bluuebunny/crossref_metadata_2025_split huggingface dataset:
[Ca2+]i rise at in vitro maturation in bovine cumulus–oocyte complexes
Authors: Silvestre Francesco , Fissore Rafael A. , Tosti Elisabetta , Boni Raffaele 
Published: March 2012

AbstractAn intracellular calcium ([Ca2+]i) rise has been described in cumulus–oocyte complexes (COCs) following luteinizing hormone (LH) exposure. Together with cAMP, Ca2+ is a candidate signal for resumption of meiosis. Here, we analyzed if the most common hormones involved in oocyte maturation can induce the same Ca2+ signal. In addition, we characterized the source of this signal. Immature, in vitro‐matured, and roscovitine‐meiotically arrested COCs were loaded with Fluo‐4 AM, stimulated with hormones/growth factors, and tested for [Ca2+]i variations in cumulus cells. Reagents known to inhibit or stimulate [Ca2+]i rises were used to characterize these [Ca2+]i dynamics. Finally, expression of LH receptors (LHRs) in COCs was analyzed by immunofluorescence. In immature COCs, follicle‐stimulating hormone (FSH) elicited a single [Ca2+]i rise that was higher than those induced by LH and growth hormone (GH), whereas epithelial growth factor failed to induce any changes in [Ca2+]i. The [Ca2+]i rise induced by FSH was higher in immature COCs; was reduced in roscovitine‐arrested, immature COCs; and was negligible in gonadotropin‐induced, in vitro‐matured COCs. In the case of spontaneous‐ and GH‐matured COCs, however, FSH stimulation caused a lower [Ca2+]i rise. The hormone‐induced [Ca2+]i rise was due to: (i) external Ca2+ entry; (ii) intercellular communication; and (iii) intracellular Ca2+ stores. Immunofluorescence revealed that LHRs were expressed throughout the cumulus cells. The above results show that: (i) gonadotropins and GH cause a [Ca2+]i rise in cumulus cells; (ii) this [Ca2+]i rise results from extra‐, inter‐, and intra‐cellular cumulative Ca2+ fluxes; and (iii) LHRs are distributed on either outer or inner cumulus cells. Mol. Reprod. Dev. 79:369–379, 2012. © 2012 Wiley Periodicals, Inc.
The effects of school poverty on adolescents' sexual health knowledge
Authors: Atkins Robert , Sulik Michael J. , Hart Daniel , Ayres Cynthia , Read Nichole 
Published: March 2012

AbstractUsing National Longitudinal Study of Adolescent Health data, hierarchical linear modeling was conducted to estimate the association of school poverty concentration to the sexual health knowledge of 6,718 adolescents. Controlling for individual socio‐economic status, school poverty had modest negative effects on sexual health knowledge. Although not directly associated with sexual health knowledge, after controlling for demographic characteristics, school poverty interactions showed that sexual health knowledge was associated with higher grade point average (GPA) and age. The combination of low GPA and high‐levels of school poverty was especially detrimental for students' sexual health knowledge. There are differences in the sexual health knowledge of adolescents attending low poverty and high poverty schools that can be attributed to the school environment. © 2012 Wiley Periodicals, Inc. Res Nurs Health 35:231–241, 2012
Coordinated expression of REG4 and aldehyde dehydrogenase 1 regulating tumourigenic capacity of diffuse‐type gastric carcinoma‐initiating cells is inhibited by TGF‐β
Authors: Katsuno Yoko , Ehata Shogo , Yashiro Masakazu , Yanagihara Kazuyoshi , Hirakawa Kosei , Miyazono Kohei 
Published: March 2012

AbstractAldehyde dehydrogenase 1 (ALDH1) has been shown to serve as a marker for cancer‐initiating cells (CICs), but little is known about the regulation of the CIC functions of ALDH1+ cancer cells. We isolated ALDH1+ cells from human diffuse‐type gastric carcinoma cells and characterized these cells using an Aldefluor assay. ALDH1+ cells constituted 5–8% of the human diffuse‐type gastric carcinoma cells, OCUM‐2MLN and HSC‐39; were more tumourigenic than ALDH1− cells; and were able to self‐renew and generate heterogeneous cell populations. Using gene expression microarray analyses, we identified REG4 (regenerating islet‐derived family, member 4) as one of the genes up‐regulated in ALDH1+ cells, and thus as a novel marker for ALDH1+ tumour cells. Induced expression of REG4 enhanced the colony‐forming ability of OCUM‐2MLN cells, while knockdown of REG4 inhibited the tumourigenic potential of ALDH1+ cells. We further found that TGF‐β signalling reduces the expression of ALDH1 and REG4, and the size of the ALDH1+ cell population. In human diffuse‐type gastric carcinoma tissues, the expression of ALDH1 and REG4 correlated with each other, as assessed by immunohistochemistry, and ALDH1 expression correlated inversely with Smad3 phosphorylation as a measure of TGF‐β signalling. These findings illustrate that, in diffuse‐type gastric carcinoma, REG4 is up‐regulated in ALDH1+ CICs, and that the increased tumourigenic ability of ALDH1+ cells depends on REG4. Moreover, TGF‐β down‐regulates ALDH1 and REG4 expression, which correlates with a reduction in CIC population size and tumourigenicity. Targeting REG4 in ALDH1+ CICs may provide a novel strategy in the treatment of diffuse‐type gastric carcinoma. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Tissue‐based proteomics reveals FXYD3, S100A11 and GSTM3 as novel markers for regional lymph node metastasis in colon cancer
Authors: Meding Stephan , Balluff Benjamin , Elsner Mareike , Schöne Cédrik , Rauser Sandra , Nitsche Ulrich , Maak Matthias , Schäfer Alexander , Hauck Stefanie M , Ueffing Marius , Langer Rupert , Höfler Heinz , Friess Helmut , Rosenberg Robert , Walch Axel 
Published: March 2012

AbstractRegional lymph node metastasis negatively affects prognosis in colon cancer patients. The molecular processes leading to regional lymph node metastasis are only partially understood and proteomic markers for metastasis are still scarce. Therefore, a tissue‐based proteomic approach was undertaken for identifying proteins associated with regional lymph node metastasis. Two complementary tissue‐based proteomic methods have been employed. MALDI imaging was used for identifying small proteins (≤25 kDa) in situ and label‐free quantitative proteomics was used for identifying larger proteins. A tissue cohort comprising primary colon tumours without metastasis (UICC II, pN0, n = 21) and with lymph node metastasis (UICC III, pN2, n = 33) was analysed. Subsequent validation of identified proteins was done by immunohistochemical staining on an independent tissue cohort consisting of primary colon tumour specimens (n = 168). MALDI imaging yielded ten discriminating m/z species, and label‐free quantitative proteomics 28 proteins. Two MALDI imaging‐derived candidate proteins (FXYD3 and S100A11) and one from the label‐free quantitative proteomics (GSTM3) were validated on the independent tissue cohort. All three markers correlated significantly with regional lymph node metastasis: FXYD3 (p = 0.0110), S100A11 (p = 0.0071), and GSTM3 (p = 0.0173). FXYD3 and S100A11 were more highly expressed in UICC II patient tumour tissues. GSTM3 was more highly expressed in UICC III patient tumour tissues. By our tissue‐based proteomic approach, we could identify a large panel of proteins which are associated with regional lymph node metastasis and which have not been described so far. Here we show that novel markers for regional lymph metastasis can be identified by MALDI imaging or label‐free quantitative proteomics and subsequently validated on an independent tissue cohort. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Genetic identification and functional validation of FcγRIV as key molecule in autoantibody‐induced tissue injury
Authors: Kasperkiewicz Michael , Nimmerjahn Falk , Wende Sabina , Hirose Misa , Iwata Hiroaki , Jonkman Marcel F , Samavedam Unni , Gupta Yask , Möller Steffen , Rentz Ellen , Hellberg Lars , Kalies Kathrin , Yu Xinhua , Schmidt Enno , Häsler Robert , Laskay Tamás , Westermann Jürgen , Köhl Jörg , Zillikens Detlef , Ludwig Ralf J 
Published: March 2012

AbstractAutoantibody‐mediated diseases are clinically heterogeneous and often fail conventional therapeutic strategies. Gene expression profiling has helped to identify new molecular pathways in these diseases, although their potential as treatment targets largely remains to be functionally validated. Based on weighted gene co‐expression network analysis, we determined the transcriptional network in experimental epidermolysis bullosa acquisita (EBA), a paradigm of an antibody‐mediated organ‐specific autoimmune disease characterized by autoantibodies directed against type VII collagen. We identified 33 distinct and differentially expressed modules, including Fcγ receptor (FcγR) IV and components of the neutrophil‐associated enzyme system in autoantibody transfer‐induced EBA. Validation experiments, including functional analysis, demonstrated that FcγRIV expression on neutrophils crucially contributes to autoantibody‐induced tissue injury in the transfer model of EBA. Mice lacking the common γ‐chain of activating FcγRs, deficient in FcγRIV or treated with FcγRIV function blocking antibody, but not mice deficient in FcγRI, FcγRIIB, FcγRIII or both FcγRI and FcγRIII, were effectively protected from EBA. Skin disease was restored in γ‐chain‐deficient mice locally reconstituted with neutrophils from wild‐type, but not from γ‐chain‐deficient, mice. Our findings both genetically and functionally identify a novel disease‐related molecule, FcγRIV, in an autoantibody‐mediated disorder, which may be of importance for the development of novel targeted therapies. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
TGFBR2 but not SPP1 genotype modulates osteopontin expression in Duchenne muscular dystrophy muscle
Authors: Piva Luisa , Gavassini Bruno F , Bello Luca , Fanin Marina , Soraru Gianni , Barp Andrea , Ermani Mario , Angelini Corrado , Hoffman Eric P , Pegoraro Elena 
Published: March 2012

AbstractA polymorphism (rs28357094) in the promoter region of the SPP1 gene coding for osteopontin (OPN) is a strong determinant of disease severity in Duchenne muscular dystrophy (DMD). The rare G allele of rs28357094 alters gene promoter function and reduces mRNA expression in transfected HeLa cells. To dissect the molecular mechanisms of increased disease severity associated with the G allele, we characterized SPP1 mRNA and protein in DMD muscle biopsies of patients with defined rs28357094 genotype. We did not find significant differences in osteopontin mRNA or protein expression between patients carrying the T (ancestral allele) or TG/GG genotypes at rs28357094. The G allele was significantly associated with reduced CD4+ and CD68+ cells on patient muscle biopsy. We also quantified transforming growth factor‐β (TGFB) and TGFB receptor‐2 (TGFBR2) mRNA in DMD muscle biopsies, given the ability of TGFB and TGFBR2 to activate SPP1 promoter region and their role in DMD pathogenesis. The amount of TGFB and TGFBR2 mRNA did not predict the amount of SPP1 mRNA or protein, while a polymorphism in the TGFBR2 gene (rs4522809) was found to be a strong predictor of SPP1 mRNA level. Our findings suggest that OPN mediates inflammatory changes in DMD and that TGFB signalling has a role in the complex regulation of osteopontin expression. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Chemical castration and anti‐androgens induce differential gene expression in prostate cancer
Authors: Lehmusvaara Saara , Erkkilä Timo , Urbanucci Alfonso , Waltering Kati , Seppälä Janne , Larjo Antti , Tuominen Vilppu J , Isola Jorma , Kujala Paula , Lähdesmäki Harri , Kaipia Antti , Tammela Teuvo LJ , Visakorpi Tapio 
Published: March 2012

AbstractEndocrine therapy by castration or anti‐androgens is the gold standard treatment for advanced prostate cancer. Although it has been used for decades, the molecular consequences of androgen deprivation are incompletely known and biomarkers of its resistance are lacking. In this study, we studied the molecular mechanisms of hormonal therapy by comparing the effect of bicalutamide (anti‐androgen), goserelin (GnRH agonist) and no therapy, followed by radical prostatectomy. For this purpose, 28 men were randomly assigned to treatment groups. Freshly frozen specimens were used for gene expression profiling for all known protein‐coding genes. An in silico Bayesian modelling tool was used to assess cancer‐specific gene expression from heterogeneous tissue specimens. The expression of 128 genes was > two‐fold reduced by the treatments. Only 16% of the altered genes were common in both treatment groups. Of the 128 genes, only 24 were directly androgen‐regulated genes, according to re‐analysis of previous data on gene expression, androgen receptor‐binding sites and histone modifications in prostate cancer cell line models. The tumours containing TMPRSS2–ERG fusion showed higher gene expression of genes related to proliferation compared to the fusion‐negative tumours in untreated cases. Interestingly, endocrine therapy reduced the expression of one‐half of these genes and thus diminished the differences between the fusion‐positive and ‐negative samples. This study reports the significantly different effects of an anti‐androgen and a GnRH agonist on gene expression in prostate cancer cells. TMPRSS2‐ERG fusion seems to bring many proliferation‐related genes under androgen regulation. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Abdominal aortic calcification in young adult survivors of childhood acute lymphoblastic leukemia: Results from the St. Jude Lifetime Cohort study
Authors: Gurney James G. , Ojha Rohit P. , Ness Kirsten K. , Huang Sujuan , Sharma Shelly , Robison Leslie L. , Hudson Melissa M. , Kaste Sue C. 
Published: March 2012

AbstractAbdominal aortic calcification (AAC), metabolic syndrome, and low bone mineral density (BMD) are risk factors for atherosclerotic disease and cardiovascular morbidity. We evaluated AAC in 662 adult survivors of childhood ALL (median age 31 years). AAC was present in 10% of subjects, metabolic syndrome in 36%, and low BMD in 29%. The adjusted odds ratio (OR) for AAC among women with metabolic syndrome was 2.3 (95% CL = 1.0, 4.3). The adjusted OR for AAC in men with low BMD was 3.1 (95% CL = 1.3, 7.3). A substantial proportion of adult survivors of childhood ALL have AAC and/or metabolic syndrome, suggestive of early atherosclerotic disease. Pediatr Blood Cancer 2012; 59: 1307–1309. © 2012 Wiley Periodicals, Inc.
Quantitative description of the morphology and ossification center in the axial skeleton of 20‐week gestation formalin‐fixed human fetuses using magnetic resonance images
Authors: Chabert Steren , Villalobos Manuel , Ulloa Patricia , Salas Rodrigo , Tejos Cristian , San Martin Sebastian , Pereda Jaime 
Published: March 2012

ABSTRACTObjectivesHuman tissues are usually studied using a series of two‐dimensional visualizations of in vivo or cutout specimens. However, there is no precise anatomical description of some of the processes of human fetal development. The purpose of our study is to develop a quantitative description of the normal axial skeleton by means of high‐resolution three‐dimensional magnetic resonance (MR) images, collected from six normal 20‐week‐old human fetuses fixed in formaldehyde.MethodsFetuses were collected after spontaneous abortion and subsequently fixed with formalin. They were imaged using a 1.5 T MR scanner with an isotropic spatial resolution of 200 µm. The correct tissue discrimination between ossified and cartilaginous bones was confirmed by comparing the images achieved by MR scans and computerized axial tomographies. The vertebral column was segmented out from each image using a specially developed semi‐automatic algorithm.ResultsVertebral body dimensions and inter‐vertebral distances were larger in the lumbar region, in agreement with the beginning of the ossification process from the thoracolumbar region toward the sacral and cephalic ends.ConclusionIn this article, we demonstrate the feasibility of using MR images to study the ossification process in formalin‐fixed fetal tissues. A quantitative description of the ossification centers of vertebral bodies and arches is presented. © 2012 John Wiley & Sons, Ltd.
Body stalk anomaly: adverse maternal outcomes in a series of 21 cases
Authors: Costa Maria Laura Botelho , Couto Egle , Furlan Erica , Zaccaria Renata , Andrade Kleber , Barini Ricardo , Nomura Marcelo Luís 
Published: March 2012

ABSTRACTObjectiveTo evaluate the demographic characteristics of cases with body stalk anomaly (BSA) and describe the obstetric outcome.MethodRetrospective review of a case series of BSA diagnosed from 2000 to 2010.ResultsAmong the 21 cases, mean gestational age at diagnosis was 22 weeks (range 11–35 weeks). Ten cases elected termination of pregnancy, which was performed at a median gestational age of 24 weeks. One termination of pregnancy at 33 weeks' gestation in a woman with late diagnosis of BSA and a previous uterine scar, required cesarean section during labor because of clinical signs of uterine rupture. Of the remaining 11 cases, four were lost to follow‐up, three delivered vaginally, three underwent elective cesarean sections, and one underwent cesarean section because of obstructed labor. Six of seven cases were growth restricted and six of seven were small for gestational age. There were no abnormal karyotypes among the nine cases which underwent cytogenetic studies.ConclusionContinuation of pregnancy in the presence of BSA is associated with greater maternal risks, in the form of labor complications requiring cesarean section. This information should be discussed with couples at the time of diagnosis. © 2012 John Wiley & Sons, Ltd.
Outcome in fetuses with isolated congenital diaphragmatic hernia with increased nuchal translucency thickness in first trimester
Authors: Spaggiari E. , Stirnemann J. , Ville Y. 
Published: March 2012

ABSTRACTObjectiveTo examine the possible association between increased nuchal translucency (NT) thickness in the first trimester and perinatal outcome in isolated congenital diaphragmatic hernia (CDH).MethodsWe conducted a retrospective study between January 2004 and June 2010. The database was searched to identify all consecutive cases of CDH referred to the fetal medicine center of Necker Hospital in Paris. Enlarged NT was defined above the 95th centile. Only children born alive with an isolated CDH were selected for the analysis of prognostic factors. We also studied the correlation between NT thickness in the first trimester and lung‐to‐head ratio, observed to expected lung area‐to‐head ratio, lung volume estimated by magnetic resonance imaging, and other prenatal features of intrathoracic compression.ResultsSeventy‐one cases of isolated CDH were available. The fetal NT was above the 95th centile in 9 of the 71 cases. Neonatal death occurred in 7/9 (78%) cases with enlarged NT, compared with 24/62 (38%) with normal NT (P = 0.035). Enlarged NT was significantly associated with prenatal features of intrathoracic compression.ConclusionEnlarged NT thickness in CDH is associated with a poor outcome and is related to an early intrathoracic compression. © 2012 John Wiley & Sons, Ltd.
Identification of novel candidate maternal serum protein markers for Down syndrome by integrated proteomic and bioinformatic analysis
Authors: Kang Yuan , Dong Xinran , Zhou Qiongjie , Zhang Ying , Cheng Yan , Hu Rong , Su Cuihong , Jin Hong , Liu Xiaohui , Ma Duan , Tian Weidong , Li Xiaotian 
Published: March 2012

ABSTRACTObjectiveThis study aimed to identify candidate protein biomarkers from maternal serum for Down syndrome (DS) by integrated proteomic and bioinformatics analysis.MethodsA pregnancy DS group of 18 women and a control group with the same number were prepared, and the maternal serum proteins were analyzed by isobaric tags for relative and absolute quantitation and mass spectrometry, to identify DS differentially expressed maternal serum proteins (DS‐DEMSPs). Comprehensive bioinformatics analysis was then employed to analyze DS‐DEMSPs both in this paper and seven related publications.ResultsDown syndrome differentially expressed maternal serum proteins from different studies are significantly enriched with common Gene Ontology functions, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, transcription factor binding sites, and Pfam protein domains, However, the DS‐DEMSPs are less functionally related to known DS‐related genes. These evidences suggest that common molecular mechanisms induced by secondary effects may be present upon DS carrying. A simple scoring scheme revealed Alpha‐2‐macroglobulin, Apolipoprotein A1, Apolipoprotein E, Complement C1s subcomponent, Complement component 5, Complement component 8, alpha polypeptide, Complement component 8, beta polypeptide and Fibronectin as potential DS biomarkers.ConclusionThe integration of proteomics and bioinformatics studies provides a novel approach to develop new prenatal screening methods for noninvasive yet accurate diagnosis of DS. © 2012 John Wiley & Sons, Ltd.
Psychosocial aspects of post‐treatment follow‐up for stage I/II melanoma: a systematic review of the literature
Authors: Rychetnik Lucie , McCaffery Kirsten , Morton Rachael , Irwig Les 
Published: March 2012

AbstractBackgroundPatients treated for melanoma are advised to have lifelong full body skin examinations. Extended intervals between examinations have been proposed, but although this may be clinically effective, psychosocial aspects of follow‐up are not well understood. This systematic review summarised patient and clinician preferences, experiences and adherence with recommended follow‐up of stage I/II melanoma.MethodsMedline, PsycINFO, CINAHL, Embase, Cochrane Library, ACP Journal Club and NHS Economic Evaluation Database were searched from database inception to week 3 April 2010, to identify original studies of psychosocial outcomes of follow‐up after treatment of stage I/II primary cutaneous melanoma, as reported by patients or clinicians. The results were synthesised, and characteristics likely to maximise patients' well‐being and adherence to follow‐up schedules were proposed.ResultsWe found 15 studies that met the inclusion criteria. Anxiety with melanoma follow‐up was common; patients valued reassurance, information and psychosocial support, but long‐term adherence to schedules was variable. Some wanted more emotional support from their clinician than was provided. Clinicians sometimes ordered additional blood and imaging tests to reassure patients. GPs were hesitant to conduct melanoma follow‐up, but a trial providing technical training and protocols reported positive outcomes. Both patients and GPs wanted prompt access to melanoma specialists when suspicious lesions were found.ConclusionPsychosocial aspects of follow‐up impact on patient well‐being and potential adherence to schedules, and may influence clinician practice. If follow‐up schedules or personnel are to be revised, psychosocial impacts on patients must be explicitly addressed, as well as guidance and specialist support for clinicians. Copyright © 2012 John Wiley & Sons, Ltd.