bluuebunny/crossref_metadata_2025_split huggingface dataset:
The expression patterns and correlations of claudin-6, methy-CpG binding protein 2, DNA methyltransferase 1, histone deacetylase 1, acetyl-histone H3 and acetyl-histone H4 and their clinicopathological significance in breast invasive ductal carcinomas
Authors: Xu Xiaoming , Jin Huiying , Liu Yafang , Liu Li , Wu Qiong , Guo Yaxiong , Yu Lina , Liu Zhijing , Zhang Ting , Zhang Xiaowei , Dong Xueyan , Quan Chengshi 
Published: March 2012

AbstractBackgroundClaudin-6 is a candidate tumor suppressor gene in breast cancer, and has been shown to be regulated by DNA methylation and histone modification in breast cancer lines. However, the expression of claudin-6 in breast invasive ductal carcinomas and correlation with clinical behavior or expression of other markers is unclear. We considered that the expression pattern of claudin-6 might be related to the expression of DNA methylation associated proteins (methyl-CpG binding protein 2 (MeCP2) and DNA methyltransferase 1 (DNMT1)) and histone modification associated proteins (histone deacetylase 1 (HDAC1), acetyl-histone H3 (H3Ac) and acetyl- histone H4 (H4Ac)).MethodsWe have investigated the expression of claudin-6, MeCP2, HDAC1, H3Ac and H4Ac in 100 breast invasive ductal carcinoma tissues and 22 mammary gland fibroadenoma tissues using immunohistochemistry.ResultsClaudin-6 protein expression was reduced in breast invasive ductal carcinomas (P< 0.001). In contrast, expression of MeCP2 (P< 0.001), DNMT1 (P= 0.001), HDAC1 (P< 0.001) and H3Ac (P= 0.004) expressions was increased. Claudin-6 expression was inversely correlated with lymph node metastasis (P= 0.021). Increased expression of HDAC1 was correlated with histological grade (P< 0.001), age (P= 0.004), clinical stage (P= 0.007) and lymph node metastasis (P= 0.001). H3Ac expression was associated with tumor size (P= 0.044) and clinical stage of cancers (P= 0.034). MeCP2, DNMT1 and H4Ac expression levels did not correlate with any of the tested clinicopathological parameters (P> 0.05). We identified a positive correlation between MeCP2 protein expression and H3Ac and H4Ac protein expression.ConclusionsOur results show that claudin-6 protein is significantly down-regulated in breast invasive ductal carcinomas and is an important correlate with lymphatic metastasis, but claudin-6 down-regulation was not correlated with upregulation of the methylation associated proteins (MeCP2, DNMT1) or histone modification associated proteins (HDAC1, H3Ac, H4Ac). Interestingly, the expression of MeCP2 was positively correlated with the expression of H3Ac and H3Ac protein expression was positively correlated with the expression of H4Ac in breast invasive ductal carcinomaVirtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/4549669866581452
Cholinergic Abnormalities, Endosomal Alterations and Up-Regulation of Nerve Growth Factor Signaling in Niemann-Pick Type C Disease
Authors: Cabeza Carolina , Figueroa Alicia , Lazo Oscar M , Galleguillos Carolina , Pissani Claudia , Klein Andrés , Gonzalez-Billault Christian , Inestrosa Nibaldo C , Alvarez Alejandra R , Zanlungo Silvana , Bronfman Francisca C 
Published: March 2012

Abstract

Background
Neurotrophins and their receptors regulate several aspects of the developing and mature nervous system, including neuronal morphology and survival. Neurotrophin receptors are active in signaling endosomes, which are organelles that propagate neurotrophin signaling along neuronal processes. Defects in the Npc1 gene are associated with the accumulation of cholesterol and lipids in late endosomes and lysosomes, leading to neurodegeneration and Niemann-Pick type C (NPC) disease. The aim of this work was to assess whether the endosomal and lysosomal alterations observed in NPC disease disrupt neurotrophin signaling. As models, we used i) NPC1-deficient mice to evaluate the central cholinergic septo-hippocampal pathway and its response to nerve growth factor (NGF) after axotomy and ii) PC12 cells treated with U18666A, a pharmacological cellular model of NPC, stimulated with NGF.

Results
NPC1-deficient cholinergic cells respond to NGF after axotomy and exhibit increased levels of choline acetyl transferase (ChAT), whose gene is under the control of NGF signaling, compared to wild type cholinergic neurons. This finding was correlated with increased ChAT and phosphorylated Akt in basal forebrain homogenates. In addition, we found that cholinergic neurons from NPC1-deficient mice had disrupted neuronal morphology, suggesting early signs of neurodegeneration. Consistently, PC12 cells treated with U18666A presented a clear NPC cellular phenotype with a prominent endocytic dysfunction that includes an increased size of TrkA-containing endosomes and reduced recycling of the receptor. This result correlates with increased sensitivity to NGF, and, in particular, with up-regulation of the Akt and PLC-γ signaling pathways, increased neurite extension, increased phosphorylation of tau protein and cell death when PC12 cells are differentiated and treated with U18666A.

Conclusions
Our results suggest that the NPC cellular phenotype causes neuronal dysfunction through the abnormal up-regulation of survival pathways, which causes the perturbation of signaling cascades and anomalous phosphorylation of the cytoskeleton.
Microbial community analysis in biocathode microbial fuel cells packed with different materials
Authors: Sun Yanmei , Wei Jincheng , Liang Peng , Huang Xia 
Published: March 2012

Abstract
Biocathode MFCs using microorganisms as catalysts have important advantages in lowering cost and improving sustainability. Electrode materials and microbial synergy determines biocathode MFCs performance. In this study, four materials, granular activated carbon (GAC), granular semicoke (GS), granular graphite (GG) and carbon felt cube (CFC) were used as packed cathodic materials. The microbial composition on each material and its correlation with the electricity generation performance of MFCs were investigated. Results showed that different biocathode materials had an important effect on the type of microbial species in biocathode MFCs. The microbes belonging to Bacteroidetes and Proteobacteria were the dominant phyla in the four materials packed biocathode MFCs. Comamonas of Betaproteobacteria might play significant roles in electron transfer process of GAC, GS and CFC packed biocathode MFCs, while in GG packed MFC Acidovorax may be correlated with power generation. The biocathode materials also had influence on the microbial diversity and evenness, but the differences in them were not positively related to the power production.
Neuronal nitric oxide synthase regulates endothelial inflammation
Authors: Chakrabarti Subhadeep , Chan Carmen K , Jiang Yanyan , Davidge Sandra T 
Published: March 2012

ABSTRACTNO, produced by the endothelium, is a modulator of vascular inflammation. Traditionally, eNOS was believed to be the primary source of NO in the endothelium. However, recent data suggest an important role for nNOS in the endothelium, although little is known about factors regulating this novel eNOS. We examined the localization, regulation, and significance of endothelial nNOS in this study. Primary HUVECs were used as a model system. Inflammatory changes were induced by stimulation with TNF. We report that unlike eNOS, nNOS is predominantly localized to the nucleus of resting endothelial cells. This nNOS also contributed to basal NO production in the resting endothelium. Ablation of endothelial nNOS by pharmacological inhibition (using L-NPA) or siRNA further enhanced cytokine-mediated inflammatory responses, such as up-regulation of VCAM-1 and proinflammatory cytokines, as well as increased leukocyte recruitment. Based on these findings, we suggest a potential anti-inflammatory role of endothelial nNOS that can attenuate unopposed, proinflammatory cytokine actions. Our data indicate a novel location and an immunoregulatory role for nNOS in the endothelium.
The transformation suppressor gene Reck is required for postaxial patterning in mouse forelimbs
Authors: Yamamoto Mako , Matsuzaki Tomoko , Takahashi Rei , Adachi Eijiro , Maeda Yasuhiro , Yamaguchi Sachiyo , Kitayama Hitoshi , Echizenya Michiko , Morioka Yoko , Alexander David B. , Yagi Takeshi , Itohara Shigeyoshi , Nakamura Takashi , Akiyama Haruhiko , Noda Makoto 
Published: March 2012

Summary
The membrane-anchored metalloproteinase-regulator RECK has been characterized as a tumor suppressor. Here we report that mice with reduced Reck-expression show limb abnormalities including right-dominant, forelimb-specific defects in postaxial skeletal elements. The forelimb buds of low-Reck mutants have an altered dorsal ectoderm with reduced Wnt7a and Igf2 expression, and hypotrophy in two signaling centers (i.e., ZPA and AER) that are essential for limb outgrowth and patterning. Reck is abundantly expressed in the anterior mesenchyme in normal limb buds; mesenchyme-specific Reck inactivation recapitulates the low-Reck phenotype; and some teratogens downregulate Reck in mesenchymal cells. Our findings illustrate a role for Reck in the mesenchymal-epithelial interactions essential for mammalian development.
Bone metastases from prostate, breast and multiple myeloma: differences in lesion conspicuity at short-tau inversion recovery and diffusion-weighted MRI
Authors: Pearce T , Philip S , Brown J , Koh D M , Burn P R 
Published: March 2012

Objectives: The objective of this study was to compare the relative conspicuity of bone metastases on short-tau inversion recovery (STIR) and diffusion-weighted MRI (DWI) whole-body MR sequences for breast, prostate and myeloma malignancies.
Methods: 44 whole-body MRI scans were reviewed retrospectively (coronal T 1 weighted, STIR and DWI with b=800). On each scan, up to four of the largest bone lesions were identified on T 1 weighting, and the region of interest signal intensity was measured on STIR and DWI, as well as the background signal intensity. The mean lesion signal to background ratio was calculated for each patient and then for each malignancy group.
Results: In prostate cancer patients, the DWI signal/background ratio was greater than that of STIR in 22 out of 24 patients (mean DWI lesion/background ratio 3.91, mean STIR lesion/background ratio 2.31; p=0.0001). In multiple myeloma, the DWI ratio was higher in 6/7 patients (DWI group mean ratio 7.59, STIR group mean ratio 3.7; p=0.0366). In 13 breast cancer patients, mean STIR and DWI signal/background were similar (DWI group mean ratio 4.13, group mean STIR ratio 4.26; p=0.8587).
Conclusion: Bone lesion conspicuity measured by lesion/background signal intensity was higher on DWI b=800 than on STIR in patients with prostate cancer and multiple myeloma. DWI should be used in whole-body MR oncology protocols in these conditions to maximise lesion detection.
Tumour recurrence and enlargement in patients with craniopharyngioma with and without GH replacement therapy during more than 10 years of follow-up
Authors: Olsson D S , Buchfelder M , Wiendieck K , Kremenevskaja N , Bengtsson B-Å , Jakobsson K-E , Jarfelt M , Johannsson G , Nilsson A G 
Published: March 2012

ObjectiveMost patients who have been treated for craniopharyngioma (CP) are GH deficient (GHD). GH replacement therapy (GHRT) may stimulate tumour regrowth; and one of the concerns with long-term GHRT is the risk of tumour progression. Therefore, the objective was to study tumour progression in CP patients on long-term GHRT.DesignCase–control study.Patients and methodsThe criteria for inclusion of cases were: i) GHD caused by CP; ii) GHRT >3 years; and iii) regular imaging. This resulted in 56 patients (mean age at diagnosis 25±16 years) with a mean duration of GHRT of 13.6±5.0 years. As controls, 70 CP patients who had not received GHRT were sampled with regard to follow-up, gender, age at diagnosis and initial radiation therapy (RT).ResultsThe 10-year tumour progression-free survival rate (PFSR) for the entire population was 72%. There was an association (hazard ratio, P value) between PFSR and initial RT (0.13, <0.001) and residual tumour (3.2, <0.001). The 10-year PFSR was 88% for the GHRT group and 57% for the control group. Substitution with GHRT resulted in the following associations to PFSR: GHRT (0.57, 0.17), initial RT (0.16, <0.001), residual tumour (2.6, <0.01) and gender (0.57, 0.10). Adjusted for these factors, the 10-year PFSR was 85% for the GHRT group and 65% for the control group.ConclusionsIn patients with CP, the most important prognostic factors for the PFSR were initial RT and residual tumour after initial treatment. Long-term GHRT did not affect the PFSR in patients with CP.
NOMA: A Preventable “Scourge” of African Children
Authors: Ogbureke Kalu U.E , Ogbureke Ezinne I 
Published: March 2012

Noma is a serious orofacial gangrene originating intraorally in the gingival-oral mucosa complex before spreading extraorally to produce a visibly destructive ulcer. Although cases of noma are now rarely reported in the developed countries, it is still prevalent among children in third world countries, notably in sub-Sahara Africa, where poverty, ignorance, malnutrition, and preventable childhood infections are still common. This review summarizes historical, epidemiological, management, and research updates on noma with suggestions for its prevention and ultimate global eradication. The global annual incidence remains high at about 140,000 cases, with a mortality rate exceeding 90% for untreated diseases. Where the patients survive, noma defects result in unsightly facial disfigurement, intense scarring, trismus, oral incompetence, and social alienation. Although the etiology has long been held to be infectious, a definitive causal role between microorganisms cited, and noma has been difficult to establish. The management of noma with active disease requires antibiotics followed by reconstructive surgery. Current research efforts are focused towards a comprehensive understanding of the epidemiology, and further elucidation of the microbiology and pathogenesis of noma.Although a formidable public health challenge, noma can be prevented with a potential for subsequent global eradication. To achieve both desirable goals, detection of early disease is crucial because these early lesions respond to conventional antibiotic treatments when instituted side by side with nutritional rehabilitation, and obviates the necessity for extensive surgical reconstruction often indicated in late stage disease. The eradication of noma in the developed world in the mid 20thcentury bears out the notion of a similar outcome following effective preventive strategies in Africa. A fundamental and necessary step towards attaining this goal is for the international community to adopt a perception of noma as an urgent global public health challenge. Research effort toward deciphering the microbiology, molecular events, and pathogenesis of noma also should intensify.
Estimating Hepatic Glucokinase Activity Using a Simple Model of Lactate Kinetics
Authors: Stefanovski Darko , Youn Jang H. , Rees Matthew , Watanabe Richard M. , Ader Marilyn , Ionut Viorica , Jackson Anne U. , Boehnke Michael , Collins Francis S. , Bergman Richard N. 
Published: March 2012

OBJECTIVE
Glucokinase (GCK) acts as a component of the “glucose sensor” in pancreatic β-cells and possibly in other tissues, including the brain. However, &gt;99% of GCK in the body is located in the liver, where it serves as a “gatekeeper”, determining the rate of hepatic glucose phosphorylation. Mutations in GCK are a cause of maturity-onset diabetes of the young (MODY), and GCKR, the regulator of GCK in the liver, is a diabetes susceptibility locus. In addition, several GCK activators are being studied as potential regulators of blood glucose. The ability to estimate liver GCK activity in vivo for genetic and pharmacologic studies may provide important physiologic insights into the regulation of hepatic glucose metabolism.

RESEARCH DESIGN AND METHODS
Here we introduce a simple, linear, two-compartment kinetic model that exploits lactate and glucose kinetics observed during the frequently sampled intravenous glucose tolerance test (FSIGT) to estimate liver GCK activity (KGK), glycolysis (K12), and whole body fractional lactate clearance (K01).

RESULTS
To test our working model of lactate, we used cross-sectional FSIGT data on 142 nondiabetic individuals chosen at random from the Finland–United States Investigation of NIDDM Genetics study cohort. Parameters KGK, K12, and K01 were precisely estimated. Median model parameter estimates were consistent with previously published values.

CONCLUSIONS
This novel model of lactate kinetics extends the utility of the FSIGT protocol beyond whole-body glucose homeostasis by providing estimates for indices pertaining to hepatic glucose metabolism, including hepatic GCK activity and glycolysis rate.
Longitudinal Trajectories of HbA1c and Fasting Plasma Glucose Levels During the Development of Type 2 Diabetes
Authors: Heianza Yoriko , Arase Yasuji , Fujihara Kazuya , Hsieh Shiun Dong , Saito Kazumi , Tsuji Hiroshi , Kodama Satoru , Yahagi Naoya , Shimano Hitoshi , Yamada Nobuhiro , Hara Shigeko , Sone Hirohito 
Published: March 2012

OBJECTIVE
To describe the trajectory of HbA1c and glucose concentrations before the diagnosis of diabetes.

RESEARCH DESIGN AND METHODS
The study comprised 1,722 nondiabetic Japanese individuals aged 26–80 years. Fasting plasma glucose (FPG) and HbA1c were measured annually for a mean of 9.5 (SD 1.8) years.

RESULTS
Diabetes occurred in 193 individuals (FPG ≥7.0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA1c ≥6.5%). Mean HbA1c values were &gt;5.6% each year before diagnosis in diabetes cases. Mean HbA1c (5.69% [95% CI 5.50–5.88]) was higher in the 21 individuals who developed diabetes 10 years after the baseline examination than in nondiabetic individuals after 10 years (5.27% [5.25–5.28]). From 3 years to 1 year prediagnosis, HbA1c increased 0.09% (SE 0.01)/year, reaching 5.90% (5.84–5.96) 1 year prediagnosis. In the entire group, marked increases in HbA1c of 0.3% (SE 0.05%)/year and FPG of 0.63 (0.07) mmol/L/year predicted diabetes.

CONCLUSIONS
HbA1c trajectory increased sharply after gradual long-term increases in diabetic individuals.
Pathogenetic mechanisms of posttraumatic fibrosis of the uterus of white rats
Authors: Novikov Nikolay , Dolomatov Sergey , Zukow Walery , Volyanskaya Alla , Napierala Marek , Hagner-Derengowska Magdalena , Kazmierczak Urszula , Skaliy Aleksander 
Published: March 2012

Abstract
Stereo bearings-only tracking of a wheelchair from a robot
Authors: Di Benedetto S. , Marhic B. , Delahoche L. 
Published: March 2012

Abstract
This project deals with technical assistance for people of reduced mobility. The goal of this work is to have a mobile platform with an embedded prehensive arm (MANUS®) track a wheelchair. The use of this mobile unit in relation to the patient’s wheelchair is carried out on a master-slave basis. This study, therefore, has a plural-disciplinary nature: Science for the Engineer, Human, Social and Clinical Sciences. To ensure the tracking of the wheelchair by the mobile platform, we applied a stereo bearings-only tracking (BOT) paradigm to a single moving target. The observer, the mobile platform (robot), is equipped with two omnidirectional vision sensors, that each provides output with which we compute two bearing angles. Having two bearing angles makes it possible to track a manoeuvring target. In this paper we will show how we take advantage of the multi-sensor data fusion to improve the BOT process and hence obtain a more reliable wheelchair tracking.
A study on hemopoisis and differentiation of dendritic cells from primitive CD34 haematopoietic stem cells from CML patients
Authors: Gaafar Ameera 
Published: March 2012

AbstractHaematopoietic stem cell transplantation (HSCT) is the treatment of choice for patients with refractory leukemia. However, HSCT is associated with lethal GVHD and/or disease relapse. The addition of alternative remedies such as adoptive immunotherapy may lead to eradication of minimal residual leukemia and prevention of relapse. Antigen-pulsed ex-vivo dendritic cells (DCs) have been utilized for the initiation of such immunotherapeutic modalities. DCs can successfully be generated from CD34+ haematopoietic stem cells (HPSCs) and DCs generated from patients with chronic myeloid leukemia (CML), displayed clonal heterogeneity with respect to the expression of the bcr/abl fusion gene. One reason could be that, DCs mixtures were originated from diverse sources of normal and leukemia either CD34+ or CD34- HPSC. CD34-HPSCs were reported to possess hematopoisis reconstitution capabilities. So far, the differentiation of DCs from CD34- HPSCs and their expression of bcr/abl have not been explored in CML patients. Consequently, we hypothesized that CD34-HPSCs could be a valuable source for the generation of an effective vaccine which could be stored and used latter to target residual leukemia if the patient encountered any relapses.Our study showed that DCs generated from CD34-HPSCs were potent and efficient antigen presenting cells and comparable to their counterparts DCs from CD34+ HPSCs and hold promises in immunotherapy modality.1A. Gaafar, 2H. M. Al-Omar, 1Z. Al-Mokhlafi, 1Manogaran PS, 1A. qniebi1, 1A Al-Mazrou, 2F.Al Mohareb, 1C. Adra, 1K. Al-hussein1Stem Cells Therapy Program, 2 King Faisal Cancer Center, King Faisal Specialist Hospital & Research Centre.11211Riyadh, Saudi Arabia
Ethical Issues in Egg and Embryo Donation: Informed Consent
Authors: Iltis Ana 
Published: March 2012

AbstractThe use of human eggs and embryos in embryonic stem cell research raises numerous ethical issues and questions. This presentation addresses a range of ethical issues regarding the informed consent of persons who donate embryos for use in stem cell research or who donate gametes (egg or sperm) that lead to the creation of embryos that are donated for use in research. Informed consent refers to the process in which clinicians or researchers obtain permission from patients or potential research subjects prior to doing a procedure or enrolling the person in a study. The presentation will explain the main reasons for obtaining informed consent from persons during different stages of the process of donating gametes and creating or donating embryos for research. Special attention will be given to the local and international guidelines regarding informed consent, to the conditions necessary for obtaining informed consent, and to possible barriers to informed consent.