bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brachial artery pulse pressure and common carotid artery diameter: mutually independent associations with mortality in subjects with a recent history of impaired glucose tolerance
Authors: Van Dijk R. A. J. M. , Dekker J. M. , Nijpels G. , Heine R. J. , Bouter L. M. , Stehouwer C. D. A. 
Published: March 2003

Background Decreased large artery function, as reflected by increased brachial artery pulse pressure and increased carotid artery diameter and stiffness, may contribute to the increased mortality risk that is observed in subjects with impaired glucose tolerance. We therefore investigated the association between brachial artery pulse pressure and carotid artery diameter and stiffness, which are estimates of central artery stiffness and arterial remodelling, respectively, and mortality in subjects with a recent history of impaired glucose tolerance.Design A prospective, population‐based cohort study. We measured brachial artery pulse pressure by oscillometric blood pressure measurements, and common carotid artery diameter and distensibility and compliance coefficients by ultrasound in 140 subjects with a recent history of impaired glucose tolerance. During a median 6·6‐year follow‐up, 16 subjects died.Results Brachial artery pulse pressure and common carotid artery diameter were positively related to all‐cause mortality [hazard ratios per standard deviation, 1·7 (1·2–2·5) and 2·1 (1·3–3·3), respectively]. Results were similar after adjustment for gender, age, waist‐to‐hip ratio, body mass index, total cholesterol concentration, pre‐existent cardiovascular disease, and hypertension, and after additional mutual adjustment. Common carotid artery distensibility and compliance coefficients were not statistically significantly associated with mortality.Conclusions Among subjects with a recent history of impaired glucose tolerance, brachial artery pulse pressure and common carotid artery diameter are independently associated with mortality risk. Stiffness of the central arteries may explain the association between pulse pressure and mortality risk. The association between carotid diameter and mortality risk is more likely to reflect arterial remodelling in response to atherosclerosis than that in response to increased local stiffness.
Quantitative, phenotypic, and functional evaluation of basophils in myelodysplastic syndromes
Authors: Füreder W. , Schernthaner G.‐H. , Ghannadan M. , Hauswirth A. , Sperr W. R. , Semper H. , Majlesi Y. , Zwirner J. , Götze O. , Bühring H.‐J. , Lechner K. , Valent P. 
Published: March 2003

Background The myelodysplastic syndromes (MDS) are a group of clonal haematological disorders characterized by cytopenia(s), reduced differentiation‐capacity of myeloid cells, and impaired leukocyte function. However, little is known so far about basophil granulocytes in MDS.Design We have compared the numbers, phenotype and function of basophils in MDS patients with those in healthy subjects. A total numer of 23 patients with MDS (refractory anaemia, n = 8; refractory anaemia with ringsideroblasts, n = 7; refractory anaemia with excess of blasts/refractory anaemia with excess of blasts in transformation, n = 8) and 20 healthy donors were included.Results The numbers of blood basophils in MDS patients (34·6 ± 62·9 μL−1) was lower compared to healthy controls (58·6 ± 64·9 μL−1). Correspondingly, whole blood histamine levels were lower in MDS patients (MDS 34·1 ± 29·1 ng mL−1 vs. normal donors 72·0 ± 36·9 ng mL−1). Like ‘normal’ basophils, basophils in MDS expressed interleukin‐3 receptor α (CD123), E‐NPP3 (CD203c), CR1 (CD35), CR3 (CD11b), CR4 (CD11c), membrane co‐factor protein (CD46), decay‐accelerating factor (CD55) and membrane attack complex inhibitory factor (CD59), as well as receptors for C3a, C5a (CD88), and IgE. Recombinant human (rh) C5a and anti‐IgE induced significant release of histamine from basophils in both groups of donors without significant differences between MDS and healthy controls.Conclusions The absolute numbers of basophils in MDS patients are lower than in normal donors. However, basophils in MDS do not differ from their ‘normal counterparts’ in terms of complement receptor expression, IgE‐receptor expression, or functional responses to respective ligands.
Expression of hepatocyte growth factor, keratinocyte growth factor and their receptors in experimental chronic pancreatitis
Authors: Otte J‐M. , Schwenger M. , Brunke G. , Sparmann G. , Emmrich J. , Schmitz F. , Fölsch U. R. , Herzig K.‐H. 
Published: March 2003

Background Hepatocyte (HGF) and Keratinocyte growth factors (KGF) are key factors of tissue organization and regeneration. These peptide growth factors and their receptors c‐met and keratinocyte growth factor receptor (KGFR) are overexpressed in pancreatic cancer.Aim Expression and localization of ligands and receptors were investigated during the development of experimental chronic pancreatitis.Methods Chronic pancreatitis was induced in rats by intravenous injection of dibutyltin dichloride. One to 60 days after treatment, the expression of growth factors and receptors was analysed by competitive polymerase chain reaction, Western blot analysis and immunohistochemistry.Results HGF mRNA expression increased (10‐fold) until days 7–14 followed by a decrease to control level. Expression of c‐met mRNA constantly increased (15‐fold). KGF and KGFR mRNA expression were increased after 14–28 days (5‐fold) and then returned to control levels. mRNA expression patterns correlated with changes in the protein expression, whereas protein levels of KGF remained unchanged. Ligands were localized in mesenchymal cells and their receptors on epithelial cells.Conclusions The significant increase of HGF and c‐met expression suggests an essential role of this growth factor in the morphological changes during the development of chronic pancreatitis. Changes in the expression of KGF and KGFR are less pronounced.
Re‐adaptation of the gastroduodenal mucosa to DNA synthesis during protracted stress
Authors: Rubio C. A. , Sveander M. , Befrits R. 
Published: March 2003

Background Previous study showed that under the influence of protracted physical stress, the DNA synthesis (DS) of the gastroduodenal mucosa rises, the highest peak being reached at 4 weeks. At 8 stress weeks, the DS decreases to values similar to those recorded at the beginning of the experiment. The possibility that this DS adaptation (DSA) could be maintained beyond 8 weeks in animals allowed to subsequent resting (stress‐free) weeks, was now explored.Methods Sixty‐five rats were investigated. Sixty rats were transported to the stress laboratory. Thirty were water plunged and 30 sham handled once a day, 5 days a week, for 8 weeks. After 8 stress weeks, groups of 5 animals were allowed to rest for one, two, three and four weeks, ending with single water plunging or sham handling. All 65 animals received ip injection of 3H‐thymidine before they were sacrificed. The ratio radioactive DNA/total DNA reflected the DS of the stomach and duodenum.Results DSA was achieved at 8 stress weeks (stomach). The DS in the stomach of stressed rats had significantly increased at 10 weeks (P < 0·05), but at 12 weeks it had decreased to 8 weeks values. The DS in the duodenum of stressed rats had significantly increased at 9, 10 and 11 weeks (P < 0·05), but at 12 weeks DS values had decreased to those of 8 weeks.Conclusions The DSA at 8 stress weeks had not prevailed because the DS increased considerably in the following weeks. At 9–11 weeks, DS values had significantly increased (P < 0·05) in stressed rats, but at 12 weeks a DS re‐adaptation (DSRA) had occurred. Thus, it took 8 weeks to achieve DSA (stomach), but only 4 weeks to accomplish DSRA. Animals experienced sham handling as an stressor (milder) as it also induced DS re‐adjustments in the gastroduodenal mucosa. Autoradiography showed that the labelling in DNA synthesizing cells was limited almost exclusively to the mucosal layer. The model described may prove of value to studies aimed at abating the disparate fluctuations of DNA synthesis in the gastroduodenal mucosa during the various phases of protracted stress.
Helicobacter pylori masks differences in homocysteine plasma levels between controls and type 2 diabetic patients
Authors: Cenerelli S. , Bonazzi P. , Galeazzi R. , Testa I. , Bonfigli A. R. , Sirolla C. , Giunta S. , Galeazzi L. , Fumelli D. , Testa R. 
Published: March 2003

AbstractBackground Data in the literature have not clarified whether type 2 diabetes mellitus affects homocysteine plasma levels. Different variables able to influence homocysteine could be the cause of these controversial findings. An important but neglected confounding factor is Helicobacter pylori, which has been demonstrated to be a cause of elevated levels of homocysteine and which is prevalent in the Caucasian population, ranging from 30 to 40% incidence. Starting from these findings we wanted to verify whether differences in homocysteine levels exist between a type 2 diabetic population and a control group, taking into account the presence/absence of Helicobacter pylori.Design The study was carried out on a group of uncomplicated and normotensive type 2 diabetic patients (n = 30, 55·7 ± 9·7 years) and on a control group (n = 43, 51·2 ± 11·3 years). On these subjects we evaluated: main parameters of glyco‐ and lipo‐metabolic balance, presence of Helicobacter pylori by 13C Urea Breath Test, plasma homocysteine, vitamin B12, folate and genetic polymorphism of methylenetetrahydrofolate reductase.Results Evaluating the two groups as a whole, significant differences in homocysteine were found when considering Helicobacter pylori presence/absence (14·0 ± 6·5 vs. 10·6 ± 4·7 µmol L−1, respectively, P < 0·01) without differences of vitamins and the genetic polymorphism of methylenetetrahydrofolate reductase. The positive interaction found among Helicobacter pylori, diabetes and homocysteine (P = 0·03) taking into account all the other evaluated confounding factors, demonstrates that a significant difference in homocysteine plasma levels exists between diabetics and controls (Helicobacter pylori‐negative: diabetics 12·5 ± 5·6 µmol L−1, controls 9·4 ± 3·8 µmol L−1; Helicobacter pylori‐positive: diabetics 13·6 ± 5·8 µmol L−1, controls 14·3 ± 7·0 µmol L−1).Conclusions Type 2 diabetes seems to induce per se higher levels of homocysteine, which appears to be one of the factors responsible for the increased risk of vascular damage.
Complement activating antibodies against the human 60 kDa heat shock protein as a new independent family risk factor of coronary heart disease
Authors: Veres A. , Szamosi T. , Ablonczy M. , Szamosi T. , Singh M. , Karádi I. , Romics , L. , Füst G. , Prohászka Z. 
Published: March 2003

AbstractBackground Several groups have reported high levels of antibodies against 60 kDa heat shock proteins (hsp) associated with coronary heart disease.Methods and results Complement activating (CA) antihsp60 autoantibodies were measured by the AtheroRisk kit (CardioPath Ltd, Alloa, UK), in parallel with IgG antibodies to human hsp60 and mycobacterial hsp65 by ELISA in 32 healthy children (18 boys, 14 girls, 11·8 ± 4·0 years). At least one of the parents of these children had a history of myocardial infarction before 55 years of age (high family risk (HFR) group). The control group consisted of 63 healthy children (31 boys, 32 girls, 9·0 ± 3·6 years) without known family history of coronary heart disease (CHD), hypertension, and diabetes mellitus. Concentrations of CA antihsp60 antibodies were significantly (P = 0·021) higher in the HFR group than in the control group. Also in the HFR group, significantly (P = 0·004) lower high‐density lipoprotein cholesterol (HDL‐C)‐cholesterol (measured enzymatically) and significantly (P = 0·020) higher low‐density lipoprotein cholesterol (LDL‐C)‐cholesterol levels (calculated by the Friedewald formula) were observed when compared with the controls. The difference in the CA antihsp60 antibody levels between the HFR and control groups remained significant even after adjustments for age, smoking, HDL‐cholesterol, LDL‐cholesterol levels, and white blood cell count. Children with high (in the highest quartile) CA antihsp60 antibody levels compared with those with normal levels of these antibodies also had adjusted odds ratios (OR) of 9·80 (2·15–44·58, P = 0·003), indicating high family risk. No significant difference in the IgG antihsp antibody levels was observed.Conclusions These findings indicate that high levels of CA autoantibodies against hsp60 can be considered to be a novel family risk factor of CHD, independent of HDL‐ and LDL‐cholesterol levels.
Effects of hormone replacement therapy on blood platelets
Authors: Thijs A. , Van Baal W. M. , Van Der Mooren M. J. , Kenemans P. , Dräger A. M. , Huijgens P. C. , Stehouwer C. D. A. 
Published: March 2003

AbstractBackground Hormone replacement therapy (HRT) increases the risk of cardiovascular morbidity in postmenopausal women under certain circumstances. Part of this effect may be the result of the influence of HRT on blood platelets. We studied the effect of short‐term oral hormone replacement therapy (unopposed oestradiol or sequentially combined oestradiol and trimegestone or dydrogesterone) on platelet activation parameters in healthy postmenopausal women.Design We designed a prospective, randomised, placebo‐controlled 12‐week study. Sixty healthy, normotensive, nonhysterectomised, postmenopausal women received daily micronised oestradiol (E2) 2 mg (n = 16), or 2 mg E2 daily sequentially combined with either trimegestone 0·5 mg daily (n = 14) or dydrogesterone 10 mg daily (n = 14), or placebo (n = 16). Data on platelet activation were collected at baseline and after 12 weeks of treatment using flow cytometry.Results Twelve weeks of treatment with combined HRT was associated with an increase in platelet activation parameters P‐selectin and glycoprotein 53 (by 17% and 14%, respectively, P = 0·04 vs. the placebo group for both comparisons), suggesting alpha granule and lysosome degranulation. E2 replacement therapy was associated with an increase in P‐selectin labelling by 22% (P = 0·04 vs. the placebo group).Conclusion Short‐term treatment with oestradiol or combined HRT increases the amount of circulating activated platelets as measured by flow cytometry. This could be a mechanism by which short‐term HRT might increase the risk of thrombosis.
Effect of nicotine replacement and quitting smoking on circulating adhesion molecule profiles (sICAM‐1, sCD44v5, sCD44v6)
Authors: Palmer R. M. , Stapleton J. A. , Sutherland G. , Coward P. Y. , Wilson R. F. , Scott D. A. 
Published: March 2003

AbstractBackground Soluble ICAM‐1 (sICAM‐1; sCD54), sCD44v5 and sCD44v6 are circulating adhesion molecules, with immunomodulatory potential, that have been frequently attributed diagnostic, prognostic and aetiological significance in a number of inflammatory and malignant diseases. We have previously shown that systemic concentrations of these molecules are increased significantly in tobacco smokers, but reduce to within normal levels at 12 months following successful quitting.Materials and methods We have been able to extend these observations by measuring levels before and 4, 8, 22 and 52 weeks after smoking cessation in subjects receiving high‐dose nicotine replacement therapy (25 mg of nicotine; n= 34) or placebo patches (n = 34) for 26 weeks. Smoking cessation was confirmed by regular measurement of expired‐air CO levels and by plasma cotinine analysis.Results Plasma sICAM‐1, sCD44v5 and sCD44v6 concentrations all declined rapidly within 4 weeks of smoking cessation (P < 0·001 for all declines). Additionally, no differences were observed between those using nicotine replacement and those who were not for sICAM‐1, sCD44v5, or sCD44v6.Conclusions The recovery in smoking‐associated adhesion molecule profiles represents an almost immediate beneficial effect of smoking cessation. Nicotine replacement therapy is an effective aid to quitting and does not affect these recoveries. The elevated levels of these important risk factors in smokers (sICAM‐1, sCD44v5 and sCD44v6) are linked to noxious element(s) in tobacco smoke other than nicotine or nicotine metabolites.
Red blood cell antioxidant and iron status in alcoholic and nonalcoholic cirrhosis
Authors: Fiorelli G. , De Feo T. M. , Duca L. , Tavazzi D. , Nava I. , Fargion S. , Cappellini M. D. 
Published: March 2003

AbstractBackground Iron overload has been reported in alcoholic liver cirrhosis but it remains to be established whether iron is involved in inducing oxidative damage to erythrocytes in alcoholic cirrhosis. The aim of this study was to assess oxidative damage and red cell indicators of antioxidant defences in alcoholics with mild‐to‐severe liver cirrhosis, taking into account the iron status.Materials and methods Twenty‐nine patients with alcoholic liver cirrhosis (AC) and 27 with nonalcoholic cirrhosis (NAC) were studied. Serum lipid peroxides (LPO) were assayed by a colourimetric method. Serum‐free malonyldialdehyde (MDA) was assayed by selected ion monitoring in positive chemical ionization; serum 4‐hydroxy‐2(E)‐nonenal (4‐HNE) was determined by a colorimetric method. Reduced (GSH) and oxidized glutathione (GSSG), adenine and pyridine cofactors were assayed in whole blood extracts by HPLC. Hexose‐monophosphate shunt (HMPS), glycolytic pathway (EMP) and antioxidant enzyme activities were determined by standard methods. Iron status was evaluated by standard clinical chemistry and by histological grading of liver iron. Nontransferrin‐bound iron (NTBI) was measured in serum by HPLC.Results GSH progressively decreased with increasing severity of liver involvement in AC and NAC. MDA, 4‐HNE and NTBI were significantly higher in AC serum. Stimulation of red cell HMPS and reducing potential, in terms of NADPH production, were more pronounced in AC.ConclusionsThese results suggest that NTBI is more important than the decrease of antioxidant defences in inducing lipid peroxidation. NTBI may play a catalytic role in free radical reactions in the presence of cellular reductants such as NADPH.
Inhibition of endogenous pancreatic enzyme secretion by oral pancreatic enzyme treatment
Authors: Walkowiak J. , Witmanowski H. , Strzykala K. , Bychowiec B. , Songin T. , Borski K. , Herzig K.‐H. 
Published: March 2003

AbstractBackground  The existence of a feedback mechanism for exocrine pancreatic secretion in humans is controversial. Exclusion of proteases from the duodenum stimulates exocrine pancreatic secretion. Conversely, addition of exogenous enzymes could reduce the enzyme secretion. Further investigation of the feedback mechanism should be performed under the most physiological conditions. In the present study we investigated exocrine pancreatic function by measuring fecal enzyme output in healthy volunteers consuming a normal diet, before and during a time course of exogenous pancreatic enzyme supplementation.Material and methods  Twenty‐five healthy subjects (HS) were given two different doses (30 and 60 FIP proteases kg−1 d−1) divided by the number of meals. In all subjects, fecal elastase‐1 (E1) concentrations and chymotrypsin (ChT) activities were measured without and with enzyme supplements after 7 days of treatment. In eight subjects, E1 concentrations and ChT activities were measured daily for 10 consecutive days. The subjects were given a dose regimen of 100 FIP proteases kg−1 d−1 (divided by the number of meals) for the first 7 days.Results  Oral pancreatic treatment dose‐dependently inhibited endogenous pancreatic secretion measured with the use of E1 concentrations. In both regimen groups, the differences were statistically significant. The exogenous enzymes, which interfere with colorimetric method for ChT, dose‐dependently increased ChT output. However, only the higher dose resulted in a statistically significant difference. In the subgroup of eight HS, time‐dependent changes of fecal enzyme output occurred with a decrease of E1 concentrations and an increase of ChT activity from the second up to eighth or ninth day of the experiment.Conclusion  Exogenous applied pancreatic enzymes, dose‐ and time‐dependently inhibited endogenous pancreatic secretion. The obtained results strongly support the existence of a protease mediated feedback mechanism in humans.
Phylogenetic analysis of primate MIC (PERB11) sequences suggests that the representation of the gene family differs in different primates: comparison of MIC (PERB11) and C4
Authors: Cattley S. K. , Longman N. , Dawkins R. L. , Gaudieri S. , Kulski J. K. , Leelayuwat C. 
Published: March 2003

Duplication of segments within the MHC has led to numerous multicopy families such as class I, class II, C4 and MIC (PERB11). Different copy numbers between haplotypes and species may be explained by the extent of duplication and subsequent deletion. There are at least five copies of MIC (PERB11) in humans, but MICA (PERB11.1) appears to have been deleted from the chimpanzee.By comparing the sequences of primates (chimpanzee, gorilla, gibbon, orang‐utan, pygmy chimpanzee, Patas monkey, Aethiops and baboon) we conclude that the gorilla has a copy of PERB11.1, whereas the baboon and Patas possess MICD (PERB11.4) and/or MICE (PERB11.5) rather than MICA (PERB11.1). These findings indicate that the primate MHC is more plastic than has been appreciated.
Inverted ratio of m‐fas/s‐fas expression in early onset pauciarticular juvenile chronic arthritis
Authors: Haas J.‐P. , Frank C. , Haefner R. , Herrmann M. , Späth H. , Ruder H. 
Published: March 2003

AbstractThe expression of m‐fas/apo1 (CD95) and its soluble form (s‐fas) was studied in patients with early onset pauciarticular (n = 23) and systemic juvenile chronic arthritis (n = 7). RNA was prepared from peripheral blood of patients and 22 healthy controls and from 23 samples derived from the synovial fluid of JCA patients. The ratio of m‐fas/s‐fas transcripts was calculated by densitometry of fas‐specific RT‐PCR products. An inverted ratio of m‐fas/s‐fas transcripts was found in PBMC and mononuclear cells from the joints of early onset pauciarticular JCA patients. The m‐fas/s‐fas ratios were similar in PBMC and mononuclear cells from synovial fluid. PBMC from patients with a systemic JCA showed the same m‐fas/s‐fas ratio as healthy controls, with an inverted ratio of both transcripts in cells from the synovial fluid. The data indicate a role of Fas/Apo1 regulated apoptosis in EOPA‐JCA which is not limited to the affected joints.
Human platelet antigens: typing by PCR using sequence‐specific primers and their distribution in blood donors resident in Wales
Authors: Sellers J. , Thompson J. , Guttridge M. G. , Darke C. 
Published: March 2003

AbstractWe developed and validated HPA‐1 to HPA‐6 typing by PCR–SSP using a combination of established, modified and newly designed sequence‐specific primers. We confirmed that the PCR primer mixtures functioned under the same PCR conditions as our standard HLA‐A, ‐B, ‐C, ‐DR, ‐DQ PCR–SSP typing system. This allows concurrent testing for both HPA and HLA specificities and is therefore the system of choice for both clinical and large‐scale blood donor panel HPA and HLA typing by PCR–SSP. Test validation included typing a population of blood donors living in Wales. These HPA frequencies were consistent with those of other European Caucasoid populations. HPA‐4b and ‐6b were absent and HPA‐5b, which shows some frequency variation, had a phenotype frequency of 18.9% (allele frequency 0.0973), being close to that of the Dutch (19.7%) and Austrian (20.4%) populations and almost twice that found in Finns (10.0%). HPA genotype frequencies showed a good fit to Hardy–Weinberg equilibrium, further supporting the validity of our typing method.
Rare polymorphisms in the promoter regions of the human interleukin‐12 p35 and interleukin‐12 p40 subunit genes
Authors: Pravica Vera , Brogan Iain J. , Hutchinson Ian V. 
Published: March 2003

AbstractWe have described two rare, single‐nucleotide polymorphisms within the promoter regions of the IL‐12 p35 and p40 subunit genes. Transitions C to T at position −916 from the transcription start of the IL‐12 p35 gene and G to T at position −1287 in the IL‐12 p40 gene were observed.