bluuebunny/crossref_metadata_2025 huggingface dataset:
Allelic polymorphism −491A/T in apo E gene modulates the lipid‐lowering response in combined hyperlipidemia treatment
Authors: García‐Otín A.‐L. , Civeira F. , Aristegui R. , Díaz C. , Recalde D. , Sol J. M. , Masramon X. , Hernández G. , Pocoví M. ,   the ATOMIX Study Group
Published: March 2003

Background Combined hyperlipidemia (CHL) is one of the dyslipidemias more frequently found in clinical practice, and lipid‐lowering drugs are often necessary in its management. Some genetic loci have been associated with CHL expression, and some studies have shown modulation of drugs efficiency in the treatment of dyslipidemias by genetic polymorphisms. We have investigated whether common polymorphisms and mutations in the apolipoprotein (apo) E, lipoprotein lipase (LPL), and apo CIII genes influence atorvastatin or bezafibrate responses in patients with CHL.

Design One hundred and sixteen subjects participating in the ATOMIX study (Atorvastatin in Mixed dyslipidemia) were randomized to treatment with either atorvastatin or bezafibrate. Apolipoprotein E genotype and common −491A/T and −219T/G polymorphisms in the apo E gene promoter region, Sst I polymorphism in the apo CIII gene (3238C/G), and D9N and N291S common mutations in the LPL gene were determined by polymerase chain reaction (PCR) and restriction enzyme digestion.

Results Statistical analysis showed the influence of the −491A/T polymorphism in atorvastatin and bezafibrate treatments. Subjects carrying the −491T allele showed an increased LDL‐cholesterol‐lowering effect with atorvastatin compared with −491T allele noncarriers (−35% vs. −27%, P = 0·037). Subjects carrying the −491T allele, when on bezafibrate treatment, showed a lower triglyceride reduction compared with −491T allele noncarriers (−23% vs. −39%, P = 0·05).

Conclusions In our study, the −491A/T polymorphism in the apo E gene promoter region modulated the lipid‐lowering efficiency of atorvastatin and bezafibrate in CHL patients. Such influence might explain some of the interindividual response variabilities observed for the two drugs, and could help in CHL management.
Sodium bicarbonate treatment and ubiquitin gene expression in acidotic human subjects with chronic renal failure
Authors: Roberts R. G. , Redfern C. P. F. , Graham K. A. , Bartlett K. , Wilkinson R. , Goodship T. H. J.
Published: March 2003

Background In chronic renal failure, metabolic acidosis is associated with increased whole body protein degradation. In rats this effect of acidosis occurs in skeletal muscle and is associated with increased ubiquitin mRNA expression. This has not been demonstrated in humans.

Materials and methods Six patients with chronic renal failure and acidosis underwent muscle biopsy before and after 1 month's treatment with sodium bicarbonate. RNA was extracted from the biopsy, and the expression of the genes for ubiquitin and the proteasome component, C2, were measured by Northern blotting.

Results and conclusions There was no significant difference in the expression of ubiquitin or C2 after bicarbonate treatment. This is contrast with results from animal models of acidosis and some other catabolic conditions in humans. This may reflect the complexity of the ubiquitin‐dependent pathway, and it may be that changes in ubiquitin expression are only seen with more severe and/or acute changes in pH.
The relation between Helicobacter pylori and atherosclerosis cannot be explained by a high homocysteine concentration
Authors: Bloemenkamp D. G. M. , Mali W. P. Th. M. , Tanis B. C. , Rosendaal F. R. , Van Den Bosch M. A. A. J. , Kemmeren J. M. , Algra A. , Visseren F. L. J. , Van Der Graaf Y.
Published: March 2003

Background Recent studies have suggested that a chronic infection with Helicobacter pylori might be an independent risk factor for atherosclerosis. However, a direct role in atherogenesis is not plausible, since the bacterium has not been isolated from atherosclerotic lesions. An indirect mechanism that could link H. pylori with atherosclerosis might be through an increase in plasma homocysteine concentration caused by deficiencies of vitamin B12 and folate in plasma.

Materials and methods  In 150 female patients with peripheral arterial disease (PAD) and in 412 healthy control women from a nation‐wide population‐based case–control study, blood samples were collected to determine the antibody titre against H. pylori and to measure plasma homocysteine, folate and vitamin B12 levels. First, the odds ratio for PAD in women with a positive antibody titre against H. pylori was calculated and adjusted for homocysteine level. Secondly, mean concentrations of vitamin B12, folate and homocysteine were compared in healthy controls with a positive or negative antibody titre against H. pylori. Thirdly, the relation between H. pylori and PAD in individuals with a normal or high homocysteine level was investigated.

Results  A positive immunoglobulin G antibody titre against H. pylori was found in 42% of the PAD patients and in 27% of the controls. The age‐ and socio‐economic‐status (SES) adjusted odds ratio for PAD was 1·5 (95%CI; 1·0–2·2). Additional adjustment for homocysteine plasma concentration did not essentially change the odds ratio. Secondly, among the healthy controls, the homocysteine plasma concentration did not depend on the immunoglobulin G titre, neither did the folate plasma concentration. The concentration of vitamin B12 was slightly higher in women with a positive titre. Thirdly, H. pylori infection was a risk factor for PAD in subjects with a normal homocysteine concentration [OR 2·0 (95%CI 1·3–3·1)].

Conclusions  This study shows a relationship between a positive immunoglobulin G antibody titre against H. pylori and PAD in young women. Moreover, this study does not support the hypothesis that H. pylori infection is related to atherosclerosis via an increase in plasma homocysteine concentration.
Cardiovascular involvement in thalassaemic patients with Pseudoxanthoma elasticum‐like skin lesions: a long‐term follow‐up study
Authors: Cianciulli P. , Sorrentino F. , Maffei L. , Amadori S. , Cappabianca M. P. , Foglietta E. , Carnevali E. , Pasquali‐Ronchetti I.
Published: March 2003

Background Congenital haemolytic anaemia may be associated with pseudoxanthoma elasticum (PXE)‐like clinical manifestations.

Methods The cardiovascular system of 14 homozygous and double heterozygous β‐thalassaemia patients with skin and retinal vessel alterations similar to those in genetic PXE was analysed over a period of 12 years and compared with that of 13 relatives (five sets of parents, one single parent, two thalassaemic brothers), and that of the control group composed of 16, age‐ and sex‐matched, thalassaemic patients.

Results All patients with clinical PXE‐like skin lesions exhibited, by light and electron microscopy, dermal alterations and mineralization of elastic fibres identical to those typical of inherited PXE. None of the relatives and none of the control group showed clinical or structural findings of PXE. The follow‐up started in 1988. After 12 years of clinical observation, six patients showed dramatic progression of skin involvement, angioid streaks had progressed in two subjects. One patient had recurrent gastrointestinal bleeding and underwent partial stomach removal for gastric artery aneurysm, one underwent colon resection for intestinal infarct, one patient had a transitory ischaemic attack, one died after an intracranial haemorrhage, two patients died from cardiovascular disease and one from neoplasia.

Conclusions Thalassaemic patients with PXE‐like skin lesions also manifest PXE‐like vessel alterations that progress with time. Considering the severe outcome of these lesions, accurate monitoring should be routinely performed on the cardiovascular system of thalassaemic patients with PXE‐like skin manifestations.
Effect of endothelin‐1 on intracellular glutathione and lipid peroxide availability and on the secretion of vasoactive substances by human umbilical vein endothelial cells
Authors: Scalera F. , Dittrich R. , Beckmann M. W. , Beinder E.
Published: March 2003

Background The major pathophysiologic changes observed in preeclampsia suggest that endothelial cell dysfunction plays an important role in this disorder. The pathway mediating endothelial cell layer dysfunction is unknown. The concentration of endothelin‐1 (ET‐1), a potent mammalian vasoconstrictor peptide produced by the vascular endothelium, has been observed to be significantly increased in preeclampsia. In this study, we determined the in vitro effect of endothelin‐1 on glutathione and lipid peroxide levels and on the secretion of vasoactive substances by human umbilical vein endothelial cells (HUVECs).

Methods Human umbilical vein endothelial cells were incubated for 24 h in the presence of different concentrations of ET‐1 (0–1000 pmol L−1), which were shown in an earlier experiment to have no effects on vitality and proliferation rate of HUVECs. The levels of glutathione (GSH) and lipid peroxides (LPO) were measured in endothelial cell lysates. For the measurement of vasoactive substances, levels of nitric oxide (NO), prostacyclin (PGI2) and thromboxane A2 (TXA2) were measured in endothelial cell supernatants.

Results At lower concentrations (5–50 pmol L−1), ET‐1 increases the intracellular content of LPO, stimulates the secretion of TXA2, but inhibits the secretion of PGI2 in endothelial cells compared with control cells. At higher concentrations (100–1000 pmol L−1), ET‐1 increases the intracellular content of GSH, but results in a decrease of LPO, and increase of PGI2, back to control levels. ET‐1 has no effect on NO secretion.

Conclusion These findings demonstrate that at concentrations corresponding to values in plasma from preeclamptic women, ET‐1 induces oxidative stress and results in altered secretion of vasoactive substances in human endothelial cells. We conclude that ET‐1 may participate in the pathway leading to endothelial cell dysfunction seen in preeclampsia.
Calcium affects biomarkers of colon carcinogenesis after right hemicolectomy
Authors: Van Gorkom B. A. P. , Van Der Meer R. , Karrenbeld A. , Van Der Sluis T. , Zwart N. , Termont D. S. M. L. , Boersma‐van Ek W. , De Vries E. G. E. , Kleibeuker J. H.
Published: March 2003

Background In Western societies colonic cancer most frequently develops in the distal colon, largely as a result of the composition of the diet. Modulation of dietary factors is therefore an attractive modality to reduce colorectal cancer risk. This study aims to evaluate the potentially protective effects of calcium in right hemicolectomy patients.

Materials and methods A randomized controlled cross‐over intervention trial was performed with 1000 mg of elemental calcium per day for 2 months in 15 right hemicolectomy patients. Primary endpoints were proliferative activity, determined by immunohistochemical detection of BrdU‐labeled cells (LI) in rectal biopsies, and cytotoxicity and alkaline phosphatase activity of faecal water. Secondary endpoints were bile acid composition in faeces.

Results Calcium‐reduced LI in the superficial one‐third of the crypt (from 0·84 ± 0·27% to 0·37 ± 0·08%, P = 0·04) and a trend towards a lower total LI and LI in the mid one‐third of the crypt was observed. Alkaline phosphatase activity was reduced from 6·2 ± 2·6 U mL−1 in the placebo period to 4·6 ± 2·2 in the calcium period (P = 0·02), and a trend toward a lower cytotoxicity of faecal water was observed. No effect on total bile acids in faeces was observed, but calcium increased the percentage of deoxycholic acid (from 49·6 ± 7·0% to 56·5 ± 6·2%, P = 0·03) and decreased the percentages of cholic acid (from 10·3 ± 4·7% to 5·8 ± 2·7%, P = 0·05) and lithocholic acid (from 26·7 ± 3·4% to 23·9 ± 2·9%, P = 0·04).

Conclusion Calcium may have a protective effect against colorectal cancer risk in right hemicolectomy patients.
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

Background 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

Background  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

Background 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

Background 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

Background 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

Background 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

Background 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.
TNFB gene polymorphism in insulin‐dependent diabetes mellitus: association with HLA‐DR alleles
Authors: Newton D. J. , Bowen‐Jones D. , Crosby I. , Barnes R. M. R. , Flanagan B. F.
Published: March 2003

A polymorphism of the TNF‐β gene can be detected by restriction digestion of a PCR product with NcoI. In this study we look at the risk associated with this polymorphism in a study of 69 insulin‐dependent diabetes patients and 119 healthy controls. The risk was further characterized by comparison to the HLA type of the individual, since the TNF polymorphism is in linkage disequilibrium with HLA genes.
A study of HLA‐DPB1 phenotypes reveals DPB1*6301 in a rural population from Cameroon
Authors: Poulton K.V. , Kennedy L.J. , Ross J. , Thomson W. , Mbanya J.C. , Ollier W.E.R.
Published: March 2003

Several recently reported HLA‐DPB1 alleles have only been identified in a single family or individuals and are of unknown distribution world‐wide. Many new DPB1 alleles appear to arise as a result of gene conversion‐like events, which may localize variant DPB1 alleles to the population in which they were first identified. Using two SSOP‐based typing methods in parallel, we have identified HLA‐DPB1*6301 in an individual from rural Cameroon which has previously only been reported in a family of Mexican‐American origin. The presence of DPB1*6301 was confirmed by sequence‐based typing of exon 2.
A novel strategy for unambiguous DPB1 typing
Authors: Varney M. D. , Tait B. D.
Published: March 2003

A DPB1 typing method is described that assigns DPB1 alleles into six groups based on polymorphism at amino acid positions 8–9 and 84–87 using sequence‐specific priming (SSP). The results obtained allow the selection of primers for a subsequent sequence‐specific oligonucleotide (SSO) hybridization procedure which permits DPB1 alleles to be analysed separately in a heterozygote individual. This has greatly reduced the occurrence of typing reaction patterns consistent with multiple combinations of DPB1 alleles seen in other DPB1 typing methods.
HLA‐G and classical HLA class I transcripts in various components of the adult human eye
Authors: Robert P. Y. , Lasalmonie C. , Cogné M. , Adenis J. P. , Drouet M.
Published: March 2003

HLA‐G transcripts have previously been detected in the ocular cell line HS738, in foetal eyes and in global ocular extract. Using RT‐PCR and hybridization, we searched for HLA‐G and classical HLA class I transcripts in the corneas of eye donors (n = 6) and in various components of eyes collected at time of surgery: lens (n = 3), iris (n = 2), vitreous body (n = 2) and retina (n = 2). Whereas HLA class I mRNA was abundant in the ocular tissues of all donors, we could not find HLA‐G transcript in any ocular tissues obtained from subjects in vivo. The absence of HLA‐G in adult eye cornea limits its interest as a possible target in corneal transplantation. Classical HLA class I transcripts were abundant in the cornea and other components of the eye. These results highlight the role of classical HLA class I antigen in eye immunity and corneal transplantation.
Polymorphism of DR52‐associated haplotypes in a Croatian population
Authors: Grubic Z. , Z unec R. , Kas telan A.
Published: March 2003

We 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

We 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

The 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

Alopecia 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

The 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

Adsorption 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.
Aluminium solubility related to secondary solid phases in upper B horizons with spodic characteristics
Authors: SIMONSSON  , BERGGREN
Published: March 2003

We examined the aluminium solubility in the upper B horizon of podzols and its relation to the solid phase of the soil in 60 samples covering a pH range from 3.8 to 5.1. Solid phases were characterized by extractions with acid oxalate and pyrophosphate (pH 10). The solubility of Al was studied in a batch experiment in which samples were equilibrated with 1 mm NaCl at 8°C for 5 days. We also monitored the dissolution kinetics of Al and Si, in some samples. The oxalate and pyrophosphate extractions suggested that secondary Al was mainly organically bound in most soils, and imogolite‐type materials seemed to constitute much of inorganic secondary Al. No single gibbsite or imogolite equilibrium could explain Al3+ activities. In all samples Al solubility, defined as log{Al3+} + 1.65pH, was closely related to the molar ratio of aluminium to carbon in the pyrophosphate extracts (Alp/Cp). Solubility increased with the Alp/Cp ratio until the latter reached ≈ 0.1. This indicated that solubility was controlled by organic complexation, at least when Alp/Cp was small. Silica dissolved slowly in most soils used in the kinetic experiments. We conclude that imogolite‐type materials in the upper B horizon dissolved slowly because of coating with humic substances or ageing or both.
Mathematical morphology for analysing soil structure from images
Authors: HORGAN
Published: March 2003

Mathematical morphology is an approach to image analysis based on set theory. It explores structures by examining the effect of transforming them by set operations. Such operations can be built up and combined into powerful tools for exploring, transforming and measuring the size, shape and connectivity of components of interest in images. Greylevel images are handled by regarding them as binary images in three dimensions. This paper reviews the basic ideas and illustrates them by application to studies of the size distribution of soil pores, the lengths and geometric patterns of cracks in drying soil, and the growth of fungal hyphae. It then extends them in an introductory way to random sets. Practical issues of scale, resolution, sampling, replication and noise in the use of images for soil measurement are described briefly.
Hydraulic conductivity of the matric porosity of an unsaturated vertisol: a field and laboratory comparison
Authors: RUY  , CABIDOCHE
Published: March 2003

In many swelling clay soils several types of porosity can be defined: matric, structural and crack porosities. Measuring the hydraulic conductivity associated with the matric porosity is of major interest because soil movements are governed by matric water flows. Our purpose was to determine the matric conductivity of a vertisol from Guadeloupe (French West Indies) under laboratory and field conditions. We used an Eulerian flow description to measure the conductivity of natural vertisol clods in the laboratory with a drying method. In order to take into account soil movements in every direction, we introduced a tensorial analysis of soil deformations and hydraulic conductivity. The instantaneous profile method was used in the field under wetting conditions. Using soil layer thickness transducers we described water flows in a material coordinate system that can deal with volumetric soil deformations. For wet soil the ratio between the hydraulic conductivity measured in the field and that measured at the laboratory was around 10. However, because the spatial variation of the water content was large, no final conclusion could be drawn to explain this discrepancy. We showed that the gradient of the overburden potential was smaller than that of the matric potential in the field experiment.
Estimating critical state soil mechanics parameters from shear box tests
Authors: KIRBY J. M.
Published: March 2003

Prediction 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.
Effect of clay content and silt—clay fabric on stability of artificial aggregates
Authors: ATTOU F. , BRUAND A. , LE BISSONNAIS Y.
Published: March 2003

The influence of clay content and silt–clay fabric on aggregate stability was investigated. Two silt—clay fabrics were produced in the laboratory by mixing silt particles with a clay phase: (i) a loose packing of the silt particles with clay aggregates, and (ii) a close packing of the silt particles with the dispersed clay phase, the latter coating and bridging the silt particles. Porosity and pore size distribution were measured, and the silt—clay fabric was described using scanning electron microscopy. The aggregate stability was measured under three treatments corresponding to different wetting conditions and energy levels: fast wetting, mechanical breakdown and slow wetting. Our results show that aggregate stability is related to both clay content and silt—clay fabric. Comparison of fragment size distributions and their mean weight diameter amongst the three treatments enabled identification of mechanisms responsible for the variation of aggregate breakdown. The compression of trapped air was the predominant breakdown mechanism for both fast and slow wetting and was related mainly to porosity characteristics. For the mechanical breakdown, the degree of disintegration depended on the cohesion of the silt–clay fabric, which is related to the continuity of the solid phase.
Bromide and herbicide transport under steady‐state and transient flow conditions
Authors: Meyer‐Windel S. , Lennartz B. , Widmoser P.
Published: March 2003

The dynamics of water flow in soils influences the transport behaviour of solutes. Transport of bromide and herbicides through undisturbed soil columns was investigated under conditions of unsaturated steady‐state and transient water flow. Effective transport parameters were obtained from fitting the convection–dispersion equation to curves of concentration against cumulative drainage, and these enabled us to interpret the observed behaviour. Under both steady‐state and transient flow bromide and herbicides were transported through similar parts of the pore volume of a homogeneous single grain soil (Bv horizon). However, in aggregated Ah and Ap horizons preferential transport occurred during transient flow but not during steady‐state flow. For preferential flow the mean transport volume seemed to depend on the prevailing pore system and the fraction of preferentially flowing water. Solute leaching was more efficient under steady‐state than under transient flow for bromide in all soils and for herbicides in the Bv horizon. However, when transient flow caused preferential transport, herbicide loss was greater under transient flow than during steady‐state flow. Under preferential flow conditions a three‐step herbicide concentration development recurred in successive drainage events. This behaviour was not observed for the non‐reactive tracer. It seemed to be caused by sorption. A steady‐state model with cumulative drainage as independent variable instead of time can predict the transport of non‐reactive and adsorbed solutes in homogeneous soils without features of preferential flow. Otherwise constant effective input parameters cannot be assessed a priori.
Efficacy of perforating the soil to capture and store rain during fallow in dry regions
Authors: Cattle S. R.
Published: March 2003

Perforating topsoil of poor conductivity with artificial macropores can often improve the capture and storage of rain in dryland cropping. However, several features can render it of little merit. These include the inability of artificial macropores effectively to harvest coalescing water on the soil surface, and the increased evaporation caused by the greater surface area of subsoil exposed to the atmosphere in such pores. To ascertain the extent of these effects I used a sprinkling infiltrometer to determine the time‐to‐ponding of small areas of perforated and unperforated soil subjected to different intensities of ‘rain’, and determined the rate of evaporation on perforated and unperforated microlysimeters. On average the perforated plots tended to take longer to pond than the unperforated ones, but the water‐harvesting efficacy of individual artificial macropores was highly variable, depending on their position in the microlandscape, the degree of connectivity with subsoil pores, the rate at which the water was applied, and the antecedent water content of the topsoil. The microlysimeter experiments revealed consistently greater evaporation from the perforated samples, with average daily differences between the treatments ranging from 2 to 26%. Antecedent soil water content and air temperature and windspeed affected the amounts of evaporation from both treatments. The ultimate efficacy of perforation for capturing water will vary spatially and temporally according to the extent to which the properties of the soil and environment impact on the behaviour of the penetrating water.