 144 as N-terminus displayed no proteolytic activity towards the prourokinase type plasminogen activator substrate pyro-Glu-Gly-Arg-pNA-HCl (S2444), but it could be activated by an additional treatment with plasmin. Comparison between full length stromelysin-1 and its C-truncated forms, showed that both exhibited the same cleavage properties towards pro-urokinase type plasminogen activator. Thus, the cleavage of pro-urokinase type plasminogen activator by stromelysin-1 is not influenced by the presence or absence of the C-terminal domain. The recombinant catalytic domain of MMP-3 generated pro-urokinase type plasminogen activator, whereas incubation of pro-urokinase type plasminogen activator with the native forms of human or rabbit stromelysin-1 led to a moderate activation of pro-uPA due to an additional cleavage that is catalyzed by a serine proteinase.
Cathepsin B in Human Leukocytes
Authors: Den Tandt Wilfried Richard , Scharpé Simon 
Published: October 2004

Abstract
We have applied a method using the fluorigenic substrate benzoloxycarbonyl-Arg-Arg-amido-4-methylcoumarin to measure cathepsin B, a thiol proteinase, in homogenates of human leukocytes. Data like pH optimum, stability, influence of thiol groups and effects of thiol proteinase inhibitors, lack of binding to Concanavalin A and lack of contribution to the fluorescence by other cathepsins indicate that cathepsin B is the enzyme masured.
Although the activity of the enzyme was linear with respect to time at all protein concentrations measured, there was an acceptable 10% deviation of the enzyme activity from linearity as a function of protein concentration. The enzyme in the homogenate was stable at 0 °C but was rapidly inactivated at 50 °C and above pH 6.5–7. Very limited activation on the one hand and variable inhibition on the other was seen by reagents containing thiol groups and thiol proteinase inhibitors respectively.
Latency (60% of the enzyme activity) indicates a probable subcellular lysosomal localization. There is no affinity towards the lectin Concanavalin A and the Km value was around 1 mmol/l. Normal enzyme activity values in leukocyte homogenates were determined.
Pattern of Plasma Cyclic Nucleotides and Related Hormones in Liver Cirrhosis and Hepatocellular Cacinoma
Authors: Bamonti-Catena Fabrizia , Peracchi Maddalena , Conte Dario , Cantalamessa Luigi , Lorenzano Elettra , Orsatti Alessandra , Salerno Francesco 
Published: October 2004

Abstract
To evaluate the pattern of plasma cyclic adenosine 3′,5‵-monophosphate, cyclic guanosine 3‵,5‵-monophosphate, atrial natriuretic factor and glucagon levels in different stages of chronic liver diseases, we measured these variables in 20 normal subjects, 25 patients with genetic hemochromatosis, associated with liver cirrhosis in 19 cases and not in six, eight patients with compensated and 15 with decompensated alcoholic or posthepatitic cirrhosis, and 12 with hepatocellular carcinoma. All variables were within the normal range in non-cirrhotic hemochromatotic patients. Cyclic adenosine 3‵,5‵-monophosphate levels were within the normal range (9.5–15.7 nmol/l) in hemochromatotic cirrhotics and elevated in other patients. Cyclic guanosine 3‵,5‵-monophosphate, atrial natriuretic factor and glucagon were above the normal ranges (1.92–5.91 nmol/l, 8.8–62.7 ng/l, and 39–165 ng/l, respectively) in most patients with cirrhosis both with and without hemochromatosis and in most individuals with hepatocellular carcinoma. Cyclic guanosine 3‵,5‵-monophosphate correlated with atrial natriuretic factor in the former groups but not in the latter. These findings indicate that glucagon and atrial natriuretic factor hypersecretion is an early event in cirrhosis, regardless of its etiology. In hepatocellular carcinoma, the underlying cirrhosis may account for most hormonal and metabolic changes although cyclic guanosine 3‵,5‵-monophosphate increases could also be due to the neoplastic process per se.
Serum Ionized versus Total Magnesium in Patients with Intestinal or Liver Disease
Authors: Saha Heikki , Harmoinen Aimo , Karvonen Anna-Liisa , Mustonen Jukka , Pasternack Amos 
Published: October 2004

Abstract
In serum, magnesium exists in three fractions: protein-bound, complex-bound and free ionized form. Only the free ionized fraction is biologically active. Until recently, only the measurement of serum total magnesium has been in clinical use. Now, commercially available instruments using new ion-selective electrodes for Mg++ have made possible the reliable measurement of serum ionized magnesium in clinical practice. For the measurement of serum ionized magnesium we used a magnesium-selective electrode installed in a six-channel electrolyte analyzer. We compared the use of ionized versus total magnesium measurement in 52 patients with intestinal disease, 54 with liver disease, and in 75 healthy control subjects.
In the patients with alcoholic liver disease both serum ionized and total magnesium were lower, and in those with inflammatory bowel disease slightly higher than in control subjects. The correlation coefficient between serum ionized and total magnesium was r=0.87 (p<0.001) in the patients, and r=0.75 (p<0.001) in the controls. In the patient group the fraction of ionized magnesium in the total was negatively related to the serum albumin level (r=−0.41, p<0.001). Serum total magnesium was below the reference range in 30 out of 150 measurements, serum ionized magnesium in only 9 out of 150 measurements, respectively. Thus, 21 cases with low total but normal ionized magnesium (two thirds of hypomagnesemia according to serum total magnesium) were false positive. Total magnesium measurement may overestimate the incidence of hypomagnesemia when significant hypoalbuminemia is present. Measurement of serum ionized magnesium instead of total magnesium may therefore be of advantage in evaluating patients with hypoalbuminemia and when hypomagnesemia is expected.
Evaluation of the Analytical Performances of a New Fully Automated Commercial Immunonephelometric Assay for Lipoprotein(a)
Authors: Lippi Giuseppe , Ruzzenente Orazio , Brentegani Claudio , Pierotti Anna , Guidi Giancesare 
Published: October 2004

Abstract
Several commercial methods have been proposed for lipoprotein(a) (Lp(a)) measurements over the past decades. However, only a few of them appear completely suitable in terms of analytical performance, costs and practicability. We evaluated the analytical performance of a new commercial fully automated immunonephelometric assay for Lp(a) measurements on the IMMAGE® Immunochemistry System. Mean within- and between-run coefficients of variation were 2.7 % (range 1.2–4.7 %) and 3.8 % (range 1.8–7.9 %), respectively. The linearity of the assay was confirmed up to 102 mg/dl and the deviation from the expected values did not exceed 4% (mean deviation: 1.9%). Moreover, the relative non-linearity was acceptable, ranging from 1.4 % to 1.6 % and hence constantly lower than the 2.5 % upper limit. Since there is no reference method for Lp(a) measurements, 100 routine random serum samples measured by the IMMAGE® Immunochemistry System immunonephelometric assay were further compared with two other commercial immunonephelometric assays (Array® LPA immunonephelometric assay and BNA Latex-Enhanced Lp(a) nephelometric assay). Non-parametric regression and relative Spearman's correlation coefficients were satisfactory, (y = 1.009x−1.38; r = 0.998 IMMAGE® Immunochemistry System vs. Array LPA and y = 0.922x−0.40; r = 0.989 IMMAGE® Immunochemistry System vs. Behring Nephelometer Analyzer (BNA) Latex Lp(a) assay). On the basis of the results of the present evaluation we conclude that the analytical performance and the main technical features of the IMMAGE® Immunochemistry System immunonephelometric assay make it a suitable method for Lp(a) measurement in clinical laboratories.
Immunoradiometric Assay of Thyroglobulin in Patients with Differentiated Thyroid Carcinomas: Need for Thyroglobulin Recovery Tests
Authors: Bourrel François , Hoff Madeleine , Regis Henri , Courrière Philippe , Caron Philippe 
Published: October 2004

Abstract
As interference from thyroglobulin autoantibodies appears to have been overcome in new commercial thyroglobulin assays by the use of monoclonal antibodies, the need for thyroglobulin recovery tests became uncertain. Sera (n=45) from patients with differentiated thyroid carcinomas were selected on the basis of a thyroglobulin recovery value below 70 % in the Dynotest Tg immunoradiometric assay (Brahms) routinely used in our laboratory. Serum thyroglobulin levels were then measured using three other commercial immunoradiometric assays: thyroglobulin ERIA (Pasteur), HTGK (Sorin) and ELSA HTG (Cis Bio International). Thyroglobulin autoantibodies were measured using the Thyrak assay (Brahms). Although many patients were thyroglobulin antibodies-negative (< 200 U/ml, n=26), most immunoradiometric assays failed to detect thyroglobulin in patients with evidence of recurrence. Low thyroglobulin values associated with low thyroglobulin recovery in thyroglobulin antibodynegative patients appear to be more biologically relevant than a single low thyroglobulin value, which can lead to lack of medical intervention. We conclude that the thyroglobulin recovery test is a prerequisite for the correct interpretation of serum thyroglobulin levels determined with immunoradiometric assays in the follow-up of thyroglobulin autoantibody-negative patients treated for differentiated thyroid carcinomas.
Effect of Thyroid Hormones on Lp(a) and Lipid Metabolism
Authors: Engler Hanna , Riesen Walter F. 
Published: October 2004

Abstract
The effect of thyroid hormones on lipoprotein(a) plasma concentrations and the other parameters of lipoprotein metabolism was studied in 158 patients with thyroid dysfunction and in 37 euthyroid controls (cross-sectional study). Multiple regression analysis revealed that 65.5 % of the variability in lipoprotein(a) levels were predicted by changes in lipoprotein(a) phenotypes (60.5 %), thyrotropin (3.5 %), and age (0.8 %). The lipid parameters, however, showed no significant effect on lipoprotein(a). A subgroup analysis on samples from patients with large lipoprotein(a) isoforms showed that 28% of the variability in lipoprotein(a) concentrations could be explained by changes in thyroid function (19.1 %), age (6.5 %) and triglycerides (3.5 %). Much stronger correlations were found between thyrotropin and total cholesterol, low density lipoprotein cholesterol or apolipoprotein B respectively (R2=0.951 for low density lipoprotein cholesterol, R2=0.801 for apolipoprotein B). Our data suggest that thyroid hormone is a significant modulator of lipoprotein(a) metabolism. However, different mechanisms are responsible for the change in lipoprotein(a) levels and for the decrease in total-and low density lipoprotein cholesterol levels.
Evaluation of the First Automated Thyroglobulin Assay
Authors: Vogeser Michael , Knesewitsch Peter , Jacob Karl , Seidel Dietrich 
Published: October 2004

Abstract
The aim of this study was to investigate technical and analytical performance of the first automated thyroglobulin (Tg) assay (DPC-Immulite®; Diagnostic Products Corporation, Los Angeles, USA). In imprecision studies using several human serum pools ranging from 21 to 58 replicates, a coefficient of variation of 9.0 % was obtained at a mean Tg concentration of 0.84 ng/ml and of 6.1 % at a Tg concentration of 62.1 ng/ml. In a method comparison with a non-automated assay (BRAHMS LUMItest Tg®, BRAHMS, Berlin, Germany) using 383 sera of 303 patients with thyroid carcinoma, regression analysis according to Passing and Bablock yielded in the following equation:
Immulite Tg=1.6 × BRAHMS Tg−0.1 ng/ml
(Pearson's r=0.979).
Sera obtained from 59 patients with thyroid carcinoma enabled comparative follow-up studies; in all cases qualitative agreement was found with regard to increase or decrease of serum Tg; in eight cases, however, Tg was detected with the Immulite assay but not with the BRAHMS assay. Further follow-up proved the presence of thyroid tissue in these patients. From these and further methodological data (dilution linearity, interference studies, carry-over study, high-dose hook properties, and short report time) it is concluded that the DPC-Immulite Tg assay meets the requirements of routine diagnostic use.
Lactoferrin: A Multifunctional Glycoprotein Involved in the Modulation of the Inflammatory Process
Authors: Baveye Sophie , Elass Elisabeth , Mazurier Joël , Spik Geneviève , Legrand Dominique 
Published: October 2004

AbstractLactoferrin is an iron-binding glycoprotein found in exocrine secretions of mammals and released from neutrophilic granules during inflammation. This review describes the biological roles of lactoferrin in host defence. Secreted lactoferrin exerts antimicrobial action either by chelation of iron or by destabilization of bacterial membranes. Furthermore, lactoferrin modulates the inflammatory process, mainly by preventing the release of cytokines from monocytes and by regulating the proliferation and differentiation of immune cells. Some of these activities are related to the ability of lactoferrin to bind lipopolysaccharides (LPS) with high affinity. Indeed, recentin vitrostudies indicate that lactoferrin is able to compete with the LPS-binding protein for LPS binding and therefore to prevent the transfer of LPS to CD14 present at the surface of monocytes. Moreover, the prophylactic properties of lactoferrin against septicemiain vivohave been demonstrated. Taken as a whole, these observations strongly suggest that lactoferrin is one of the key molecules which modulate the inflammatory response.