bluuebunny/crossref_metadata_2025_split huggingface dataset:
New polymorphisms in the interleukin‐10 gene – relationships to myocardial infarction
Authors: Donger C. , Georges J‐L. , Nicaud V. , Morrison C. , Evans A. , Kee F. , Arveiler D. , Tiret L. , Cambien F. 
Published: March 2003

BackgroundInterleukin‐10 (IL‐10) is a cytokine with anti‐inflammatory and B‐cell‐stimulating activity. IL‐10 is expressed in human atherosclerotic plaques and recent studies have shown the involvement of IL‐10 in the atherosclerotic process. Therefore, we hypothesized that polymorphisms in the IL‐10 gene might be associated with a predisposition to coronary heart disease.Materials and methodsTo identify new polymorphisms in the human IL‐10 gene, the entire coding sequence and the 3′ flanking sequence of the gene were screened by polymerase chain reaction–single strand conformation polymorphism (PCR‐SSCR ) followed by sequencing. The polymorphisms identified, and three others which have been previously described in the promoter region of the IL‐10 gene (G‐1082A, C‐819T, C‐592A), were then investigated in the ECTIM Study, a large population‐based case–control study of myocardial infarction.ResultsFour new polymorphisms were identified: one in exon 1 (G+78/ex1A), which predicts a Glycine to Arginine change at position 15 in the putative signal peptide of the protein, two in the intron 3 (C+19/in3T, T+953/in3C) and one in the 3′ flanking region (C+117T). All the IL‐10 polymorphisms were in complete or nearly complete pairwise linkage disequilibrium. No case–control difference was found in genotype or allele frequencies for any of the polymorphisms.ConclusionsOur results suggest that IL‐10 polymorphisms are not associated with an increased risk of myocardial infarction.
The improvement of renal concentration capacity after surgery for primary hyperparathyroidism
Authors: Hedbäck G. , Abrahamsson K. , Odén A. 
Published: March 2003

Background Improvement of renal concentration capacity was long ago shown to occur after surgery for primary hyperparathyroidism (pHPT). Study of concentration capacity is of interest, as it was also shown to be a predictive factor for the risk of death in patients with pHPT, and it affected the risk of death independently of 33 other variables in multivariate analysis. Methods There were 98 patients with verified pHPT operated on in the years 1958–81, who had urine osmolality determinations performed both before and after surgery: 63 immediately after, and 35 with mean 3·9 years delay (SD = 1·8). Another seven patients with pHPT had urine osmolality determinations performed preoperatively only. Non‐parametric sign tests, regression analysis, and correlation tests were performed. Results Both patients with severe or moderate, and mild pHPT showed a substantial change of renal concentration capacity, with mean increase of 28·3% (SD = 28·4). The increase generally occurred soon after surgery. In eight out of 98 patients, there was no improvement. A relationship was found between improvement and preoperative peak serum calcium level. In seven out of seven patients followed, untreated for mean 5·3 years (SD = 3·2), there was a mean 15% (SD = 8·0) deterioration of renal concentration capacity. Conclusions The findings of this study add cause for surgery in patients with pHPT and give no reason for different treatment of severe, moderate or mild disease.
Why is soluble intercellular adhesion molecule‐1 related to cardiovascular mortality?
Authors: Becker A. , Van Hinsbergh V. W. M. , Jager A. , Kostense P. J. , Dekker J. M. , Nijpels G. , Heine R. J. , Bouter L. M. , Stehouwer C. D. A. 
Published: March 2003

Increased plasma levels of soluble adhesion molecules are associated with an increased risk of atherothrombosis. The pathophysiological mechanisms responsible for these associations are not known. The aim of the present study was to investigate the association of soluble intercellular adhesion molecule‐1 (sICAM‐1) concentration and risk of cardiovascular and all‐cause mortality among individuals with and without type 2 diabetes. In addition, we assessed potential pathophysiological mechanisms by which sICAM‐1 may promote mortality.Six hundred and thirty‐one subjects taken from a general population of the middle‐aged and elderly participated in this prospective cohort study. Baseline data collection was performed from 1989 to 1992; subjects were followed until 1 January 2000.Subjects who died had higher levels of sICAM‐1 than those who survived (506(164) vs. 477(162) ng mL−1, respectively). After adjustment for age, gender and glucose tolerance status, subjects with sICAM‐1 levels in the upper quartile (≥550 ng mL−1) had a relative risk of cardiovascular mortality of 2·05 (95% confidence interval, 1·10–3·81) compared to subjects with sICAM‐1 levels in the other quartiles. Further adjustment for classical cardiovascular risk factors or indicators of (sub)clinical atherosclerosis, endothelial dysfunction, inflammation and renal function did not materially alter this relative risk. A high sICAM‐1 level was more frequent in subjects with type 2 diabetes than in subjects with a normal glucose tolerance (33·3 vs. 17·8%).Individuals with a plasma concentration of sICAM‐1 higher than 550 ng mL−1 had a cardiovascular mortality risk that was twice that of individuals with a lower concentration. Classical cardiovascular risk factors (sub)clinical atherosclerosis, endothelial dysfunction and inflammation do not explain this excess risk.
Decreased trabecular bone biomechanical competence, apparent density, IGF‐II and IGFBP‐5 content in acromegaly
Authors: Ueland T. , Ebbesen E. N. , Thomsen J. S. , Mosekilde L. , Brixen K. , Flyvbjerg A. , Bollerslev J. 
Published: March 2003

AbstractBackground Earlier studies on the effect of excess growth hormone (GH) on trabecular bone have been conflicting. Since insulin‐like growth factors (IGFs) and their binding proteins (IGFBPs) in part mediate the effects of GH, the present study aimed to investigate trabecular bone composition of these growth factors in relation to biomechanical properties in acromegaly.Materials and methods Trabecular bone biomechanical competence (compression test), apparent density (peripheral quantitative computed tomography, pQCT), and bone matrix contents of calcium (HCl hydrolysis) and IGFs (guanidinium–HCl extraction) were measured in iliac crest biopsies from 13 patients with active acromegaly (two women and 11 men, aged 21–61 years) and 21 age‐ and sex‐matched controls (four women and 17 men, aged 23–64 years).Results Trabecular bone pQCT was reduced in acromegalic patients compared with controls (P = 0·005), as was biomechanical competence (P < 0·05 for all measures). These parameters were significantly positively correlated in both acromegalic patients and controls. The calcium content of trabecular bone was significantly increased in patients compared with controls. No significant differences were found in trabecular bone content of IGF‐I, IGFBP‐3, or osteocalcin. However, IGF‐II and IGFBP‐5 content was decreased (P < 0·001 and P < 0·05, respectively).Conclusions The present study demonstrates reduced trabecular biomechanical competence and apparent density in acromegaly, supporting previous observations of an unfavourable effect of chronic excess GH on the axial skeleton. Furthermore, we demonstrate decreased trabecular bone content of IGF‐II and IGFBP‐5 in these patients. However, we found no direct causal relationship between trabecular bone density and bone content of IGF‐system components.
Angiogenesis extent and expression of matrix metalloproteinase‐2 and ‐9 agree with progression of ovarian endometriomas
Authors: Ria R. , Loverro G. , Vacca A. , Ribatti D. , Cormio G. , Roccaro A. M. , Selvaggi L. 
Published: March 2003

AbstractBackground  Changes in angiogenesis and expression of extracellular matrix‐degrading enzymes have been substantiated in tumour changeover and progression.Methods  Tissues from 44 biopsies of stage III and IV ovarian endometriomas, and 10 biopsies of normal (control) endometrium were investigated immunohistochemically to count microvessels, and by in situ hybridization to assess the expression of mRNA of matrix metalloproteinase‐2 (MMP‐2) and MMP‐9. Implants of the tissues were investigated in the chick embryo chorioallantoic membrane (CAM) assay to determine their angiogenic capacity.Results  The endometriomas displayed significantly higher counts than normal endometria and the highest values were associated with the deepest invasion level (stage IV). Microvessels localized in close association with ectopic endometrial cells in the form of winding and arborized tubes, often dilated in microaneurysmatic segments. These were absent in normal endometrium. Expression of MMP‐2 and MMP‐9 mRNA, evaluated as percentages of positive biopsies and intensity of expression, was up‐regulated in endometriomas and more pronounced in stage IV. MMP‐2 and MMP‐9 mRNA were also expressed by host stromal cells, including microvascular endothelial cells, fibroblasts and macrophages, whereas the control endometrium showed very little expression of MMP‐2 mRNA in a few endothelial cells and no expression of MMP‐9 mRNA. Implants from stage IV endometrioma induced a more intense vasoproliferative response than those from stage III, while no vasoproliferative response was induced by the normal endometrium.Conclusion  These data suggest that angiogenesis and degradation of extracellular matrix occur together in endometriosis and are more pronounced in stage IV, and that endometriosis cells and some host stromal cell populations co‐operate in disease progression.
Inhibition of cell proliferation and fibronectin biosynthesis by Na ascorbate
Authors: Péterszegi G. , Dagonet F. B. , Labat‐Robert J. , Robert L. 
Published: March 2003

AbstractBackground The importance of ascorbate on the production of extracellular matrix proteins (as elastin and collagens) is now well documented, but no studies have been published concerning its effects on fibronectin biosynthesis. Fibronectin is important for cell attachment and for proliferation.Materials and methods The effects of Na ascorbate were investigated on cell attachment, proliferation, viability and fibronectin biosynthesis by human skin fibroblasts in vitro. Proliferation was followed by the monitoring of [3H]‐thymidine incorporation; viability by the MTT‐test, cell adherence by counting adherent and nonadherent cells and fibronectin biosynthesis by immunoprecipitation of biosynthetically labelled fibronectin.Results In the presence of ascorbate, the fibroblasts showed a biphasic growth pattern. At 500 µM ascorbate, [3H]‐thymidine incorporation was stimulated by 15% as compared to the controls. Higher concentrations gradually decreased proliferation up to 36% of the control value at 5 mM. These effects of ascorbate on DNA synthesis were followed to > 1·25 mM by a strong inhibition, cytotoxic effect and cell death. The non‐adherent cell count increased to 10% of the total population at 2·5 mM and to 31% at 5·0 mM ascorbate.Increasing concentrations of ascorbate resulted in a dose‐dependent decrease of fibronectin biosynthesis, both in the culture supernates and cell extracts. This inhibition mainly concerned cell membrane‐associated fibronectin.Superoxide‐dismutase or catalase could inhibit Na ascorbate‐induced cytotoxicity and partially re‐establish fibronectin biosynthesis. Desferrioxamine, ergothionein and vitamin E were inefficient.ConclusionsOur results indicate that ascorbate decreases fibronectin biosynthesis of cultured human skin fibroblasts, thereby producing cell detachment and decreased proliferation. This effect is mainly mediated by the reactive oxygen species and can be inhibited by superoxide‐dismutase and catalase.
Enhanced DNA damage‐induced p53 peptide phosphorylation and cell‐cycle arrest in Sjögren’s syndrome cells
Authors: Henriksson G. , Brant M. , Sallmyr A. , Fukushima S. , Manthorpe R. , Bredberg A. 
Published: March 2003

AbstractBackground Cells from primary Sjögren’s syndrome (SS) patients have been reported to show alterations in DNA repair and p53 expression. The DNA‐dependent protein kinase (DNA‐PK) autoantigen may be involved in both of these alterations in relation to cellular DNA damage responses. We conducted this study of cell‐cycle kinetics and p53 to find additional evidence for an abnormal stress response role in the pathogenesis of SS.Design DNA‐dependent protein kinase activity, p53 peptide phosphorylation and p53 protein levels were determined in gamma‐irradiated long‐term T lymphocyte cultures. Cell‐cycle progression of peripheral blood mononuclear cells was analysed with flow cytometry.Results No significant differences in the DNA‐PK activities or p53 protein levels appeared between the SS patients and the healthy individuals. However, patients with the SS hallmark Ro/SS‐A and La/SS‐B autoantibodies showed enhancement of both p53 peptide phosphorylation (P = 0·036) and G1 cell‐cycle arrest (P = 0·015) in response to gamma radiation.Conclusions Sjögren’s syndrome cells express an enhanced G1 checkpoint function which may be mediated partly by p53 phosphorylation, suggesting that an abnormal stress response in SS is of relevance for the development of this autoimmune disease.
Tauroursodeoxycholic acid mobilizes α‐PKC after uptake in human HepG2 hepatoma cells
Authors: Glasova Helena , Berghaus Thomas M. , Kullak‐Ublick Gerd A. , Paumgartner Gustav , Beuers Ulrich 
Published: March 2003

AbstractBackground Tauroursodeoxycholic acid (TUDCA) may exert anticholestatic effects via Ca++‐ and α‐protein kinase C (α‐PKC)‐dependent apical vesicular insertion of canalicular transporters in cholestatic hepatocytes (Hepatology 2001; 33: 1206–16). Tauroursodeoxycholic acid is mainly taken up into liver cells by Na+‐taurocholate cotransporting polypeptide (Ntcp). Tauroursodeoxycholic acid selectively translocates α‐PKC, a key mediator of regulated exocytosis, to hepatocellular membranes. It is unclear whether TUDCA exerts its effects on α‐PKC after carrier‐mediated uptake into liver cells or by interaction with extracellular/membraneous structures.Materials and methods Human hepatoblastoma HepG2 cells lacking Ntcp were stably transfected with pcDNA3·1/Ntcp or sham‐transfected with pcDNA3·1 [+]. Distribution of α‐PKC was studied using a Western blotting technique. Uptake of [3H]taurocholic acid (TCA) was determined radiochemically.Results [3H]taurocholic acid uptake was approximately 180‐fold higher in Ntcp‐transfected than in sham‐transfected cells. Phorbol 12‐myristate 13‐acetate (1 µmol L−1; positive control) increased membrane binding of α‐PKC by 34% in Ntcp‐transfected and by 37% in sham‐transfected cells. Tauroursodeoxycholic acid (10 µmol L−1) increased membrane‐associated α‐PKC by 19% in Ntcp‐transfected, but not in sham‐transfected cells (−13%). Taurocholic acid (10 µmol L−1) did not affect the distribution of α‐PKC.Conclusion Carrier‐mediated uptake is a prerequisite for TUDCA‐induced translocation of α‐PKC to hepatocellular membranes.
Therapy of circadian rhythm disorders in chronic fatigue syndrome: no symptomatic improvement with melatonin or phototherapy
Authors: Williams G. , Waterhouse J. , Mugarza J. , Minors D. , Hayden K. 
Published: March 2003

AbstractBackground Patients with chronic fatigue syndrome (CFS) show evidence of circadian rhythm disturbances. We aimed to determine whether CFS symptoms were alleviated by melatonin and bright‐light phototherapy, which have been shown to improve circadian rhythm disorders and fatigue in jet‐lag and shift workers.Design Thirty patients with unexplained fatigue for > 6 months were initially assessed using placebo and then received melatonin (5 mg in the evening) and phototherapy (2500 Lux for 1 h in the morning), each for 12 weeks in random order separated by a washout period. Principal symptoms of CFS were measured by visual analogue scales, the Shortform (SF‐36) Health Survey, Mental Fatigue Inventory and Hospital Anxiety and Depression Scale. We also determined the circadian rhythm of body temperature, timing of the onset of melatonin secretion, and the relationship between these.Results Neither intervention showed any significant effect on any of the principal symptoms or on general measures of physical or mental health. Compared with placebo, neither body temperature rhythm nor onset of melatonin secretion was significantly altered by either treatment, except for a slight advance of temperature phase (0·8 h; P = 0·04) with phototherapy.Conclusion Melatonin and bright‐light phototherapy appear ineffective in CFS. Both treatments are being prescribed for CFS sufferers by medical and alternative practitioners. Their unregulated use should be prohibited unless, or until, clear benefits are convincingly demonstrated.
Longitudinal evolution of HIV‐1‐associated lipodystrophy is correlated to serum cortisol:DHEA ratio and IFN‐α
Authors: Christeff N. , De Truchis P. , Melchior J.‐C. , Perronne C. , Gougeon M.‐L. 
Published: March 2003

AbstractBackground We have previously shown that lipid alterations in HIV‐1‐associated lipodystrophy (LD) are correlated with decreased serum dehydroepiandosterone (DHEA) and increased cortisol:DHEA ratio and IFN‐α levels.Objective To evaluate in a longitudinal study whether steroid and cytokine modifications are associated with the evolution of physical changes and lipid alterations associated with LD.Methods Thirty‐four HIV‐1‐positive men were followed during 32·5 ± 4·0 months and tested at four time‐points. The patients were subdivided into five groups according to physical changes and anthropometric measurements: LD‐negative, initially LD‐negative becoming LD‐positive, LD‐positive unchanged, aggravated or improved. Serum lipids, apolipoproteins, adrenal steroids and cytokines were measured and compared with baseline values.Results (1) LD aggravation is associated with persistent elevated lipids, a decrease in serum DHEA, an increase in cortisol:DHEA ratio and persistent high levels of IFN‐α. (2) LD improvement is associated with normalization of serum lipids, an increase in serum DHEA leading to normalization in cortisol:DHEA ratio, and normalization of IFN‐α levels. (3) In LD‐positive men evolution of VLDL cholesterol is negatively correlated with DHEA (r = −0·56, P < 0·01) and positively with cortisol:DHEA ratio (r = 0·62, P < 0·004) and with IFN‐α (r = 0·57, P < 0·01). (4) The switch to LD is associated with a decrease in serum DHEA. (5) Patients who remained LD‐negative maintained normal lipids, elevated cortisol and DHEA, and normal cortisol:DHEA ratio and normal levels of IFN‐α.Conclusions This study indicates that cortisol:DHEA ratio and serum IFN‐α levels are closely associated with clinical evolution and atherogenic lipid alterations in LD.
Haemochromatosis mutations and ferritin in myocardial infarction: a case‐control study
Authors: Claeys D. , Walting M. , Julmy F. , Wuillemin W. A. , Meyer B. J. 
Published: March 2003

AbstractBackground  Iron accumulation may contribute to coronary heart disease by catalysing free radical formation and promoting oxidation of low‐density lipoprotein cholesterol. Epidemiological studies of iron status and coronary heart disease are conflicting.Design  To test whether genetic haemochromatosis is associated with myocardial infarction, we determined the prevalence of three mutations in the HFE gene (Cys282Tyr, His63Asp and Ser65Cys) in a 2 : 1 case‐control study including 177 patients who survived an acute myocardial infarction and 89 controls. Genotypes were determined by PCR amplification of genomic DNA followed by restriction enzyme digestion. We also studied the relationship between plasma ferritin and myocardial infarction.Results  The carrier frequencies of these three mutations were not statistically different among patients and controls (Cys282Tyr: 12·4 vs. 10·1%; His63Asp: 26·5 vs. 31·5%; Ser65Cys: 2·8 vs. 1·1%). Mean ferritin levels were elevated among patients (176 ± 155 µg L−1) compared with controls (131 ± 106 µg L−1, P = 0·015). Subjects with plasma ferritin concentrations of 300 µg L−1 or more had a 2·9‐fold (95% CI: 1·2–7·3, P = 0·02) unadjusted risk for a myocardial infarction compared with those with normal levels. In a univariate analysis, ferritin was significantly associated with myocardial infarction. Upon multiple regression analysis adjusting for smoking, hypertension, diabetes, body‐mass index and total cholesterol, significance was no longer present.ConclusionsNo direct association was found between genetic haemochromatosis and myocardial infarction among Swiss whites. Raised ferritin levels among patients suggest a role of increased iron stores in myocardial infarction, but iron overload was not an independent risk factor for Swiss coronary heart disease patients.
Novel intronic variants of MICB (MHC class I chain‐related gene B)
Authors: Fischer G. , Argüello J. R. , Pérez‐Rodríguez M. , Cox S. T. , McWhinnie A. , Marsh S. G. E. , Madrigal J. A. 
Published: March 2003

AbstractWe report an eight‐nucleotide duplication in intron 4 of the MICB allele 01021, which was found in samples from different ethnic backgrounds and in association with several HLA‐B alleles. We suggest that this new MICB allele is evolutionarily older than HLA‐B alleles.
A novel polymorphism in the human interleukin‐13 (IL‐13) promoter
Authors: Laundy G. J. , Spink C. F. , Keen L. J. , Wood N. A. P. , Bidwell J. L. 
Published: March 2003

AbstractUsing PCR–SSCP and automated nucleotide sequencing we have identified a novel single nucleotide C → T polymorphism in the human IL‐13 promoter, at position —1055 relative to the transcription start site. Allele frequency analysis in a population of normal cord blood donors indicated frequencies of 0.833 (C) and 0.167 (T).
Geographical differences within Finland in the frequency of HLA‐DQ genotypes associated with Type 1 diabetes susceptibility
Authors: Ilonen J. , Reijonen H. , Green A. , Reunanen A. , Knip M. , Simell O. , Åkerblom H. K. ,   the Childhood Diabetes in Finland Study Group
Published: March 2003

AbstractGeographical variations in the HLA‐DQ genotypes associated with risk for type 1 diabetes were evaluated in Finland. Samples of 280 diabetic children diagnosed in Turku (south‐west of the country) and 405 in Oulu (north of the country) were studied as well as a series of 14 096 and 10 016 newborns collected from the same hospitals. There were no major differences in the risk or protection conferred by various HLA‐DQB1 genotypes between south‐western and northern parts of the country when genotypes of children with type 1 diabetes from these two centres were compared with those of newborns, representing the background populations. However, the distribution of various genotypes was different, both in diabetic children and in newborns, when compared between the two regions (P < 0.0001, χ2 test). These differences reflected the allele frequencies in newborn cohorts in which HLA‐DQB1*02 and DQB1*0301 were found more often in Turku and DQB1*0302 more often in Oulu (P < 0.0001 for all differences). Similar types of differences were detected when children who were diagnosed as having diabetes during the national ‘Childhood Diabetes in Finland’ (DiMe) study between the years 1986–1989 were compared according to their residence. The observed differences in genotype and allele frequencies demonstrate the heterogeneity for HLA alleles even in a population that is generally regarded as highly homogeneous. These differences also affect the sensitivity and efficiency of the screening programme used for identifying infants with genetic susceptibility to IDDM in the ongoing Finnish Diabetes Prediction and Prevention Study.