bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory mechanisms of resveratrol in platelet activation: pivotal roles of p38 MAPK and NO/cyclic GMP
Authors: Shen Ming Y. , Hsiao George , Liu Chang L. , Fong Tsorng H. , Lin Kuang H. , Chou Duen S. , Sheu Joen R. 
Published: September 2007

SummaryResveratrol has been reported to have antiplatelet activity; however, the detailed mechanisms have not yet been resolved. This study aimed to systematically examine the detailed mechanisms of resveratrol in the prevention of platelet activation in vitro and in vivo. Resveratrol (0·05–0·25 μmol/l) showed stronger inhibition of platelet aggregation stimulated by collagen (1 μg/ml) than other agonists. Resveratrol (0·15 and 0·25 μmol/l) inhibited collagen‐induced platelet activation accompanied by [Ca+2]i mobilization, thromboxane A2 (TxA2) formation, phosphoinositide breakdown, and protein kinase C (PKC) activation. Resveratrol markedly increased levels of NO/cyclic guanosine monophosphate (GMP), and cyclic GMP‐induced vasodilator‐stimulated phosphoprotein phosphorylation. Resveratrol markedly inhibited p38 mitogen‐activated protein kinase (MAPK) but not Jun N‐terminal kinase or extracellular signal‐regulated kinase‐2 phosphorylation in washed platelets. Resveratrol‐reduced hydroxyl radical (OH−) formation in the electron spin resonance study. In an in vivo study, resveratrol (5 mg/kg) significantly prolonged platelet plug formation of mice. In conclusion, the main findings of this study suggest that the inhibitory effects of resveratrol possibly involve (i) inhibition of the p38 MAPK‐cytosolic phospholipase A2‐arachidonic acid‐TxA2‐[Ca+2]i cascade and (ii) activation of NO/cyclic GMP, resulting in inhibition of phospholipase C and/or PKC activation. Resveratrol is likely to exert significant protective effects in thromboembolic‐related disorders by inhibiting platelet aggregation.
Clinical characteristics and treatment outcome of infants with non‐Hodgkin lymphoma
Authors: Mann Georg , Attarbaschi Andishe , Burkhardt Birgit , Niggli Felix , Klapper Wolfram , Ludwig Wolf‐Dieter , Schrappe Martin , Zimmermann Martin , Gadner Helmut , Reiter Alfred ,   The Berlin‐Frankfurt‐Münster Group
Published: September 2007

SummaryNon‐Hodgkin lymphoma (NHL) is rarely observed during infancy and data on its incidence, characteristics and outcome are scarce. The present study aimed to assess the prevalence, clinical presentation and treatment results of all infants who were diagnosed with NHL between October 1986 and December 2002 among 2084 patients treated according to the NHL‐BFM (Berlin‐Frankfurt‐Münster) multicentre trials 86, 90 and 95. We identified 20 (1%) infants with NHL including five with T‐cell lymphoblastic lymphoma (T‐cell LBL), seven with precursor B‐cell LBL (pB‐cell LBL), two with a mature Burkitt neoplasm, five with anaplastic large cell lymphoma (ALCL) and one with peripheral T‐cell lymphoma (PTCL). The PTCL patient, 3/7 pB‐cell LBL and 1/5 ALCL patients relapsed. One patient each from the T‐cell LBL and Burkitt lymphoma groups suffered from a second malignancy and one patient each with ALCL and Burkitt leukaemia died from treatment‐related toxicity. The 5‐year event‐free survival rate was 53 ± 12% for the 20 cases. This study has provided preliminary evidence that infants with NHL have a dismal prognosis and showed that infant NHL differed to lymphomas in older patients with respect to the distribution of gender, histopathologic subtypes as well as the ratio of T‐ to pB‐cell LBL and the frequency of relapses of pB‐cell LBL.
Association of autoimmune disease‐related gene polymorphisms with chronic graft‐versus‐host disease
Authors: Shimada Masako , Onizuka Makoto , Machida Shinichiro , Suzuki Rikio , Kojima Minoru , Miyamura Koichi , Kodera Yoshihisa , Inoko Hidetoshi , Ando Kiyoshi 
Published: September 2007

SummaryChronic graft‐versus‐host disease (GVHD) is the most common cause of poor outcomes after haematopoietic stem cell transplantation (HSCT), while the pathophysiology of chronic GVHD remains poorly understood. As both chronic GVHD and autoimmune disease share clinical features, we speculated that autoimmune disease‐related genes might be candidate chronic GVHD‐related genes. Recent large‐scale cohort studies showed that Fc receptor‐like 3 gene (FCRL3) single nucleotide polymorphism (SNP) and peptidylarginine deiminases citrullinating enzymes 4 gene (PADI4) haplotype were associated with autoimmune disease. The present study investigated the association between polymorphisms of these two genes and the incidence of chronic GVHD. We analysed 123 cases of Japanese human leucocyte antigen‐matched sibling recipients and their donors who underwent HSCT. Although PADI4, which is the rheumatoid arthritis‐specific related gene, was not associated with the occurrence of chronic GVHD, the recipient FCRL3‐169C/C genotype was significantly less frequent in chronic GVHD patients than in those without chronic GVHD (P = 0·0086). There was no relationship between FCRL3 polymorphism and acute GVHD. As FCRL3 is expressed by B cells and might have an important role in immunoregulation, this significant protective genetic effect raises the question of whether FCRL3 might also be involved in the pathogenesis of chronic GVHD.
Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake
Authors: Mian Caterina , Barollo Susi , Pennelli Gianmaria , Pavan Nicodemo , Rugge Massimo , Pelizzo Maria Rosa , Mazzarotto Renzo , Casara Dario , Nacamulli Davide , Mantero Franco , Opocher Giuseppe , Busnardo Benedetto , Girelli Maria Elisa 
Published: September 2007

SummaryObjective  Papillary thyroid cancers (PTCs) with no iodine uptake have an aggressive behaviour and a poor prognosis. The aim of our study was to characterize, at molecular level, a subset of PTC with no 131 iodine (131I) uptake.Design and methods  Forty‐eight cancer tissues were divided into three groups: Group 1, 28 primary cancers; Group 2, 7 recurrences capable of trapping 131I; and Group 3, 13 recurrences incapable of trapping 131I. mRNA levels of thyroid genes (sodium/iodide symporter NIS, thyroglobulin, thyroperoxidase and pendrin) and glycolytic metabolism genes (GLUT‐1, hexokinase I and II) and BRAF mutations were evaluated in the different groups.Results  Cancers with no 131I uptake had slightly reduced NIS, significantly reduced thyroglobulin (P < 0·01), thyroperoxidase (P = 0·01) and pendrin (P = 0·03) and significantly increased GLUT‐1 (P = 0·01) gene expression levels; and a high frequency of BRAF mutations (77%). BRAFV600E mutation, in both primary and metastatic thyroid cancers, is associated with a marked drop in thyroperoxidase (29‐fold) and pendrin (20‐fold) expression and a considerable increase (five‐fold) in GLUT‐1 expression.Conclusions  (1) The loss of 131I uptake in recurrences depends not only on a decrease in NIS gene, but possibly on a reduction in the molecules regulating its intracellular metabolism; (2) the high GLUT‐1 gene expression supports the use of positron emission tomography with specific tracers in clinical management of such cancers; and (3) BRAFV600E point mutations may lead to less differentiated phenotypes, suggesting a worse prognosis.
Frequent mutations of β‐catenin gene in sporadic secreting adrenocortical adenomas*
Authors: Tadjine Mimi , Lampron Antoine , Ouadi Lydia , Bourdeau Isabelle 
Published: September 2007

SummaryObjective  Molecular alterations remain largely unknown in most sporadic adrenocortical tumours and hyperplasias. In our previous work, we demonstrated the differential expression of several Wnt/β‐catenin signalling‐related genes implicated in ACTH‐independent macronodular adrenal hyperplasias (AIMAH). To better understand the role of Wnt/β‐catenin signalling in adrenocortical tumours, we performed mutational analysis of the β‐catenin gene.Methods  We studied 53 human adrenocortical samples (33 adenomas, 4 carcinomas, 13 AIMAH, 3 ACTH‐dependent adrenal hyperplasias) and the human adrenocortical cancer cell line NCI‐H295R. All samples were screened for somatic mutations in exons 3 and 5 of the β‐catenin gene. Eleven and six samples were analysed for β‐catenin protein expression by Western blotting and immunohistochemistry, respectively.Results  No mutations were detected in adrenocortical carcinomas, AIMAH and ACTH‐dependent hyperplasias. Genetic alterations were found in 5 (15%) out of 33 adenomas: three cortisol‐secreting adenomas, one aldosterone‐secreting adenoma and one nonfunctional adenoma. Two‐point mutations occurred at serine residues of codons 37 and 45 (S37C and S45F). The remaining three tumours contained deletions of 6, 55 and 271 bp. H295R cells carry an activating S45P mutation. Western blot analysis of samples with 55‐ and 271‐bp deletions showed an additional shorter and more intense band representing an accumulation of the mutated form of β‐catenin protein. In addition, cytoplasmic and/or nuclear accumulation of β‐catenin was observed in mutated adenomas by immunohistochemistry.Conclusions  Activating mutations of exon 3 of the β‐catenin gene are frequent in adrenocortical adenomas, and further characterization of the Wnt/β‐catenin signalling pathway should lead to a better understanding of adrenal tumourigenesis.
Hypovitaminosis D and parathyroid hormone response in the elderly: effects on bone turnover and mortality
Authors: Chen Jian Sheng , Sambrook Philip N. , March Lyn , Cameron Ian D. , Cumming Robert G. , Simpson Judy M. , Seibel Markus J. 
Published: September 2007

SummaryObjective  To investigate whether absence of secondary hyperparathyroidism in the presence of hypovitaminosis D has altered bone turnover, fracture risk and mortality.Design  A prospective cohort study.Patients  A total of 1280 older men and women living in residential care facilities.Measurements  We measured baseline serum 25‐hydroxyvitamin D (25OHD), serum intact PTH, serum amino‐terminal propeptide of type I collagen (PINP) and serum carboxy‐terminal telopeptide of type I collagen (CTX‐I). Deaths and fractures were recorded prospectively.Results  Hypovitaminosis D (25OHD < 39 nmol/l) and absence of secondary hyperparathyroidism (PTH > 7·0 pmol/l) in the presence of hypovitaminosis D were common in this sample with a prevalence of 77·5% and 53·3%, respectively. In the presence of hypovitaminosis D, residents showing a hyperparathyroid response (n = 406) had significantly higher serum bone turnover markers than individuals with serum PTH levels ≤ 7·0 pmol/l (termed ‘low vitamin D, normal PTH’, n = 463). After adjusting for risk factors, mortality was significantly higher in the secondary hyperparathyroidism group than in the ‘low vitamin D, normal PTH’ group [hazard ratio (HR) = 1·35, 95% confidence interval (CI) 1·12–1·64; P = 0·002]. All residents with serum PTH levels ≤ 7·0 pmol/l (n = 603) were similar with regard to both bone turnover and mortality, independent of their actual vitamin D status.Conclusion  Absence of secondary hyperparathyroidism in the presence of hypovitaminosis D appears to be common in the frail elderly and is associated with longer survival, similar to that observed in vitamin D‐replete elderly subjects.
Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight
Authors: Reinehr Thomas , De Sousa Gideon , Roth Christian L. 
Published: September 2007

SummaryObjectives  Obestatin and ghrelin, which are derived from the same gene, are observed to have opposite effects on weight status. The aims of this study were to compare obestatin concentrations in obese and normal‐weight children and to analyse the effect of weight loss on obestatin and ghrelin levels.Methods  We examined anthropometrical markers and fasting serum obestatin, ghrelin, leptin, glucose and insulin concentrations in 44 obese children (mean age 11·2 years) before and after participating in a 1‐year outpatient obesity intervention programme based on a high‐carbohydrate, fat‐reduced diet and increased physical activity. Additionally, total ghrelin, obestatin and leptin levels were determined in 22 normal‐weight healthy children of similar age, gender and pubertal stage.Results  Obestatin and leptin concentrations were significantly (P < 0·001) higher and ghrelin concentrations were significantly (P < 0·001) lower in obese children compared to nonobese children. In contrast to the 13 children without weight loss, substantial weight loss in 31 children led to a significant (P = 0·007) increase in obestatin and to a significant (P < 0·05) decrease in leptin and insulin concentrations, while ghrelin concentrations did not change significantly. Children with substantial weight loss demonstrated significantly (P = 0·009) lower obestatin and a tendency (P = 0·064) to higher ghrelin concentrations at baseline. Changes in insulin were not related to changes in ghrelin or obestatin.Conclusion  The increase in obestatin and the decrease in ghrelin in obese children point towards an adaptation process of weight status. Weight reduction due to a long‐term lifestyle intervention resulted in an increase in obestatin levels.
Does a highly sensitive thyroglobulin (Tg) assay change the clinical management of low‐risk patients with thyroid cancer with Tg on T4 < 1 ng/ml determined by traditional assays?
Authors: Rosario P. W. , Purisch S. 
Published: September 2007

SummaryObjective  To evaluate a highly sensitive thyroglobulin (Tg) assay [functional sensitivity (FS): 0·1 ng/ml] (Tg‐ICMA) in low‐risk patients with known Tg on T4 ≤ 1 ng/ml measured by a traditional assay (FS: 1 ng/ml) (Tg‐IRMA).Methods  Tg‐ICMA was measured in serum samples stored at –70 °C. Samples were obtained 6 months or more after total thyroidectomy and remnant ablation with 131I, during L‐T4 therapy (TSH < 0·4 mIU/l). All patients had well‐differentiated and completely resected tumours, no ectopic uptake on post‐therapy whole‐body scans and were considered to be at low risk for recurrence. On the occasion of collection and retesting for this study, Tg‐IRMA was ≤ 1 ng/ml in all samples and no antibody interference was observed.Results  Tg‐ICMA ≤ 0·1 ng/ml was observed in 130/178 (73%) patients and recurrence was diagnosed in only 1/130 (0·8%). Tg‐IRMA measured after L‐T4 withdrawal was > 1 ng/ml in 5/130 (3·8%) patients. Forty‐eight (27%) patients had Tg‐ICMA > 0·1 ng/ml (0·12–1·6 ng/ml) and recurrence was diagnosed in 5/48 (10·5%). Tg‐IRMA measured after L‐T4 withdrawal was > 1 ng/ml in 20/48 (41·6%) patients. A negative predictive value of 100% was achieved with Tg‐ICMA on T4 ≤ 0·1 ng/ml combined with neck ultrasonography (US) or with stimulated Tg‐IRMA ≤ 1 ng/ml.Conclusions  Patients at low risk for recurrence with undetectable Tg on T4 measured by a highly sensitive assay (FS: 0·1 ng/ml) in the absence of antibody interference and with a negative sensitive neck US do not need to be submitted to Tg stimulation. Recurrence is rare in these cases and only a minority of patients convert to stimulated Tg > 1–2 ng/ml.
Analysis of gross deletions in the MEN1 gene in patients with multiple endocrine neoplasia type 1
Authors: Owens Martina , Ellard Sian , Vaidya Bijay 
Published: September 2007

SummaryBackground  Mutation analysis with direct DNA sequencing is commonly used for the molecular diagnosis of multiple endocrine neoplasia type 1 (MEN1). However, a significant number of patients, despite clinical features of MEN1, do not show MEN1 mutations on direct DNA sequencing. Some of these patients may have gross gene deletions not detected by direct DNA sequencing or mutations in the noncoding regions of the gene not examined routinely.Objective  To determine the prevalence of gross deletions in MEN1 in a large cohort of MEN1 patients.Patients and methods  During 1997–2006, we screened MEN1 mutations by direct DNA sequencing in 368 probands referred to our diagnostic molecular genetic laboratory. Of these, 101 probands (23 familial, 78 sporadic) fulfilled the clinical criteria for MEN1 (presence of at least two of the parathyroid, pancreatic or pituitary tumours) but were negative for mutations on DNA sequencing. Their DNA samples were examined for gross deletions of one or more exons of MEN1 by using multiple ligation‐dependent probe amplification (MLPA) and long‐range polymerase chain reaction (PCR) amplification. We also sequenced the minimal promoter region of MEN1 for mutations in the familial cases.Results  We identified a gross deletion involving exons 5 and 6 of MEN1 in one proband (prevalence rate 1%). The sequencing of the minimal promoter region in the familial cases revealed no mutations.Conclusion  Gross deletion in the MEN1 gene is an uncommon cause of MEN1 and should be tested for in patients with a high clinical suspicion but without mutations on direct DNA sequencing.
Effects of the progestagen‐only contraceptive implant Implanon® on cardiovascular risk factors
Authors: Merki‐Feld Gabriele S. , Imthurn Bruno , Seifert Burkhardt 
Published: September 2007

SummaryObjective  Epidemiological studies on the cardiovascular risk of progestagen‐only contraceptives are rare. With the present study we aimed to investigate the effect of the low‐dose etonogestrel‐releasing contraceptive implant Implanon® on cardiovascular risk factors, including markers of inflammation.Design  Longitudinal study.Setting  Family planning centre of a University Hospital.Subjects  Thirty‐six healthy, nonsmoking women with regular cycles (n = 18 controls without hormonal contraception; n = 18 cases requesting the insertion of Implanon®).Measurements  Blood samples for the determination of C‐reactive protein (CRP), nitric oxide (NO), sex hormones and plasma lipids were taken in the early follicular phase of the cycle in both groups. A second sample was taken 12 weeks after Implanon insertion or in the controls during the early follicular phase of cycle 4.Results  Implanon treatment caused a 36% decrease in CRP (P < 0·06) and a significant decrease in high density lipoprotein (HDL) (P < 0·007), low density lipoprotein (LDL) (P < 0·001), cholesterol (P < 0·001), testosterone (P < 0·05) and SHBG (P < 0·002). Levels of NO, oestradiol and progesterone were not affected in either group. The cholesterol/HDL ratio did not change in Implanon carriers. There was a significant correlation between the cardiovascular risk factors CRP, cholesterol/HDL ratio and NO.Conclusion  The progestagen‐only implant Implanon does not exert a negative effect on the cardiovascular risk factors CRP, cholesterol/HDL ratio and NO. These results suggest that the use of a progestagen‐only contraception does not increase cardiovascular risk factors in healthy young women.
High prevalence of cardiac hypertophy without detectable signs of fibrosis in patients with untreated active acromegaly: anin vivostudy using magnetic resonance imaging
Authors: Bogazzi Fausto , Lombardi Massimo , Strata Elisabetta , Aquaro Giovanni , Di Bello Vitantonio , Cosci Chiara , Sardella Chiara , Talini Enrica , Martino Enio 
Published: September 2007

SummaryObjective Left ventricular (LV) hypertrophy and myocardial fibrosis are considered the main pathological features of acromegalic cardiomyopathy. The aim of the study was to evaluate the proportion of LV hypertrophy and the presence of fibrosis in acromegalic cardiomyopathyin vivousing cardiac magnetic resonance (CMR).Design and patients Fourteen consecutive patients (eight women, mean age 46 ± 10 years) with untreated active acromegaly were submitted to two‐dimensional (2D) colour Doppler and integrated backscatter (IBS) echocardiography and CMR.Measurements LV volume, mass and wall thickness and myocardial tissue characterization (IBS and CMR).Results On echocardiography: mean LV mass (LVM) and LVM index (LVMi) were 209 ± 48 g and 110 ± 24 g/m2, respectively; hypertrophy was revealed in five patients (36%); abnormal diastolic function [evaluated by isovolumic relaxation time (IVRT) or early (E) to late or atrial (A) peak velocities (E/A ratio)] was found in four patients (29%). Systolic function evaluated by measuring LV ejection fraction (LVEF) was normal (mean 72 ± 12%) in all patients. Six patients (43%) had increased IBS (mean 57·4 ± 6·2%). On CMR: mean LVM and LVMi were 151 ± 17 g and 76 ± 9 g/m2, respectively; 10 patients (72%) had LV hypertrophy. Contrastographic delayed hyperenhancement was absent in all patients; on the contrary, mild enhancement was revealed in one patient. Systolic function was normal in all patients (LVEF 67 ± 11%). LVMi was not related to serum IGF‐1 concentrations or the estimated duration of disease.Conclusions CMR is considered to be the gold standard for evaluating cardiac hypertrophy, fibrosis and systolic function. Using CMR, 72% patients with untreated active acromegaly had LV hypertrophy, which was only detected in 36% patients by echocardiography. However, cardiac fibrosis was absent in all patients irrespective of the estimated duration of disease. Although a very small increase in collagen content (as suggested by increased cardiac reflectivity at IBS), not detectable by CMR, could not be ruled out, it is unlikely that it would significantly affect cardiac function.
Seasonal dynamics of carbon and nitrogen pools and fluxes under continuous arable and ley‐arable rotations in a temperate environment
Authors: Murphy D. V. , Stockdale E. A. , Poulton P. R. , Willison T. W. , Goulding K. W. T. 
Published: September 2007

SummaryImproved understanding of the seasonal dynamics of C and N cycling in soils, and the main controls on these fluctuations, is needed to improve management strategies and to better match soil N supply to crop N demand. Although the C and N cycles in soil are usually considered to be closely linked, few data exist where both C and N pools and gross N fluxes have been measured seasonally. Here we present measurements of inorganic N, extracted soluble organic N, microbial biomass C and N, gross N fluxes and CO2 production from soil collected under wheat in a ley‐arable and continuous arable rotation within a long‐term experiment. The amounts of inorganic N and extracted soluble organic N were similar (range 5–35 kg N ha−1; 0–23 cm) but had different seasonal patterns: whilst inorganic N declined during wheat growth, extracted soluble organic N peaked after cultivation and also during maximal stem elongation. The microbial biomass was significantly larger in the ley‐arable (964 kg C ha−1; 0–23 cm) than the continuous arable rotation (518 kg C ha−1; 0–23 cm) but with no clear seasonal pattern. In contrast, CO2 produced from soil and gross N mineralization showed strong seasonality linked to soil temperature and moisture content. Normalization of soil CO2 production and gross N mineralization with respect to these environmental regulators enabled us to study the underlying influence of the incorporation of fresh plant material into soil on these processes. The average normalized gross rates of N mineralized during the growing season were 1.74 and 2.55 kg N ha−1 nday−1 in continuous arable and ley‐arable rotations respectively. Production rates (gross N mineralization, gross nitrification) were similar in both land uses and matched rates of NH4+ and NO3− consumption, resulting in periods of net N mineralization and immobilization. There was no simple relationship between soil CO2 production and gross N mineralization, which we attributed to changes in the C : N ratio of the mineralizing pool(s).