bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apolipoprotein E polymorphism and serum lipid response to plant sterols in humans
Authors: Geelen A. , Zock P. L. , De Vries J. H. M. , Katan M. B. 
Published: March 2003

AbstractBackground The apolipoprotein E polymorphism may influence the absorption of cholesterol from the intestine and thus the response of serum cholesterol to diet. We decided to use plant sterols to investigate this and studied whether the cholesterol‐lowering effect of plant sterols differed between subjects with different apolipoprotein E genotyes.Design Thirty‐one healthy subjects with the E3/4 or E4/4 genotype and 57 with the E3/3 genotype were fed sterol‐enriched margarine or control margarine for 3 weeks each in a blind randomised cross‐over design. The sterol margarine provided 3·2 g of plant sterols daily, was low‐fat, and had the same fatty acid composition as the control margarine. Subjects used the margarines as part of their usual diet, which was fairly low in cholesterol (mean, 175 mg per day). The mean (± standard deviation) age of the subjects was 25 (± 11) years.Results The apolipoprotein E polymorphism did not significantly affect the responses of total and LDL cholesterol. The decrease in total cholesterol was 0·36 mmol L−1 (7·4%) in the E3/3 subjects and 0·31 mmol L−1 (5·7%) in the ɛ4 subjects (P = 0·50) and that in LDL cholesterol was 0·34 mmol L−1 (12·2%) in the E3/3 subjects and 0·32 mmol L−1 (9·8%) in the ɛ4 subjects (P = 0·68).Conclusion The serum cholesterol response to plant sterols is not affected by the apolipoprotein E polymorphism in healthy subjects who consume a low‐cholesterol diet.
Prior aspirin use in unstable angina patients with modified plasma inflammatory markers and endothelial nitric oxide synthase in neutrophils
Authors: Mateos‐Cáreres P. J. , García‐Méndez A. , Farré J. , Sánchez de Miguel L. , Gómez J. , De Andres R. , Rico L. , Romero J. , López‐Farré A. 
Published: March 2003

AbstractBackground  Prior use of aspirin in patients with acute coronary syndrome has been associated with a lower incidence of acute myocardial infarction. The aim of this study was to explore if prior aspirin therapy in unstable angina (UA) patients could modify systemic inflammatory markers such as interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α) and intercellular adhesion molecule‐1 (ICAM‐1) and the expression of endothelial nitric oxide synthase (eNOS) in neutrophils.Materials and methods Unstable angina was defined as transient S‐T segment changes without significant increases in CK and CK‐MB. We studied 50 consecutive patients admitted to hospital within 24 h after the onset of chest pain. The number of patients with prior aspirin was significantly higher (n = 32) than those not taking aspirin (n = 18) on admission.Results Plasma levels of IL‐6 and ICAM‐1 were significantly increased in the UA patients when compared with the healthy control volunteers (n = 20) used as a reference for normal values. Plasma levels of both IL‐6 and ICAM‐1 were reduced in patients taking aspirin. There were no differences in the plasma levels of TNF‐α between the UA patients and the control volunteers. The eNOS protein expression was also higher in neutrophils from the UA patients taking aspirin than in those not taking aspirin.Conclusion Patients taking aspirin before UA showed a lower systemic inflammatory response and higher eNOS protein expression in their neutrophils
Effects of iloprost on adhesion molecules and F1 + 2 in peripheral ischemia
Authors: Mazzone A. , Faggioli P. , Cusa C. , Stefanin C. , Rondena M. , Morelli B. 
Published: March 2003

AbstractBackground Iloprost has beneficial effects on microcirculation by preventing platelet and leukocyte reciprocal activation, which is known to lead to endothelial damage and acute thrombosis. This drug also reduces inflammatory system activation by decreasing αΜβ2 integrin expression on the phagocyte membrane, might have a role in the protection and restoration of endothelial integrity and might interact with coagulation cascade activation.Design Forty patients were enrolled: 29 with systemic sclerosis (SSc) and 11 with peripheral artery disease (PAD). Iloprost was administered for 5 days in the first group and for 21 days in second group of patients. To ascertain whether iloprost modifies the parameters of endothelial and coagulation cascade activations, the plasma concentrations of S‐ICAM‐1 and F1 + 2 were detected in patients at baseline, after 5 days and, in PAD patients only, after 21 days of iloprost therapy. S‐ICAM‐1 is the endothelial counter receptor for αΜβ2 integrin and is a marker of endothelial cell activation; and F1 + 2 is a marker of coagulation cascade activation.Results After infusion of iloprost a significant decrease of S‐ICAM‐1 was observed in both the SSc (P < 0·002) and PAD patients (P < 0·004). Similarly, a significant decrease of F1 + 2 was observed in the SSc (P < 0·0004) and PAD patients (P < 0·003).Conclusions The study provides evidence that iloprost reduces endothelial cells and coagulation cascade activations. Both of these mechanisms are responsible for improvement in microvascular functional capacity and for the long‐term clinical benefit observed. After iloprost infusion, the SSc patients showed marked reductions in F1 + 2 and S‐ICAM‐1 concentrations that were statistically more significant relative to the PAD patients.
Labile iron in parenteral iron formulations and its potential for generating plasma nontransferrin‐bound iron in dialysis patients
Authors: Espósito B. P. , Breuer W. , Slotki I. , Cabantchik Z. I. 
Published: March 2003

AbstractBackground Labile plasma iron (LPI) associated with iron supplementation has been implicated in complications found in dialysis patients. As LPI can potentially catalyse oxygen radical generation, we determined the presence of labile iron in the parenteral preparations and the frequency of occurrence of LPI in dialysis patients.Design The capacity to donate iron to apotransferrin (apo‐) or to the chelator desferrioxamine (DFO) was measured with fluorescein‐Tf (Fl‐Tf) and Fl‐DFO, respectively. Those probes undergo quenching upon binding to iron. Iron‐catalysed generation of oxidant species was determined with dihydrorhodamine. Plasma nontransferrin‐bound iron (NTBI), here termed LPI, was determined by mobilization of iron from low‐affinity binding sites with oxalate, followed by its quantification with Fl‐Tf in the presence of Ga(III).Results Normal individuals and most (80%) dialysis patients, analysed at least 1 week after iron supplementation showed no detectable (<0·2 µm) LPI. However, ≈20% of the patients (n = 71) showed significant LPI levels (>0·2 µm), in some cases weeks after iron administration. LPI levels correlated best (r2 = 0·9) with Tf saturation. The iron preparations contained 2–6% low molecular weight and redox‐active iron, most of which is chelated by Tf.Conclusions Parenteral iron formulations contain a small but significant fraction of redox‐active iron, most of which is scavenged by apo‐Tf within <1 h. Therefore, oxidant stress associated with iron infusion is likely to be transient. The bulk of the polymeric iron is apparently inaccessible to apo‐Tf. Although LPI might return to normal within 2 h of intravenous iron infusion, the long‐term persistence of low‐level LPI in up to 20% of end stage renal disease (ESRD) patients indicates that complete clearance of the intravenous iron may be more protracted than originally estimated.
In vitro and in vivo lipolysis of plasma triglycerides increases the resistance to oxidative modification of low‐density lipoproteins
Authors: Skoglund‐Andersson C. , Karpe F. , Hellénius M.‐L. , Regnström J. , Hamsten A. , Tornvall P. 
Published: March 2003

AbstractBackground The majority of studies on low‐density lipoprotein (LDL) particle size and susceptibility to oxidative modification have been either descriptive or interventional, but there are few mechanistic studies.Materials and methods Effects of exhaustive in vitro and in vivo lipolysis of serum and plasma triglycerides, respectively, by lipoprotein lipase (LPL) were investigated in healthy normotriglyceridemic men. The LDL end‐product of lipolysis of very low‐density lipoprotein (VLDL) underwent compositional analysis, gradient gel electrophoresis and an assessment of resistance to copper‐induced oxidative modification.Results The LDL particle contents of free fatty acid and α‐tocopherol increased, whereas the contents of free and esterified cholesterol, α‐carotene and coenzyme Q10 decreased upon incubation of serum with LPL in vitro. The LDL particle size decreased and the resistance to the oxidative modification of LDL increased. Lipolysis of plasma triglycerides in vivo, achieved by intravenous injection of heparin, did not alter the LDL particle size but increased the resistance to the oxidative modification of LDL. This change was accompanied by an increase in the LDL particle content of α‐tocopherol, whereas the free fatty acid content was unaltered.Conclusions The results show that the increased resistance to oxidative modification of LDL after lipolysis of plasma triglycerides was concomitant with an increased LDL particle content of α‐tocopherol, and that free fatty acids did not seem to contribute to the increased resistance to oxidative modification of LDL in vivo. Furthermore, our data indicate that the resistance of LDL to oxidative modification is not dependent on particle size.
Treatment with atorvastatin alters interleukin‐12 and ‐10 gene expression
Authors: Naoumova R. P. , Patel D. D. , O'Neill F. H. , Thompson G. R. , Knight B. L. 
Published: March 2003

AbstractBackground Statins have been shown to have pleiotropic effects extending beyond their ability to lower cholesterol.Material and methods Seventeen patients with heterozygous familial hypercholesterolaemia participated in a single‐blind placebo controlled study. The patients underwent three treatment regimens: placebo (4 weeks), atorvastatin 10 mg day−1 (4 weeks) and atorvastatin 40 mg day−1 (12 weeks). Following each treatment period, serum lipids and plasma mevalonic acid were measured, mononuclear leukocytes were isolated and total RNA was prepared. The content of mRNA for IL‐12p35 and IL‐10 was assayed, blinded, by real‐time quantitative polymerase chain reactions.Results Treatment of the subjects with atorvastatin decreased the abundance of IL‐12p35 mRNA in mononuclear cells, but did not alter that of IL‐10, so that the ratio of the IL‐12p35 to IL‐10 mRNA content was significantly reduced (P < 0·0026). The IL‐12p35/IL‐10 ratio correlated significantly with plasma mevalonic acid concentrations but not with serum LDL concentrations.Conclusions This study provides evidence that atorvastatin exerts an immunomodulatory effect in vivo, characterized by a decrease in the ratio of IL‐12 mRNA to IL‐10 mRNA in leukocytes. The immunomodulatory effect of statins, in addition to their cholesterol‐lowering properties, may contribute to the rapid cardiovascular benefit observed during treatment with statins and reduced the rate of rejection in patients with solid organ transplantation.
Anti‐cardiolipin antibodies in patients with chronic viral hepatitis are independent of beta2‐glycoprotein I cofactor or features of antiphospholipid syndrome
Authors: Zachou K. , Liaskos C. , Christodoulou D. K. , Kardasi M. , Papadamou G. , Gatselis N. , Georgiadou S. P. , Tsianos E. V. , Dalekos G. N. 
Published: March 2003

AbstractBackground Although controversial, some authorities have implicated hepatitis C virus (HCV) as a cause of anti‐phospholipid syndrome (APLS). Anti‐cardiolipin antibodies (anti‐CLAbs) in APLS are cofactor‐dependent (‘pathogenic’ antibodies). We conducted a study in order to determine the prevalence of anti‐CLAbs in HCV patients, and furthermore to address whether these autoantibodies are cofactor‐dependent or not and whether they are associated with features of APLS. Patients with hepatitis B virus (HBV) were also evaluated in order to assess whether there are differences in the prevalence and the clinical significance of anti‐CLAbs between these two major types of chronic viral hepatitis.Materials and methods One hundred and seventy‐four consecutive HCV patients, 50 HBV patients and 267 healthy were investigated for the presence of anti‐CLAbs and antibodies against beta2‐glycoprotein I (β2‐GPI), which is the most important cofactor of the ‘pathogenic’ anti‐CLAbs in APLS. IgG anti‐CLAbs were determined by an in‐house quantitative ELISA and anti‐β2‐GPIAbs using a commercial ELISA kit.Results 21·3% of the HCV and 14% of the HBV patients tested positive for IgG anti‐CLAbs (P < 0·0001 compared with healthy controls). Neither age, sex, certain epidemiologic and laboratory parameters nor the clinical status and the histologic findings were associated with anti‐CLAbs detection in both diseases. 2·3% of the HCV (P < 0·05 compared with healthy controls) and 2% of the HBV patients tested positive for anti‐β2‐GPIAbs. Presence of anti‐CLAbs was not associated with features of APLS.Conclusions A significant proportion of the HCV and HBV patients had detectable IgG anti‐CLAbs. However, the anti‐CLAbs titres were relatively low, and in most cases seem to be cofactor‐independent (‘nonpathogenic’). The latter is further supported by the lack of their association with clinical features of APLS. Furthermore, anti‐CLAbs appear to be detected irrespective of the demographic, laboratory, clinical and histologic status in both HCV and HBV. However, prospective studies of longer duration may be required in order to address whether anti‐CLAbs in patients with chronic viral hepatitis are or are not of clinical importance.
Polymorphism of DR52‐associated haplotypes in a Croatian population
Authors: Grubic Z. , Z unec R. , Kas telan A. 
Published: March 2003

AbstractWe investigated DR52 haplotype polymorphism in a population of 78 Croatian families with at least one parent and one offspring positive for a DR52‐associated allele, using the PCR–SSOP method. The haplotypes DRB1*0301‐DQA1*0501‐DQB1*0201, DRB1*11‐DQA1*0501‐DQB1*0301 and DRB1*1201‐DQA1*0501‐DQB1*0301 seem to be conserved haplotypes in this Croatian population, while DRB1*13 haplotypes showed high diversity. Among 10 different DRB1*13 haplotypes, four consist of common alleles, while six have an unusual combination of DRB1‐DQA1‐DQB1 alleles. Three haplotypes (DRB1*1301‐DQA1*0103‐DQB1*0503, DRB1*1302‐DQA1*0102‐DQB1*0502 and DRB1*1303‐DQA1*0102‐*DQB1*0502) have not been reported. These results on DR52‐associated haplotype polymorphisms in a Croatian population must be taken into consideration in organ transplantation, especially when searching for unrelated bone marrow donors.
Analysis of the genetic variability of the 1st (CCC/ACC, P52T) and the 10th exons (bp 1012–1704) of the TSH receptor gene in Graves’ disease
Authors: Kaczur Viktória , Takács Mária , Szalai Csaba , Falus András , Nagy Zsuzsa , Berencsi György , Balázs Csaba 
Published: March 2003

AbstractWe determined the genetic variability of the 1st (CCC/ACC, P52T polymorphic variant) and 10th exons (bp 1012–1704) of the TSH receptor (TSHR) gene in Graves’ disease. A total of 101 Graves’ patients and 163 control subjects were screened. The A253 mutant allele was carried by nine patients with Graves’ disease (8.91%) and 13 control subjects (7.98%) in heterozygous genotype. No significant difference in the frequency of the mutant allele was found between Graves’ patients and control subjects. These results provide evidence that the A253 polymorphism has no genetic relevance in Graves’ disease. Moreover, the DNA nucleotide sequence of 693 bp of the 10th exon (bp 1012–1704) of the TSHR gene was determined in 15 Graves’ patients. Six patients were homozygous for the wild‐type allele and nine were heterozygous for the mutant allele at the 253rd nucleotide of the first exon. No polymorphism was found in the DNA sequences obtained from leukocytes of Graves’ patients, similarly to the sequences obtained from the nine control subjects. None of the nine patients carrying the A253 polymorphism in the 1st exon of the TSHR had polymorphism in the examined part of the 10th exon, including two additional patients whose thyroid tissue was directly analysed. In all likelihood, the polymorphisms of the examined regions of either the 1st or the 10th exon of the THSR gene do not contribute to the genetic susceptibility to Graves’ disease.
Molecular cloning of a truncated p62Dok1 isoform, p22Dokdel
Authors: Hubert P. , Ferreira V. , Debre P. , Bismuth G. 
Published: March 2003

AbstractThe p21Ras GTPase activating protein‐associated 62‐kDa protein, p62Dok1, is an early substrate of various tyrosine phosphorylation pathways. Its recent cloning in human myeloid cells and in murine pre‐B cells revealed an N‐terminal pleckstrin‐homology domain and a tyrosine‐ and proline‐rich C‐terminal tail in its sequence. Here, we characterized a new 1261‐bp cDNA identical to that of p62Dok1, but with a central 185‐bp deletion (bp 456–640). This induced a frameshift leading to a premature stop codon. The deduced protein, designated p22Dokdel, corresponded to a truncated p62Dok1 isoform of 177 amino acids that can be expressed both in vitro and in vivo with an apparent molecular mass of 22 kDa. This newly identified molecule was composed of the N‐terminal PH domain of p62Dok1 followed by a new 25‐amino acid C‐terminal sequence containing a typical class II proline‐rich motif, suggesting a specific role for p22Dokdel in signal transduction pathways.
Genetic analysis of the interleukin‐1 receptor antagonist and its homologue IL‐1L1 in alopecia areata: strong severity association and possible gene interaction‡
Authors: Tazi‐Ahnini R. , Cox A. , McDonagh A. J. G. , Nicklin M. J. H. , Di Giovine F. S. , Timms J. M. , Messenger A. G. , Dimitropoulou P. , Duff G. W. , Cork M. J. 
Published: March 2003

SummaryAlopecia areata is an inflammatory hair loss disease with a major genetic component. The presence of focal inflammatory lesions with perifollicular T‐cell infiltrates reflects the importance of local cytokine production in the pathogenesis. In addition to its fundamental pro‐inflammatory role, the interleukin‐1 (IL‐1) system has major effects on hair growth regulation in vitro, with the inhibitory actions of IL‐1α and IL‐1β being opposed by the receptor antagonist IL‐1ra. The novel interleukin‐1 like molecule 1 (IL‐1L1) which has greatest gene sequence homology with IL1RN, the gene encoding IL‐1ra, is another potential IL‐1 antagonist. In view of previous studies suggesting a significant role for IL1RN polymorphisms in the pathogenesis of autoimmune/inflammatory disease, we have analysed polymorphisms of IL‐1ra (IL1RN+2018) and its homologue IL‐1L1 (IL1L1+4734) in a case–control association study on 165 patients and a large number of matched controls. Homozygosity for the rare allele of IL1RN (IL1RN*2) was significantly associated with alopecia areata [odds ratio (OR) = 1.89, 95% CI (1.09, 3.28); P = 0.02], confirming our previous findings of significant association with the IL1RN variable number tandem repeat (VNTR). The results also revealed a novel association involving a polymorphism of the interleukin‐1 receptor antagonist homologue IL1L1 at position + 4734, IL1RN+2018, and alopecia areata. The effect of a genotype combining three copies of the rare alleles at the IL1RN and IL1L1 loci conferred a more than additive increase in the risk of disease compared to IL1RN+2018 or IL1L1+4734 alone [OR 3.37 (1.60, 7.06); P = 0.002], suggesting possible synergy between the IL1RN and IL1L1 genes. This effect was stronger in patients with severe disease (alopecia totalis/universalis) [OR 4.62 (1.87, 11.40), P = 0.0022], and in those with early age at onset (< 20 years) [OR = 6.38 (2.64, 15.42), P = 0.0002]. Our results suggest that these polymorphisms within IL1RN and IL1L1 themselves or a gene in linkage disequilibrium with IL1RN and IL1L1 predispose to the more severe forms of alopecia areata.
CD80 (B7‐1) and CD86 (B7‐2) genes and genetic susceptibility to coeliac disease
Authors: Woolley N. , Holopainen P. , Bourgain C. , Mustalahti K. , Collin P. , Mäki M. , Partanen J. 
Published: March 2003

SummaryThe role of the costimulatory molecules B7‐1 (CD80) and B7‐2 (CD86) in T‐cell activation makes them good candidates for coeliac disease susceptibility genes. We conducted a genetic linkage study of the CD80/86 gene region in the general Finnish population and in a local subisolate. No linkage was found in either population.
Effect of flow rate on the adsorption and desorption of glyphosate, simazine and atrazine in columns of sandy soils
Authors: Beltran J. , Gerritse R. G. , Hernandez F. 
Published: March 2003

SummaryAdsorption and desorption of the herbicides glyphosate [N‐phosphonomethyl‐aminoaceticacid], simazine [6‐chloro‐N,N′‐diethyl‐1,3,5‐triazine‐2,4‐diamine] and atrazine [6‐chloro‐N2‐ethyl‐N4‐isopropyl‐1,3,5‐triazine‐2,4‐diamine] were studied in four sandy soils from Western Australia. Distribution coefficients (Kds) were calculated from breakthrough curves (BTCs) resulting from leaching step changes in concentrations through small saturated columns of soil at flow rates ranging from 0.3 to 30 m day–1. A comparison was made with Kds obtained after batch equilibrating solutions of the herbicides with the same soils. The Kds of herbicides in soils decreased with increasing flow rate and most strongly for glyphosate in soils rich in clay content. Resulting increases in mobility of about 40–50% were estimated for simazine and atrazine and > 50% for glyphosate at flow rates of 3 m day–1. Adsorption and desorption rates were estimated by fitting numerically simulated BTCs to experimental BTCs. Best fits were obtained with a time‐dependent Freundlich adsorption equation. The resulting coefficient for time dependency in the equation suggests that the rates of adsorption and desorption are controlled mainly by diffusion in an adsorbing layer on or in soil particles.
Estimating critical state soil mechanics parameters from shear box tests
Authors: KIRBY J. M. 
Published: March 2003

SummaryPrediction of compaction, tillage, root growth or other soil deformation events requires a description of the stress–strain properties of the soil such as the critical state model, but estimating the parameters is time consuming and expensive. I have developed a method of estimating critical state properties from a single shear box test, both saving much labour and providing more information than traditional analyses. The method is based on critical state analyses of the constant stress and constant volume shear box tests using the total stresses applied at the boundary. It derives the critical state property parameters from test data by minimizing the difference between test data and the simulated soil deformation (and hence the properties used in that simulation). The minimization is a form of regression analysis. The analyses resulted in good simulations of the history of states in space defined by τxyγxy and e space (constant stress test) or τxyγxy and σy space (constant volume test).For normally consolidated samples, the analysis of a single constant stress test provided estimates of the slope of the critical state line (M), the slope of the virgin compression line (λ), the slope of the rebound line (K), and the elastic modulus (E). The standard deviation of the estimate of kcould not be found. By contrast, the analysis of the constant volume test resulted in poor estimates, particularly of λ. This is because the test yields no information on changes of volume during deformation: hence volume change parameters are not successfully estimated. The constant volume test is therefore not suitable for back analysis.