bluuebunny/crossref_metadata_2025 huggingface dataset:
QTL modulating ear size and erectness in pigs
Authors: Wei W. H. , De Koning D. J. , Penman J. C. , Finlayson H. A. , Archibald A. L. , Haley C. S.
Published: May 2007

Ear size and erectness are important conformation measurements in pigs. An F2 population established by crossing European Large White (small, erect ears) with Chinese Meishan (large, flop ears) was used to study the genetic influence of the two ear traits for the first time. A linkage map incorporating 152 markers on 18 autosomal chromosomes was utilised in a genome scan for QTL. Significant QTL were found on SSC1, 5, 7, 9 and 12 for the two traits. The QTL on SSC5 and SSC7 had major effects and were significant at the genome‐wide level (P < 0.01). The QTL on SSC1 for ear erectness also had a major effect and was genome‐wide significant (P < 0.01). The 95% confidence interval (CI) of the ear size QTL on SSC5 spanned only 4 cM. The QTL on SSC7 for the two ear traits each had a CI of <20 cM, and their positions overlapped with those of the major QTL affecting subcutaneous fat depths on the same chromosome. This study provides insights on the complex genetic influences underlying pig ear traits and will facilitate positional candidate gene analysis to identify causative DNA variants.
A genome scan reveals QTL for growth, fatness, leanness and meat quality in a Duroc‐Pietrain resource population
Authors: Liu G. , Jennen D. G. J. , Tholen E. , Juengst H. , Kleinwächter T. , Hölker M. , Tesfaye D. , Ün G. , Schreinemachers H.‐J. , Murani E. , Ponsuksili S. , Kim J.‐J. , Schellander K. , Wimmers K.
Published: May 2007

We performed a genome‐wide QTL scan for production traits in a line cross between Duroc and Pietrain breeds of pigs, which included 585 F2 progeny produced from 31 full‐sib families genotyped with 106 informative microsatellites. A linkage map covering all 18 autosomes and spanning 1987 Kosambi cM was constructed. Thirty‐five phenotypic traits including body weight, growth, carcass composition and meat quality traits were analysed using least square regression interval mapping. Twenty‐four QTL exceeded the genome‐wide significance threshold, while 47 QTL reached the suggestive threshold. These QTL were located at 28 genomic regions on 16 autosomal chromosomes and QTL in 11 regions were significant at the genome‐wide level. A QTL affecting pH value in loin was detected on SSC1 between marker‐interval S0312‐S0113 with strong statistical support (P < 3.0 × 10−14); this QTL was also associated with meat colour and conductivity. QTL for carcass composition and average daily gain was also found on SSC1, suggesting multiple QTL. Seventeen genomic segments had only a single QTL that reached at least suggestive significance. Forty QTL exhibited additive inheritance whereas 31 QTL showed (over‐) dominance effects. Two QTL for trait backfat thickness were detected on SSC2; a significant paternal effect was found for a QTL in the IGF2 region while another QTL in the middle of SSC2 showed Mendelian expression.
The extent of linkage disequilibrium in a large cattle population of western Africa and its consequences for association studies
Authors: Thévenon S. , Dayo G. K. , Sylla S. , Sidibe I. , Berthier D. , Legros H. , Boichard D. , Eggen A. , Gautier M.
Published: May 2007

Several previous studies concluded that linkage disequilibrium (LD) in livestock populations from developed countries originated from the impact of strong selection. Here, we assessed the extent of LD in a cattle population from western Africa that was bred in an extensive farming system. The analyses were performed on 363 individuals in a Bos indicus × Bos taurus population using 42 microsatellite markers on BTA04, BTA07 and BTA13. A high level of expected heterozygosity (0.71), a high mean number of alleles per locus (9.7) and a mild shift in Hardy–Weinberg equilibrium were found. Linkage disequilibrium extended over shorter distances than what has been observed in cattle from developed countries. Effective population size was assessed using two methods; both methods produced large values: 1388 when considering heterozygosity (assuming a mutation rate of 10−3) and 2344 when considering LD on whole linkage groups (assuming a constant population size over generations). However, analysing the decay of LD as a function of marker spacing indicated a decreasing trend in effective population size over generations. This decrease could be explained by increasing selective pressure and/or by an admixture process. Finally, LD extended over small distances, which suggested that whole‐genome scans will require a large number of markers. However, association studies using such populations will be effective.
Mitochondrial DNA analyses of Indian water buffalo support a distinct genetic origin of river and swamp buffalo
Authors: Kumar S. , Nagarajan M. , Sandhu J. S. , Kumar N. , Behl V. , Nishanth G.
Published: May 2007

Water buffalo (Bubalus bubalis) is broadly classified into river and swamp categories, but it remains disputed whether these two types were independently domesticated, or if they are the result of a single domestication event. In this study, we sequenced the mitochondrial D‐loop region and cytochrome b gene of 217 and 80 buffalo respectively from eight breeds/locations in northern, north‐western, central and southern India and compared our results with published Mediterranean and swamp buffalo sequences. Using these data, river and swamp buffalo were distinguished into two distinct clades. Based upon the existing knowledge of cytogenetic, ecological and phenotypic parameters, molecular data and present‐day distribution of the river and swamp buffalo, we suggest that these two types were domesticated independently, and that classification of the river and swamp buffalo as two related subspecies is more appropriate.
Matched‐related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant Research
Authors: Panepinto Julie A. , Walters Mark C. , Carreras Jeanette , Marsh Judith , Bredeson Christopher N. , Gale Robert Peter , Hale Gregory A. , Horan John , Hows Jill M. , Klein John P. , Pasquini Ricardo , Roberts Irene , Sullivan Keith , Eapen Mary , Ferster Alina ,   On behalf of the Non‐Malignant Marrow Disorders Working Committee, Center for International Blood and Marrow Transplant Research
Published: May 2007

We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)‐matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso‐occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received >10 red blood cell transfusions before HCT. Twenty‐seven percent of patients had a poor performance score at transplantation. Ninety‐four percent received busulfan and cyclophosphamide‐containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post‐transplant period. Rates of acute and chronic graft‐versus‐host disease were 10% and 22% respectively. Sixty‐four of 67 patients are alive with 5‐year probabilities of disease‐free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle‐related events. This report confirms and extends earlier reports that HCT from HLA‐matched related donors offers a very high survival rate, with few transplant‐related complications and the elimination of sickle‐related complications in the majority of patients who undergo this therapy.
A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR® (long‐acting repeatable octreotide) in the primary therapy of patients with acromegaly
Authors: Mercado Moises , Borges Fatima , Bouterfa Hakim , Chang Tien‐Chun , Chervin Alberto , Farrall Andrew J. , Patocs Attila , Petersenn Stephan , Podoba Jan , Safari Mitra , Wardlaw Joanna ,   on behalf of the SMS995B2401 Study Group
Published: May 2007

Objective  To evaluate the efficacy, safety and tolerability of octreotide LAR® (long‐acting repeatable octreotide) in the primary therapy of acromegaly.

Design and patients  Ninety‐eight previously untreated acromegalics were recruited into this prospective multicentre study. A total of 68 patients successfully completed 48 weeks of the study period, received 12 doses of octreotide LAR 10–30 mg every 4 weeks, and constituted the population used for this analysis.

Measurements and results  A clinically relevant reduction (i.e. to ≤ 5 µg/l) in mean GH (mGH) was recorded in 72% of patients after 24 weeks of treatment, and 42% reached a ‘safe’ GH value (≤ 2·5 µg/l). At week 48, 16 more patients were considered partial GH responders (GH > 2·5 µg/l and ≤ 5 µg/l) and 44% had reached a GH level ≤ 2·5 µg/l. IGF‐1 levels normalized in 38% and 34% of patients after 24 and 48 weeks of treatment, respectively. At study completion, 10 patients (14·7%) who had not normalized their IGF‐1 levels had achieved at least a 50% decrement in this marker. In eight microadenoma patients, tumour volume decreased from a mean baseline level of 298 ± 145 mm3 to 139 ± 94 mm3 after 24 weeks and to 99 ± 70 mm3 after 48 weeks of therapy. In 60 patients with macroadenoma, the corresponding values were 3885 ± 5077 mm3 at baseline and 2723 ± 3435 and 2406 ± 3207 mm3 after 24 and 48 weeks, respectively. At weeks 24 and 48, a significant (> 20%) tumour volume reduction was reported in 63% and 75% of patients, respectively. A reduction in the severity of symptoms of acromegaly was observed early in treatment and was maintained throughout the study period.

Conclusion  Octreotide LAR represents a viable alternative to surgery for primary treatment of acromegaly leading to a progressive regression of tumour volume, a sustained control of biochemical abnormalities and an adequate relief of symptoms of the disease.
Radioiodine treatment for benign thyroid diseases
Authors: Weetman Anthony P.
Published: May 2007

Radioiodine has been in use for over 60 years as a treatment for hyperthyroidism. Major changes in clinical practice have occurred with the realization that accurate dosimetry is incapable of avoiding the risks of hypothyroidism, while more accurate assessment of the risks of other adverse effects of radioiodine such as ophthalmopathy and carcinogenesis have become available. More is also known of the potential for pretreatment with an antithyroid drug to affect the outcome of radioiodine treatment. However, we are still uncertain of the benefits of radioiodine treatment in subclinical hyperthyroidism.

 During the last two decades there has been wider acceptance of radioiodine as a safe and effective therapy for benign, nontoxic goitre, coupled with waning enthusiasm for the use of levothyroxine, as the risks and benefits of this option have become more apparent. The use of recombinant TSH offers the prospect that radioiodine treatment of nontoxic goitre can be simplified and improved, although more studies of this strategy are urgently required.
l‐selectin gene polymorphisms in Graves' disease
Authors: Chen Hao‐Yan , Cui Bin , Wang Shu , Zhao Ze‐Fei , Sun Hua , Zhao Yong‐Ju , Li Xiao‐Ying , Ning Guang
Published: May 2007

Objective   Graves’ disease (GD) is an autoimmune disorder with genetic predisposition. There is strong evidence that members of the selectin family participate in the interaction between leucocytes and the endothelium, as well as in inflammatory cell recruitment. Moreover, a high serum level of a soluble form of l‐selectin (sl‐selectin) has been reported in untreated GD patients. However, the impact of l‐selectin polymorphisms on GD has not yet been investigated. The aim of the present study was to elucidate whether l‐selectin gene polymorphisms were associated with the development of GD.

Subjects and design  l‐selectin gene polymorphisms were investigated in 230 Chinese GD patients and 208 healthy control subjects without antithyroid autoantibodies or a family history of autoimmune disorders. Two l‐selectin SNPs were genotyped by the PCR‐restriction fragment length polymorphism (PCR‐RFLP) method.

Results  A C/T polymorphism at position –642 of the promoter region and a Pro213Ser (c.725 C‐T) polymorphism in exon 6 were examined using PCR‐RFLP. There was a significant increase in –642T allele frequency in GD patients compared with healthy controls (70 vs. 62%; P = 0·0126; Pc = 0·0252). The frequency of the c.725C allele in exon 6 also appeared higher in GD patients than in controls. Haplotype analysis showed a significant decrease in the –642C/c.725T haplotype in GD patients (26 vs. 34%; P = 0·0095; Pc = 0·0190). However there was no association between polymorphisms and certain GD clinical phenotypes, including age of onset and ophthalmopathy.

Conclusions  l‐selectin gene polymorphisms are associated with GD susceptibility in Chinese patients.
Molecular evidence‐based medicine
Authors: Ioannidis J. P. A.
Published: May 2007

Evidence‐based medicine and molecular medicine have both been influential in biomedical research in the last 15 years. Despite following largely parallel routes to date, the goals and principles of evidence‐based and molecular medicine are complementary and they should be converging. I define molecular evidence‐based medicine as the study of medical information that makes sense of the advances of molecular biological disciplines and where errors and biases are properly appreciated and placed in context. Biomedical measurement capacity improves very rapidly. The exponentially growing mass of hypotheses being tested requires a new approach to both statistical and biological inference. Multidimensional biology requires careful exact replication of research findings, but indirect corroboration is often all that is achieved at best. Besides random error, bias remains a major threat. It is often difficult to separate bias from the spirit of scientific inquiry to force data into coherent and ‘significant’ biological stories. Transparency and public availability of protocols, data, analyses and results may be crucial to make sense of the complex biology of human disease and avoid being flooded by spurious research findings. Research efforts should be integrated across teams in an open, sharing environment. Most research in the future may be designed, performed, and integrated in the public cyberspace.
The PPARδ agonist GW501516 suppresses interleukin‐6‐mediated hepatocyte acute phase reaction via STAT3 inhibition
Authors: Kino T. , Rice K. C. , Chrousos G. P.
Published: May 2007

Background  Interleukin‐6 and downstream liver effectors acute phase reactants are implicated in the systemic inflammatory reaction. Peroxisome proliferator‐activated receptor δ (PPARδ), which binds to and is activated by a variety of fatty acids, was recently shown to have anti‐inflammatory actions.

Materials and methods  We examined the ability of the synthetic PPARδ agonist GW501516 to suppress interleukin‐6‐induced expression of acute phase proteins in human hepatoma HepG2 cells and rat primary hepatocytes.

Results  GW501516 dose‐dependently suppressed interleukin‐6‐induced mRNA expression of the acute phase protein α1‐antichymotrypsin in HepG2 cells. The compound also suppressed interleukin‐6‐induced mRNA expression of α2‐acid glycoprotein, β‐fibrinogen and α2‐macroglobulin in and the secretion of C‐reactive protein by rat primary hepatocytes. Depletion of the PPARδ receptor, but not of PPARα or γ, attenuated the suppressive effect of GW501516 on interleukin‐6‐induced α1‐antichymotrypsin mRNA expression, indicating that PPARδ specifically mediated this effect. Since interleukin‐6 stimulates the transcriptional activity of the α1‐antichymotrypsin promoter by activating the signal transducer and activator of transcription (STAT) 3, we examined functional interaction of this transcription factor and PPARδ on this promoter. Overexpression of PPARδ enhanced the suppressive effect of GW501516 on STAT3‐activated transcriptional activity of the α1‐antichymotrypsin promoter, while GW501516 suppressed interleukin‐6‐induced binding of this transcription factor to this promoter.

Conclusions  These findings indicate that agonist‐activated PPARδ interferes with interleukin‐6‐induced acute phase reaction in the liver by inhibiting the transcriptional activity of STAT3. PPARδ agonists might be useful for the suppression of systemic inflammatory reactions in which IL‐6 plays a central role.
Endothelial dysfunction in a murine model of thyroid hormone resistance
Authors: Owen P. J. D. , Ying H. , Lang D. , Tomlinson D. , Lewis M. J. , Cheng S. Y. , Lazarus J. H.
Published: May 2007

Background  The development of a knockin mouse model of resistance to thyroid hormone (RTH) has led to a greater understanding of both the molecular and clinical behaviour of this syndrome. We have investigated the vascular response in RTH using a specific (TRβ PV) knockin mouse model targeting the PV mutation to the thyroid hormone receptor β gene locus.

Materials and methods  Ring segments of the thoracic aorta were used to assess the response of homozygous, heterozygous and wild‐type controls to contractile agents, potassium chloride and phenylephrine. Each genotype after maximal contraction was exposed to increasing concentrations of relaxing agents, acetylcholine (ACh) and sodium nitroprusside (SNP).

Results  The response of these aortic ring segments to ACh and SNP demonstrates that endothelium‐dependent relaxation to ACh was significantly impaired in both heterozygous and homozygous mice compared to controls (69·8 ± 2·0%, 59·7 ± 1·4% and 75·0 ± 1·7%, respectively; P < 0·001). However, endothelium independent responses to SNP showed no difference between genotypes (114·4 ± 3·2%, 116·8 ± 2·6% and 106·9 ± 4·9%; P = NS).

Conclusion  These data suggest that endothelial function is impaired in the RTH mouse aorta. The respective roles of elevated thyroid stimulating hormone (TSH), elevated thyroid hormone concentrations and the mutated thyroid hormone β receptor require further elucidation.
Alteration of bone cell function by RANKL and OPG in different in vitro models
Authors: Lin J. M. , Callon K. E. , Lin C. Q. , Bava U. , Zheng M. H. , Reid I. R. , Cornish J.
Published: May 2007

Background  Receptor activator of nuclear factor‐κB ligand (RANKL) and osteoprotegerin (OPG) are well‐documented potent regulators of osteoclast development. However, their effects in mature bone cells and in organ cultures have not been well studied. It is uncertain whether their activities in different experimental models are comparable.

Materials and methods  RANKL and OPG were evaluated for their activities in mouse calvarial organ cultures, mouse bone marrow cultures, isolated rat mature osteoclast assays and rat primary osteoblast cultures.

Results  In murine calvarial organ culture, both muRANKL (≥ 10 ng mL−1) and rRANKL (≥ 100 ng mL−1) significantly stimulated 45Ca release, while OPG (≥ 50 ng mL−1) was an inhibitor of bone resorption. Meanwhile, [3H]‐thymidine incorporation in this assay was also modulated (indicating proliferation increases in the osteoblast lineage of cells) although these peptides had no direct effect on [3H]‐thymidine incorporation in isolated osteoblast assays. In mouse bone marrow cultures, muRANKL (≥ 1 ng mL−1) and rRANKL (≥ 5 ng mL−1) significantly stimulated osteoclastogenesis. The number of nuclei per osteoclast was also significantly increased. OPG strongly inhibited this index, with over 90% suppression at 1 ng mL−1. Both muRANKL (10 ng mL−1) and rRANKL (100 ng mL−1) stimulated, while OPG (10 ng mL−1) inhibited osteoclast activity in isolated mature osteoclast assays.

Conclusion  The current study demonstrated that bone resorption modulated by RANKL and OPG, in murine calvarial organ culture, leads to changes in osteoblast proliferation, suggesting a feedback mechanism from osteoclasts to osteoblasts. In addition, it was found that RANKL and OPG have more potent effects on osteoclastogenesis than on the activity of mature osteoclasts.
NF‐κB and apoptosis in colorectal tumourigenesis
Authors: Aranha M. M. , Borralho P. M. , Ravasco P. , Moreira da Silva I. B. , Correia L. , Fernandes A. , Camilo M. E. , Rodrigues C. M. P.
Published: May 2007

Background  Nuclear factor‐κB (NF‐κB) may play an important role in colorectal tumourigenesis, controlling cell cycle and apoptosis gene expression. In addition, imbalances between cell proliferation and cell death are thought to underlie neoplastic development. The aims of this study were to investigate apoptosis and expression of several apoptosis‐related proteins, and to determine correlations with colorectal tumour progression.

Materials and methods  Apoptosis was evaluated by the TUNEL assay in 48 patient samples, including adenomas, adenocarcinomas and adjacent normal mucosas. Immunohistochemistry was performed for Bcl‐2 and NF‐κB. Expression levels of p53, Bax and IκB proteins were determined by immunoblotting. Cultured human colon cancer cells were used to evaluate NF‐κB expression and nuclear translocation by immunocytochemistry and immunoblotting.

Results  Apoptosis and NF‐κB immunoreactivity were significantly higher in tumour tissue compared with normal mucosa (P < 0·01), increasing in association with histological tumour progression (P < 0·01). Bcl‐2 was consistently higher in normal mucosa (P < 0·01) and inversely correlated with the percentage of apoptosis (P < 0·01). Phosphorylated p53 and Bax levels were similar in tumour tissue and normal mucosa; however, the NF‐κB inhibitor, IκB, tended to decrease in tumours. In vitro, nuclear translocation of NF‐κB was greater in proliferative than in resting phases of colon cancer cells.

Conclusions  NF‐κB expression and apoptosis are increased from adenoma to poorly differentiated adenocarcinoma tissues. Apoptosis is correlated with suppression of Bcl‐2 expression, but appears to proceed through a p53‐ and Bax‐independent pathway. Activation of NF‐κB may play an important role in colorectal tumour progression.
Development of a heterologous, multigenotype vaccine against hepatitis C virus infection
Authors: Encke J. , Radunz W. , Eisenbach C. , Geib J. , Gehrke S. , Pfaff E. , Stremmel W.
Published: May 2007

Background Unquestionably viral diversity and genetic heterogeneity in hepatitis C virus (HCV) infection and other viral diseases play an essential role in viral immune escape and the development of chronicity. Despite this knowledge most vaccine approaches against HCV have excluded this important issue. Moreover the feasibility of developing an effective HCV vaccine has been questioned, mainly because prophylactic immunity against HCV cannot be achieved in chimpanzees by either vaccination or previous HCV infection, and reinfection in men has been reported, most likely due to genetic shift and immune escape. To analyse and characterize a new technique of a ‘multigenotype’‐ and/or ‘library’‐vaccine, we established an envelope 1 (E1) plasmid vaccine against HCV and characterized humoral and cellular immune responses after vaccination in a mouse model.

Material and methods Normally genetic information of one or two target proteins is cloned into a DNA‐vaccine. In our approach we cloned a defined number of different genotypes and subtypes (defined vaccine, DV) or the genetic information from 20 patients (undefined) into a plasmid (library vaccine, LV).

Results As expected, immunized animals showed both stronger humoral (ELISA) and cellular (T‐cell proliferation, ELISPOT) immune responses against genotype 1, since the stimulating antigen was genotype 1 derived. However, not all genotype 1 immunized animals recognized this viral antigen leading to the assumption that some epitopes lost their immunogenicity through a change in the amino acid sequence. Interestingly, some of the genotype 4 and 5 immunized mice sera were able to react against E1 protein.

Conclusion Most of the assays showed immune reactivity against the DV or LV vaccine demonstrating the cross‐reactive potential of such a vaccination approach. This cloning and immunization strategy based on the viral heterogeneity of the virus has in our view major implications for HCV, a virus with a broad viral genetic diversity, and may become in the future in the context of DNA‐ or viral‐based vaccination strategies a possibility to overcome viral immune escape both in the prophylactic or therapeutic setting.
Elevated levels of interleukin‐1β‐converting enzyme and caspase‐cleaved cytokeratin‐18 in acute myocardial infarction
Authors: Adlbrecht C. , Hoetzenecker K. , Posch M. , Steiner S. , Kopp C. , Hacker S. , Auer J. , Horvath R. , Moser B. , Roth G. , Wolner E. , Lang I. M. , Ankersmit H. J.
Published: May 2007

Background  Systemic inflammation and apoptosis‐specific immune activation play a major role in acute coronary syndromes (ACS) including acute myocardial infarction (AMI). The role of systemic and coronary obtained inflammatory plasma protein interleukin‐1β precursor (IL‐1βp), IL‐1β‐converting enzyme (ICE) and the apoptosis‐specific caspase‐cleaved cytokeratin‐18 (ccCK‐18) are not known in ACS.

Materials and methods  Plasma samples were obtained from stable angina (SA, n = 34), unstable angina (UA, n = 37) and patients with AMI (n = 39). Coronary blood was acquired by means of thrombectomy devices (X‐sizer) in AMI patients. IL‐1βp, ICE and ccCK‐18 were determined by enzyme‐linked immunosorbent assay (ELISA). Group comparisons were evaluated by parametric Tukey test. Multivariate logistic regression analysis was performed to determine predictive values of IL‐1βp, ICE and ccCK‐18 as compared to creatine kinase (CK) and troponin T (TnT) in order to relate these markers with the occurrence of myocardial damage.

Results  IL‐1βp, ICE and ccCK‐18 were identified to be significantly altered in the peripheral blood of patients suffering from AMI as compared to SA and UA. ROC curves were plotted and revealed that ccCK‐18 is a novel sensitive marker for the detection of myocardial damage as compared to TnT or CK. (AUC ccCK‐18 0·925, TnT AUC 0·62 and CK AUC 0·858.) Moreover, ICE and ccCK‐18 were significantly increased at the site of coronary occlusion as compared to peripheral blood samples in AMI patients (both P < 0·001).

Conclusion  Our data suggest that ACS is related to increased concentration of systemic soluble ICE and ccCK‐18. Moreover, soluble ccCK‐18 was identified to be a superior marker as compared to TnT or CK, for detection of myocardial damage.
Endothelial function in familial combined hyperlipidaemia
Authors: Ter Avest E. , Holewijn S. , Van Tits L. J. H. , De Wit H. M. , Stalenhoef A. F. H. , De Graaf J.
Published: May 2007

Background  Familial combined hyperlipidaemia (FCH) is characterized by dyslipidaemia, visceral obesity and insulin resistance, and is associated with an increased intima‐media thickness (IMT) and an increased risk for cardiovascular disease. In the present study, we investigated whether FCH is associated with early functional vascular wall changes, as represented by endothelial dysfunction, and we determined whether endothelial function in FCH is related to any of the cardiovascular risk factors associated with the FCH phenotype, or to the (increased) IMT.

Design  In 98 patients with FCH [mean age 51 (48–54) years, 43% male] and 230 unaffected relatives [mean age 44 (42–46) years, 48% male], venous blood was drawn in the fasting state after discontinuation of lipid lowering drugs for at least 4 weeks (if used). IMT was measured by B‐mode ultrasound and endothelial function was assessed by determination of flow mediated dilation (FMD) and by measurement of plasma concentrations of various soluble adhesion molecules, including soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM) and soluble E‐selectin.

Results  There were no significant differences between FCH patients and their non‐affected relatives in FMD [2·9 (2·3–3·6%) vs. 2·8 (2·5–3·2%)] or in the plasma concentrations of the various adhesion molecules. None of the individual clinical and biochemical cardiovascular risk factors was an independent predictor of endothelial function in patients with FCH, nor was IMT. However, subgroup analysis revealed that IMT was an independent and powerful predictor of FMD in subjects with carotid artery plaques (St. β = 4·11, P < 0·004), whereas IMT was no significant predictor in subjects without plaques.

Conclusions  FCH patients have no impaired endothelial function when compared to their unaffected relatives. IMT is an important predictor of FMD when advanced morphological wall changes are present. Our results question the value of FMD measurements for cardiovascular risk stratification in populations with an anticipated high cardiovascular risk.
A review of non‐equilibrium water flow and solute transport in soil macropores: principles, controlling factors and consequences for water quality
Authors: Jarvis N. J.
Published: May 2007

This review discusses the causes and consequences of ‘non‐equilibrium’ water flow and solute transport in large structural pores or macropores (root and earthworm channels, fissures and interaggregate voids). The experimental evidence suggests that pores larger thanc. 0.3 mm in equivalent cylindrical diameter allow rapid non‐equilibrium flow. Apart from their large size and continuity, this is also due to the presence of impermeable linings and coatings that restrict lateral mass exchange. Macropores also represent microsites in soil that are more biologically active, and often more chemically reactive than the bulk soil. However, sorption retardation during transport through such pores is weaker than in the bulk soil, due to their small surface areas and significant kinetic effects, especially in larger macropores. The potential for non‐equilibrium water flow and solute transport at any site depends on the nature of the macropore network, which is determined by the factors of structure formation and degradation, including the abundance and activity of soil biota such as earthworms, soil properties (e.g. clay content), site factors (e.g. slope position, drying intensity, vegetation) and management (e.g. cropping, tillage, traffic). A conceptual model is proposed that summarizes these effects of site factors on the inherent potential for non‐equilibrium water flow and solute transport in macropores. Initial and boundary conditions determine the extent to which this potential is realized. High rain intensities clearly increase the strength of non‐equilibrium flow in macropores, but the effects of initial water content seem complex, due to the confounding effects of soil shrinkage and water repellency. The impacts of macropore flow on water quality are most significant for relatively immobile solutes that are foreign to the soil and whose effects on ecosystem and human health are pronounced even at small leached fractions (e.g. pesticides). The review concludes with a discussion of topics where process understanding is still lacking, and also suggests some potential applications of the considerable knowledge that has accumulated in recent decades.
Variable carbon recovery of Walkley‐Black analysis and implications for national soil organic carbon accounting
Authors: Lettens S. , De Vos B. , Quataert P. , Van Wesemael B. , Muys B. , Van Orshoven J.
Published: May 2007

There is considerable interest in the computation of national and regional soil carbon stocks, largely as the result of the provisions of the Kyoto Protocol. Such stocks are often calculated and compared without proper reference to the uncertainties induced by different analytical methodologies. We illustrate the nature and magnitude of these uncertainties with the present soil organic carbon (SOC) study in Belgium. TheSOCrecovery of the Walkley‐Black method was investigated based on a database of 475 samples of silt loam and sandy soils, which cover different soil depths and vegetation types in northern Belgium. The organic carbon content of the soil samples was measured by the original Walkley‐Black method and by a total organic carbon analyser. The recovery was computed as the ratio of these two results per soil sample. Land use, texture and soil sampling depth had a significant influence on the recovery as well as their three‐way interaction term (land use × texture × sampling depth). The impact of a land use, texture and sampling depth dependent Walkley‐Black correction on the year 2000SOCinventory of Belgium was determined by regression analysis. Based on new correction factors, the nationalSOCstocks increased by 22% for the whole country, ranging from 18% for cropland to 31% for mixed forest relative to the standard correctedSOCinventory. The new recovery values influenced therefore not only C stocks in the year 2000, but also the expectedSOCchange following land use change. Adequate correction of Walkley‐Black measurements is therefore crucial for the absolute and comparativeSOCassessments that are required for Kyoto reporting and must be computed to take into account the regional status of soil and land use. ‘Universal’ corrections are probably an unrealistic expectation.
Factors controlling the water repellency induced by fire in calcareous Mediterranean forest soils
Authors: Arcenegui V. , Mataix‐Solera J. , Guerrero C. , Zornoza R. , Mayoral A. M. , Morales J.
Published: May 2007

Water repellency (WR) is a property affected by fire and of crucial importance in the hydrological behaviour of soils after burning. In dry Mediterranean areas knowledge of the factors that control the development of water repellency by fire is of particular interest. We examined such factors in two calcareous soils, a Regosol and a Luvisol, representative of forest areas of southeast Spain. Heating temperature (200–500°C), vegetation type (Rosmarinus officinalis, Pinus halepensis and Brachypodium retusum), quantity of vegetation litter (control, low and high) and type of soil were selected as factors for assessing the WR induced by fire. The two soils exhibited markedly different WR responses after heating, the Regosol being much more susceptible than the Luvisol. Characteristics such as organic matter and clay content seem to determine the different WR responses to heating. We found that the type and quantity of vegetation litter also control the persistence of induced WR. In general, the order of increasing WR was Brachypodium < Pinus < Rosmarinus, and larger amounts of litter induced more WR. Maximum values of WR, most of them classified as severe (901−3600 s), were found in the range of 300−350°C, whereas beyond this temperature WR was destroyed. These results show that water repellency induced by combustion could be limited by environmental factors such as vegetation type and availability of litter, and that soil type and its characteristics also play a decisive role.
Variation of chemical properties as affected by soil erosion on hillslopes and terraces
Authors: Ni S. J. , Zhang J. H.
Published: May 2007

The variation in soil nutrients is crucial to the understanding of productivity of soil undergoing erosion overall, as the latter can result in a decline in soil quality and crop production in the whole landscape. Two toposequences (a long slope and terraced field series) were selected from hilly areas of the Sichuan Basin, China, to determine the effects of soil redistribution rates and topographic changes on P, K and CaCO3 contents, and examine the contribution of water and tillage erosion to the variation and distribution pattern in these chemical properties within different landscapes. For the long slope, soil loss occurred at upper slope positions and soil accumulation was present at lower slope positions. However, terrace banks create a line of zero downslope transport of soil, and lead to abrupt changes in 137Cs inventories over very short distances between the upper (or lower) part of the terrace and the lower (or upper) part of the neighbouring terrace. Extractable K concentrations are significantly related to 137Cs inventories on both the long slope and terraced fields, which suggests that the distribution of extractable K is closely linked to soil redistribution. However, it is noticeable that no close relationship between extractable P concentrations and 137Cs inventories was found on the terraced fields, while there was a highly significant correlation between the two variables on the long slope. The variation in extractable P by soil redistribution was enhanced on the long slope, but was concealed on the terraced fields due to the presence of CaCO3. It is suggested that the variation in extractable P not only depends on soil redistribution in relation to fine soil particles, but is also influenced by other factors such as P‐fixation onto CaCO3, the concentration of which itself is linked to soil erosion and redistribution. Therefore, extractable P dynamics with reference to soil erosion are relatively complex on carbonate‐rich soil and parent materials in areas such as those represented by the Sichuan Basin. Tillage erosion, the dominant soil redistribution process on terraced fields, was found to be a major contributor to the variation in soil chemical properties in the terraced field landscape, while water erosion plays an important role in the variation in soil chemical properties in the long slope landscape. In the case of carbonate‐rich soils or parent materials, however, tillage erosion did not create accumulations of extractable P in depressions, whereas water erosion results in extractable P losses at upper slope positions and accumulation at lower slope positions.
Percutaneous coronary intervention with stent implantation in haemophilic A patient with unstable angina
Authors: SMOLKA G. , KULACH A. , DABEK J. , SZULC A. , GASIOR Z.
Published: May 2007

Summary.  The prevalence of coronary artery disease (CAD) and acute coronary syndromes in patients with haemophilia is much lower than in general population and there is a lack of information regarding safe interventional or surgical treatment of CAD in haemophiliacs. This report presents a case of patient with moderate haemophilia A and unstable angina pectoris, who underwent successful coronary angioplasty. The patient was pretreated with factor VIII (before and after the procedure) and the incision site was sealed with vessel closure device. Additionally, the article discusses the issue of the safety of standard, postpercutaneous coronary intervention antiplatelet therapy in patients with haemophilia.
C1584 in von Willebrand factor is necessary for enhanced proteolysis by ADAMTS13 in vitro
Authors: KEENEY S. , GRUNDY P. , COLLINS P. W. , BOWEN D. J.
Published: May 2007

Summary.  The cysteine variant of the amino acid change tyrosine/cysteine 1584 (Y/C1584) in von Willebrand factor (VWF) has previously been shown to cosegregate with increased susceptibility of VWF to proteolysis by ADAMTS13. It is not known whether C1584 itself confers increased proteolysis or is linked to a causative change elsewhere in VWF. To address whether C1584 underlies enhanced susceptibility of VWF to ADAMTS13‐mediated proteolysis, a single family comprising two heterozygous Y/C1584 individuals and four homozygous Y/Y1584 individuals was investigated. The essential regions of the VWF gene were sequenced in all six individuals and ADAMTS13‐mediated proteolysis of plasma VWF was assessed for each individual. Comparison of the VWF coding sequences for the Y/C1584 individuals with those for the Y/Y1584 individuals revealed that two amino acid variants were unique to the heterozygotes: R484 and C1584. The plasma VWF of the two heterozygotes showed increased susceptibility to proteolysis in vitro compared with that of the four homozygotes. In the present study we demonstrate that R484, in the absence of C1584, does not influence VWF proteolysis. Enhanced proteolysis occurred only in the presence of Cys1584. Thus, Cys1584 is necessary for increased susceptibility of VWF to proteolysis by ADAMTS13.
Safety and efficacy of a sucrose‐formulated recombinant factor VIII product for the treatment of previously treated patients with haemophilia A in China
Authors: SHI J. , ZHAO Y. , WU J. , SUN J. , WANG L. , YANG R.
Published: May 2007

Summary.  The use of plasma‐derived products has contributed to a high rate of blood‐borne infections among haemophilia patients in China. Recombinant factor VIII (rFVIII) products that are manufactured without human or bovine albumin and include dedicated viral inactivation steps, hold a significant safety advantage over plasma products. However, there is little information published on the use of rFVIII products in non‐caucasian populations. This is the first reported evaluation of the efficacy and safety of a rFVIII product in Chinese haemophiliacs.

An open‐label, non‐randomized, prospective, multicentre trial enroled previously treated Chinese patients with haemophilia A. All treatments were administered using a sucrose‐formulated rFVIII‐FS (Kogenate®).

Forty‐nine patients received totals of 291 infusions (mean, 5.94/patient) and 742 140 IU rFVIII‐FS (mean, 2550.3 IU/infusion). Of the 60 acute bleeding episodes that were treated, 90% were successfully managed with only one (81.7%) infusion or two (8.3%) infusions. Physicians reported haemostasis control for acute bleeds to be ‘Excellent’ or ‘Improved’ with rFVIII‐FS therapy. No FVIII inhibitors were detected in any patient. Only one treatment‐related adverse event was reported, which was mild dizziness that resolved spontaneously. rFVIII‐FS was efficacious, safe and well tolerated in the treatment of previously treated patients with haemophilia A in China.
Expression of granzyme A in human polymorphonuclear neutrophils
Authors: Hochegger Kathrin , Eller Philipp , Huber Julia M. , Bernhard David , Mayer Gert , Zlabinger Gerhard J. , Rosenkranz Alexander R.
Published: May 2007

Polymorphonuclear neutrophils (PMNs) are the first line of defence against invading pathogens. They contain a multitude of antimicrobial and potentially cytotoxic substances packed in granules and secretory vesicles. Here, we show that granzyme A (GzmA) is constitutively expressed in human PMNs, but not in the promyelocytic cell line HL‐60, by performing flow cytometry, western blot, enzyme‐linked immunosorbent assay and quantitative polymerase chain reaction. To further track the intracellular localization of GzmA, we performed subcellular fractionation and found GzmA to be present in peroxidase‐negative granules. Finally, stimulation with opsonized Escherichia coli or the bioincompatible haemodialysis membrane cuprophane led to up‐regulation of GzmA expression at the transcriptional level as well as at the translational level. In conclusion, we provide clear evidence that GzmA is constitutively expressed in human PMNs and can be up‐regulated upon stimulation. These findings may also indicate a role for GzmA in PMNs in defence against invading pathogens.
Reduced CCR4, interleukin‐13 and GATA‐3 up‐regulation in response to type 2 cytokines of cord blood T lymphocytes in infants at genetic risk of type 1 diabetes
Authors: Luopajärvi Kristiina , Skarsvik Susanne , Ilonen Jorma , Åkerblom Hans K. , Vaarala Outi
Published: May 2007

Aberrancies in T‐cell polarization including expression of chemokine receptors have been reported in human leucocyte antigen (HLA) class II associated autoimmune diseases, such as type 1 diabetes (T1D) and rheumatoid arthritis. We asked whether these aberrancies are present at birth in newborn infants carrying the HLA risk haplotypes for T1D. Sixty‐seven cord blood (CB) samples from infants were screened for T1D‐associated HLA risk genotypes (HLA‐DR4‐DQ8 and/or DR3‐DQ2 without protective alleles). CB lymphocytes were stimulated with phytohaemagglutinin in type 1 (interleukin (IL)‐12, anti‐IL4) or type 2 (IL‐4, anti‐IL12) cytokine environment for 6 days. The expression of chemokine and cytokine receptors on T cells was determined by flow cytometry, secretion of cytokines was analysed with enzyme‐linked immunosorbent assay, and transcription factors were analysed using real‐time reverse transcriptase–polymerase chain reaction. After culture of CB lymphocytes in type 2 cytokine environment newborn infants carrying DR4‐DQ8 haplotype (n = 18) showed reduced percentage of CD4 T cells expressing CCR4 (P = 0·009) and the level of CCR4 mRNA was decreased (P = 0·008). In addition, lower secretion of IL‐13 and expression of GATA‐3 in CB lymphocytes cultured in type 2 cytokine environment were found in the infants with DR4‐DQ8 haplotype (P = 0·020 and P = 0·004, respectively) in comparison to newborn infants without DR4‐DQ8 and DR3‐DQ2 haplotypes (n = 37). Poor in vitro induction of type 2 immune responses in newborn infants with DR4‐DQ8 haplotype suggests that the HLA genotype associated with risk of autoimmunity may affect the T cell polarization already at birth, which in turn may contribute to the risk for autoimmunity later in life.
The effect of condensation pressure on selected physical properties of mineral trioxide aggregate
Authors: Nekoofar M. H. , Adusei G. , Sheykhrezae M. S. , Hayes S. J. , Bryant S. T. , Dummer P. M. H.
Published: May 2007

Aim  To examine the effect of condensation pressure on surface hardness, microstructure and compressive strength of mineral trioxide aggregate (MTA).

Methodology  White ProRoot MTA (Dentsply Tulsa Dental, Johnson City, TN, USA) was mixed and packed into cylindrical polycarbonate tubes. Six groups each of 10 specimens were subjected to pressures of 0.06, 0.44, 1.68, 3.22, 4.46 and 8.88 MPa respectively. The surface hardness of each specimen was measured using Vickers microhardness. Cylindrical specimens of 4 mm in diameter and 6 mm in height were prepared in polycarbonate cylindrical moulds for testing the compressive strength. Five groups of 10 specimens were prepared using pressures of 0.06, 0.44, 1.68, 3.22 or 4.46 MPa. Data were subjected to one‐way anova. The microstructure was analysed using a scanning electron microscope (SEM) after sectioning specimens with a scalpel.

Result  A trend was observed for higher condensation pressures to produce lower surface hardness values. A condensation pressure of 8.88 MPa produced specimens with significantly lower values in terms of surface hardness than other groups (P < 0.001). A condensation pressure of 1.68 MPa conferred the maximum compressive strength; however, it was not statistically different. Higher condensation pressures resulted in fewer voids and microchannels when analysed with SEM. In specimens prepared with lower condensation pressures distinctive crystalline structures were observed. They tended to appear around microchannels.

Conclusion  Condensation pressure may affect the strength and hardness of MTA. Use of controlled condensation pressure in sample preparation for future studies is suggested.