bluuebunny/crossref_metadata_2025 huggingface dataset:
Amperometric carbon paste enzyme electrodes for uric acid determination with different mediators
Authors: Erden Pinar Esra , Pekyardimci Şule , Kiliç Esma
Published: August 2011

In this study, two new amperometric carbon paste enzyme electrodes for determination of uric acid were developed. The carbon paste was prepared by mixing uricase enzyme, 1,4-benzoquinone or poly(vinylferrocene) (PVF) as a mediator, graphite powder, paraffin oil and then the paste was placed into cavity of a teflon electrode body. Determination of uric acid was performed by oxidation of enzymatically generated H2O2. The effects of enzyme loading, mediator amount, buffer type, pH, buffer concentration, working potential and temperature were investigated for both electrodes. The working range of the 1,4-benzoquinone modified enzyme electrode was 1.9 × 10–8–2.7 × 10–3 M, detection limit 1.9 × 10–8 M and response time 150 s. Optimum buffer type, pH, buffer concentration, working potential, temperature and amounts of enzyme and mediator for 1,4-benzoquinone modified enzyme electrode were found to be Tris, 8.0, 0.20 M, +0.25 V, 30 °C, 2.0 Unit and 13%, respectively. The working range of the PVF modified enzyme electrode was 7.4 × 10–8–7.0 × 10–3 M, detection limit 7.4 × 10–8 M and response time 120 s. Optimum buffer type, pH, buffer concentration, working potential, temperature and amounts of enzyme and mediator for PVF modified enzyme electrode were found to be phosphate, 8.0, 0.05 M, +0.70 and +0.30 V, 40 °C, 2.0 Unit and 10.9%, respectively. The repeatability, storage stability of the enzyme electrodes and interference effects were also investigated. Enzyme electrodes were used for determination of uric acid in serum samples and the results were in a good agreement with those obtained by commercial enzymatic kits.
Molecular Markers in Cutaneous Squamous Cell Carcinoma
Authors: Tufaro Anthony P. , Chuang Jim C.-M. , Prasad Nijaguna , Chuang Alice , Chuang Tony C. , Fischer Anne C.
Published: August 2011

Nonmelanoma skin carcinoma (NMSC) is the most frequent cancer in the USA with over 1.3 million new diagnoses a year; however due to an underappreciation of its associated mortality and growing incidence and its ability to be highly aggressive, the molecular mechanism is not well delineated. Whereas the molecular profiles of melanoma have been well characterized, those for cutaneous squamous cell carcinoma (cSCC) have trailed behind. This importance of the new staging paradigm is linked to the ability currently to better clinically cluster similar biologic behavior in order to risk-stratify lesions and patients. In this paper we discuss the trends in NMSC and the etiologies for the subset of NMSC with the most mortality, cutaneous SCC, as well as where the field stands in the discovery of a molecular profile. The molecular markers are highlighted to demonstrate the recent advances in cSCC.
The Prevalence, Abundance, and Density ofPseudoterranovasp. (p) Larvae in the Flesh of Cod (Gadus morhua) Relative to Proximity of Grey Seal (Halichoerus grypus) Colonies on the Coast off Drangar, Northwest Iceland
Authors: Hauksson Erlingur
Published: August 2011

About 300 cod (Gadus morhua) were sampled on three different sites of different proximity to grey seals (Halichoerus grypus), which are the most important final host forPseudoterranova krabbei, off Drangar, Northwest Iceland, in the summer of 2004. Cod caught at each station were grouped into four sizes: (1) 40–54 cm, (2) 55–59 cm, (3) 60–69 cm and, (4) >70 cm. Difference in prevalence between catch-sites were analyzed by a binary logistic regression model. Abundance, and density were investigated with multiple regressions. As expected prevalence, abundance and density ofPseudoterranovalarvae were highest in the fish caught closest to shore, which was also in closest proximity to grey seal colonies and in the shallowest waters. In the closest proximity to grey seal colonies and in the shallowest water, the prevalence and abundance of sealworm larvae increased with increased length of fish. Finally, the density ofPseudoterranovalarvae in cod declined exponentially with depth: 50% at 65 meters and almost zero at 210 meters. In the paper these observations were discussed in relation to sealworm eggs dispersal, depth gradient off the coast, temperature tolerance of the sealworm ovum, and behavioral types of Icelandic cod.
Protein and Amino Acid Supplementation Does Not Alter Proteolytic Gene Expression following Immobilization
Authors: Bunn Jennifer A. , Buford Thomas W. , Serra Monica C. , Kreider Richard B. , Willoughby Darryn S.
Published: August 2011

Objective. To determine if supplementation of protein and amino acids (PAA) decreases skeletal muscle expression of atrophy-related genes, muscle mass, and strength during immobilization in humans.Methods. Twenty males wore a lower-limb immobilization boot for 28 days and consumed either a PAA supplement (28 g protein) or carbohydrate placebo (28 g maltodextrose), while consuming their normal daily diet. Testing sessions included dietary analysis, lower-leg girth and body composition measurements, strength testing, and gastrocnemius muscle biopsies. Muscle was analyzed for mRNA expression of markers in the ubiquitin and calpain systems, myostatin, TNF-α, and NF-κB.Results. All genes of interest increased over time (P<.05), but there was no difference between groups. Lower-leg girth decreased over time (P=0.02); however, there were no significant changes in body composition or strength.Conclusion. Short-term lower-limb disuse, despite the absence of significant muscle atrophy, is associated with increases in skeletal muscle gene expression of several proteolysis-related genes. These changes do not appear to be altered by oral PAA supplementation.
Optimization of a Pumped‐Storage Fixed‐Head Hydroplant: The Bang‐Singular‐Bang Solution
Authors: Bayón L. , Grau J. M. , Ruiz M. M. , Suárez P. M.
Published: August 2011

We consider the problem of the optimization of the functioning of a pumped‐storage hydroplant. The problem can be mathematically formulated as an optimal control problem, and when the considered hydromodel is of the fixed‐head type, an added complication arises: the solution is of the bangsingular‐bang type. In this paper, we propose a simple and efficient optimization algorithm to find the solution.
Heterogeneous Computing for Vertebra Detection and Segmentation in X-Ray Images
Authors: Lecron Fabian , Mahmoudi Sidi Ahmed , Benjelloun Mohammed , Mahmoudi Saïd , Manneback Pierre
Published: August 2011

The context of this work is related to the vertebra segmentation. The method we propose is based on the active shape model (ASM). An original approach taking advantage of the edge polygonal approximation was developed to locate the vertebra positions in a X-ray image. Despite the fact that segmentation results show good efficiency, the time is a key variable that has always to be optimized in a medical context. Therefore, we present how vertebra extraction can efficiently be performed in exploiting the full computing power of parallel (GPU) and heterogeneous (multi-CPU/multi-GPU) architectures. We propose a parallel hybrid implementation of the most intensive steps enabling to boost performance. Experimentations have been conducted using a set of high-resolution X-ray medical images, showing a global speedup ranging from 3 to 22, by comparison with the CPU implementation. Data transfer times between CPU and GPU memories were included in the execution times of our proposed implementation.
Similarity Solutions of Partial Differential Equations in Probability
Authors: Lefebvre Mario
Published: August 2011

Two‐dimensional diffusion processes are considered between concentric circles and in angular sectors. The aim of the paper is to compute the probability that the process will hit a given part of the boundary of the stopping region first. The appropriate partial differential equations are solved explicitly by using the method of similarity solutions and the method of separation of variables. Some solutions are expressed as generalized Fourier series.
Grazing Effects of Fish versus Sea Urchins on Turf Algae and Coral Recruits: Possible Implications for Coral Reef Resilience and Restoration
Authors: Korzen Leor , Israel Alvaro , Abelson Avigdor
Published: August 2011

Herbivory is an important structuring factor in coral reefs, influencing seaweed abundance, competitive interactions between seaweeds and corals, and coral reef resilience. Despite reports of a drastic increase in the cover of benthic algae and turf dominancy in the coral reefs of Eilat, Red Sea, very little is known about the factors responsible for this phenomenon or the possible effects of herbivory on turf algae and coral recruits. Here, we examine the effects of herbivory by experimentally exposing turf algae and coral recruits to grazing activities of herbivorous fish and sea urchins. Using remote video cameras to document removal of algae and coral spats, we show that the main grazing impact is due to daily grazing by fishes, whereas the significant impact of sea urchins is mainly expressed in their adverse effect on the survival of coral recruits, with a relatively low effect on algal biomass. These findings contribute to our understanding of the factors influencing turf algae establishment and proliferation, and the survival of coral recruits on the coral reefs of Eilat. The clear differences between the impact of herbivorous fish and that of sea urchins, on the Eilat reefs, have critical implications for reef resilience and restoration measures.
CATHARE Assessment of Natural Circulation in the PKL Test Facility during Asymmetric Cooldown Transients
Authors: Bousbia Salah Anis , Vlassenbroeck Jacques
Published: August 2011

Results of the CATHARE code calculations related to asymmetric cooldown tests in the PKL facility are presented. The test under consideration is the G2.1 experiment performed within the OECD/NEA PKL-2 project. It consists of carrying out a cooldown under natural circulation conditions in presence of two (out of four) emptied Steam Generators (SGs) and isolated on their secondary sides. The main goal of the current study is to assess the impact of a chosen cooldown strategy upon the occurrence of a Natural Circulation Interruption (NCI) in the inactive (i.e., noncooling) loops. For this purpose, three G2.1 test runs were investigated. The calculation results emphasize, mainly, the effect of the cooldown strategy, and the conditions that could lead to the occurrence of the NCI phenomenon.
Targeting the Microtubular Network as a New Antimyeloma Strategy
Authors: Feng Rentian , Li Shirong , Lu Caisheng , Andreas Carrie , Stolz Donna B. , Mapara Markus Y. , Lentzsch Suzanne
Published: August 2011

We identified nocodazole as a potent antimyeloma drug from a drug screening library provided by the Multiple Myeloma Research Foundation. Nocodazole is a benzimidazole that was originally categorized as a broad-spectrum anthelmintic drug with antineoplastic properties. We found that nocodazole inhibited growth and induced apoptosis of primary and multiresistant multiple myeloma cells cultured alone and in the presence of bone marrow stromal cells. Nocodazole caused cell-cycle prophase and prometaphase arrest accompanied by microtubular network disarray. Signaling studies indicated that increased expression of Bim protein and reduced X-linked inhibitor of apoptosis protein and Mcl-1L levels were involved in nocodazole-induced apoptosis. Further investigation showed Bcl-2 phosphorylation as a critical mediator of cell death, triggered by the activation of c-jun-NH2 kinase (JNK) instead of p38 kinase or extracellular signal–regulated kinases. Treatment with JNK inhibitor decreased Bcl-2 phosphorylation and subsequently reduced nocodazole-induced cell death. Nocodazole combined with dexamethasone significantly inhibited myeloma tumor growth and prolonged survival in a human xenograft mouse model. Our studies show that nocodazole has potent antimyeloma activity and that targeting the microtubular network might be a promising new treatment approach for multiple myeloma. Mol Cancer Ther; 10(10); 1886–96. ©2011 AACR.
Macrophage-Dependent Cleavage of the Laminin Receptor α6β1 in Prostate Cancer
Authors: Sroka Isis C. , Sandoval Cynthia P. , Chopra Harsharon , Gard Jaime M. C. , Pawar Sangita C. , Cress Anne E.
Published: August 2011

The laminin-binding integrin α6β1 plays a major role in determining the aggressive phenotype of tumor cells during metastasis. Our previous work has shown that cleavage of the α6β1 integrin to produce the structural variant α6pβ1 on tumor cell surfaces is mediated by the serine protease urokinase plasminogen activator (uPA). Cleavage of α6β1 increases tumor cell motility, invasion, and prostate cancer metastasis, and blockage of uPA inhibits α6pβ1 production. In human tumors, uPA and uPAR are expressed in tumor cells and tumor-associated macrophages (TAM). TAMs localize to solid tumors and contribute to increased tumor growth and the metastatic phenotype. In this study, we utilized a coculture system of PC-3 prostate tumor cells and macrophages [12-O-tetradecanoylphorbol-13-acetate (TPA)-differentiated human leukemia HL-60 cells] to investigate the hypothesis that macrophages stimulate the production of the prometastatic variant α6pβ1 on human prostate cancer cells via the uPA/uPAR axis. Our results indicate that adherent macrophages cocultured with PC-3 cells increased PC-3 uPAR mRNA, uPAR cell surface protein expression and α6 integrin cleavage. The stimulation does not require macrophage/tumor cell contact because macrophage conditioned medium is sufficient for increased uPAR transcription and α6 cleavage–dependent PC-3 cell invasion. The increased cleavage was dependent on uPAR because production was blocked by silencing RNA–targeting uPAR. These results indicate that macrophages can stimulate uPA/uPAR production in tumor cells which results in α6 integrin cleavage. These data suggest that TAMs promote prometastatic integrin-dependent pericellular proteolysis. Mol Cancer Res; 9(10); 1319–28. ©2011 AACR.
Co-Inheritance of β- and δ-Thalassemia Compromising Prenatal Screening in a Chinese Couple Seeking Prevention
Authors: Li Jian , Xie Xing-Mei , Zhou Jian-Ying , Li Dong-Zhi
Published: August 2011

Although δ-globin gene mutations have no clinical implications, association of β- and δ-thalassemia may lead to misdiagnosis. We describe the case of a Chinese woman who was assumed to have an α-thalassemia heterozygote, but was later shown to have β-thalassemia with a normal amount of HbA2 caused by the –77 mutation of the δ-globin gene. This study highlights the importance of considering δ-thalassemia during β-thalassemia screening to avoid false-negative results in the detection of at-risk couples.
Comparison of the Efficacy of Three Progestins in the Treatment of Simple Endometrial Hyperplasia without Atypia
Authors: Ozdegirmenci Ozlem , Kayikcioglu Fulya , Bozkurt Ulku , Akgul Mehmet Akif , Haberal Ali
Published: August 2011

Aim: To evaluate the treatment of endometrial hyperplasia (EH) with different progestins. Methods: Eighty-two women with simple EH without atypia were included. Patients were offered oral progestagens and were randomized to one of three options for 3 months: medroxyprogesterone acetate (MPA, 10 mg/day), lynestrenol (LYN, 15 mg/day) and norethisterone (NET, 15 mg/day) for 10 days per cycle. Patients were reevaluated after treatment. Women diagnosed with proliferative and nonatypical EH at the second curettage were offered the same progestins for another 3 months. The primary outcome of the study was the proportion of women requiring further treatment. Results: Of the 82 women, 46 (56.1%) received MPA (23.2%), LYN (13.4%) and NET (19.5%) therapy for another 3 months at the end of the first 3 months of treatment. The patients receiving MPA showed resolution in 36.7% of the cases versus 37% in the NET group. The highest resolution rate (56%) was observed in the LYN group, although there was no statistically significant difference between progestins regarding the proportion of women requiring further treatment (χ2 = 2.608; p = 0.271). Conclusion: It seems that the efficacies of oral progestins are similar at these dosages in simple EH without atypia.
Dose-Dependent Effect of Sphingosine-1-Phosphate in Mouse Oocyte Maturation Medium on Subsequent Embryo Development
Authors: Jee Byung Chul , Jo Jun Woo , Suh Chang Suk , Kim Seok Hyun
Published: August 2011

Aim: To investigate the dose-dependent effect of sphingosine-1-phosphate (S1P) supplementation on meiotic maturation, apoptosis and developmental competence of immature mouse oocytes. Methods: Immature oocytes from 5- to 6-week-old BDF1 mice were incubated in maturation medium containing S1P with six different doses (10 nM, 50 nM, 100 nM, 500 nM, 1 µM, and 2 µM) for 18–19 h. Fertilization and blastocyst formation was assessed. All blastocysts were stained by anti-caspase antibody. Results: Treatment with 100 nM, 500 nM and 1 µM S1P showed significantly higher blastulation rate [66.0, 62.1 and 66.2%, respectively, p < 0.05 when compared with control (40.0%)]. Blastomere count was similar across six treatment groups, but the percentage of apoptotic blastomere was significantly lower in the 100 nM, 500 nM, and 2 µM S1P-treated groups [5.4, 6.5, and 3.7%, respectively, p < 0.05 when compared with control (10.6%)]. Conclusion: Considering the blastulation rate together with the apoptotic event in the blastocysts, adding 100 and 500 nM S1P within oocyte maturation medium could be beneficial in the development of immature mouse oocytes.
Effects of 4-Hydroxy-2-Nonenal, a Major Lipid Peroxidation-Derived Aldehyde, and N-Acetylcysteine on the Cyclooxygenase-2 Expression in Human Uterine Myometrium
Authors: Temma-Asano Kumiko , Tskitishvili Ekaterine , Kanagawa Takeshi , Tomimatsu Takuji , Tsutsui Tateki , Kimura Tadashi , Chang Yang Sil , Nakamura Takafumi , Nakai Yuichiro , Shimoya Koichiro
Published: August 2011

Background: Chorioamnionitis is one of the important causes of preterm labor. Preterm labor with chorioamnionitis is associated with oxidative stress. We reported that 4-hydroxy-2-nonenal (4-HNE), a major end product of oxidative fatty acid metabolism, is accumulated in the placenta with chorioamnionitis. The aim of this study was to confirm the effect of 4-HNE on cyclooxygenase-2 (COX-2) and prostaglandin (PG) induction in the uterine myometrial tissues. We also examined the effect of N-acetylcysteine (NAC) on 4-HNE-induced COX-2 expression. Methods: Uterine myometrial tissues were obtained from 5 patients. One of them underwent elective cesarean section without labor, and 4 of them underwent hysterectomy because of placental previa or atonic bleeding. We stimulated the uterine myometrial tissues with 4-HNE. In addition, the tissues were pretreated with NAC before 4-HNE treatment. The expression of COX-2 mRNA was observed by real-time PCR. PGE2 and prostacyclin release into the supernatants of the tissue cultures was measured by ELISA. Results: 4-HNE induced the COX-2 mRNA expression and PGE2 production in the uterine myometrial tissue culture in a dose-dependent and time-dependent manner. NAC inhibited 4-HNE-induced COX-2 expression. Conclusion: 4-HNE may play an important role in preterm labor. NAC might be protective against preterm labor under oxidative stress.
Splenic Circumference at Midpregnancy as a Predictor of Hemoglobin Bart’s Disease among Fetuses at Risk
Authors: Srisupundit Kasemsri , Tongprasert Fuanglada , Luewan Suchaya , Sirichotiyakul Supatra , Tongsong Theera
Published: August 2011

Objective: To determine the accuracy of splenic circumference in predicting hemoglobin (Hb) Bart’s disease among fetuses at risk at midpregnancy. Materials and Methods: Women with singleton pregnancies with a fetal risk of Hb Bart’s disease were enrolled in the study at 18–22 weeks of gestation. All underwent splenic circumference measurement before cordocentesis for fetal blood analysis. The final diagnosis used as a gold standard was based on fetal Hb typing using high-performance liquid chromatography. Results: Among all the pregnancies, the prevalence of Hb Bart’s disease was 26.1% (87/334 fetuses). Twenty-four fetuses (27.6%) had some degree of hydropic changes. Notably, of these 24, 22 showed splenomegaly as well. When hydropic fetuses were excluded, the sensitivity, specificity, positive predictive value and negative predictive value of splenic circumference in identifying affected fetuses were 68.3, 83.0, 50.6 and 91.1%, respectively. Conclusion: Splenic circumference measurement at midpregnancy may be helpful in distinguishing affected fetuses from those unaffected. Among couples at risk with normal splenic size, the risk of having an affected child is much lower, whereas the enlarged spleen places the pregnancy at a higher risk. This information may help couples decide on invasive diagnosis or a noninvasive approach.
Prediction of Birth Weight Discordance in Twin Pregnancies by Second- and Third- Trimester Ultrasound
Authors: Hoopmann Markus , Kagan Karl O. , Yazdi Britta , Grischke Eva-Maria , Abele Harald
Published: August 2011

Introduction: Our purpose was to examine whether the prenatal prediction of a critical birth weight discordance (BWD) in twin pregnancies can be improved by using either different formulae for prenatal fetal weight estimation or single biometric measurements or by assessing the intertwin discordance in the second trimester rather than shortly before birth. Material and Methods: We conducted a retrospective study involving 196 twin pregnancies with an ultrasound examination between 18 and 25 weeks of gestation and one within 14 days prior to delivery. The accuracy was assessed by comparing the prenatal intertwin discordance (PID) with the BWD. PID was estimated by 5 common fetal weight estimation formulae and by single biometric measurements prior to delivery and in the second trimester. Results: The fetal weight estimation accuracy was similar in mono- and dichorionic pregnancies and the smaller and the larger twin. PID was most accurate with the fetal weight estimation formulae prior to delivery. The second-trimester measurements resulted in an underestimation of the BWD. Detection and false-positive rates for a BWD ≧20% were about 65 and 15%. Discussion: About two thirds of the twin pregnancies with a relevant BWD can be detected prior to delivery. An optimal detection rate requires fetal weight estimation close to delivery.
Prevalence and Outcome of Absence of Ductus Venosus at 11+0 to 13+6 Weeks
Authors: Staboulidou Ismini , Pereira Susana , de Jesus Cruz Jader , Syngelaki Argyro , Nicolaides Kypros H.
Published: August 2011

Introduction: To examine the prevalence and outcome of absent ductus venosus (DV) diagnosed at 11–13 weeks’ gestation. Method: Prospective screening study for aneuploidies in 65,840 singleton pregnancies, including measurement of nuchal translucency (NT) thickness and examination of the DV. Prenatal findings and outcome of fetuses with absent DV were examined. Results: Absent DV was diagnosed in 26 cases giving a prevalence of 1 in 2,532. In 15 (57.7%) cases the NT was above the 95th centile for crown-rump length. In 11 (42.3%) cases, there was an aneuploidy, mainly Turner syndrome. The incidence of aneuploidies was 66.7% (10 of 15) for those with NT above the 95th centile and 9.1% (1 of 11) in those with normal NT (p = 0.015). In addition to the aneuploidies, there were 3 cases with other abnormalities, including one case each of Ebstein anomaly, Noonan syndrome and Pierre Robin sequence. In 9 of the 11 (81.8%) fetuses with NT below the 95th centile, absent DV was an isolated finding and the pregnancies resulted in healthy live births. Conclusion: The prognosis of fetuses with absent DV depends on the measurement of NT thickness, being poor if the NT is increased and good if the NT is normal.
Contribution of Method of Conception on Pregnancy Outcome after the 11–13 Weeks Scan
Authors: Chaveeva Petya , Carbone Ilma F. , Syngelaki Argyro , Akolekar Ranjit , Nicolaides Kypros H.
Published: August 2011

Objective: To examine the effect of method of conception on adverse pregnancy outcome after the 11–13 weeks scan. Methods: Prospective screening study for adverse obstetric outcomes in women with singleton pregnancies and live fetus with no obvious defects at 11+0–13+6 weeks. The method of conception was recorded as spontaneous, in vitro fertilization (IVF) and assisted by ovulation induction (OI) drugs without IVF. Regression analysis was performed to examine the association between the method of conception and pregnancy outcome after adjustment for maternal characteristics. Results: In the study population of 41,577 pregnancies, conception was spontaneous in 40,261 (96.9%), by IVF in 634 (1.5%) and by OI in 682 (1.6%). In the pregnancies conceived by assisted reproductive technology, compared to spontaneous conceptions, there was a higher risk of stillbirth, pre-eclampsia, gestational hypertension, gestational diabetes mellitus, delivery of small for gestational age neonates and caesarean section. However, multiple regression analysis showed that after taking into account maternal characteristics, the only significant contributions of IVF were for pre-eclampsia and elective caesarean section and the contributions of OI were for miscarriage, spontaneous early preterm delivery and small for gestational age. Conclusions: Conception by IVF and OI is associated with increased risk for adverse pregnancy outcome.
Regulatory T Cells Control Type I Food Allergy to Beta-Lactoglobulin in Mice
Authors: Kanjarawi Reem , Dercamp Christophe , Etchart Nathalie , Adel-Patient Karine , Nicolas Jean-François , Dubois Bertrand , Kaiserlian Dominique
Published: August 2011

Background: Regulatory T cells contribute to peripheral immune tolerance, yet their ability to control immediate-type hypersensitivity (ITH) reactions involved in IgE-mediated food allergy is still poorly documented. Objectives: We investigated in mice whether CD4+CD25+ regulatory T cells could control ITH to β-lactoglobulin (BLG), a major allergen in cow’s milk. Methods: C3H/HeOuJ mice were sensitized by repeated oral gavage with BLG plus cholera toxin as adjuvant and orally challenged with BLG alone to elicit allergic symptoms. Mice were treated with the anti-CD25 mAb (PC61) before sensitization. Oral sensitization (afferent phase of ITH) was assessed by production of BLG-specific serum antibodies and Th1/Th2-type cytokines by specific CD4+ T cells in mesenteric lymph nodes. ITH was elicited by oral BLG challenge (efferent phase of ITH) and we monitored symptom scores, numbers and function of intestinal mast cells and serum level of the mucosal mast cell protease mMCP-1. Results: Upon oral BLG challenge, orally sensitized mice developed only mild clinical signs. Anti-CD25 mAb-treated mice exhibited enhancement of both BLG-specific CD4+ T cell priming with IL-4, IL-5, IL-13 and IFN-γ production and total IgE, and BLG-specific IgE, IgG1 and IgG2a in serum. Anti-CD25 mAb treatment caused more severe symptoms upon BLG challenge, which correlated with enhanced serum levels of the mucosal mast cell protease mMCP-1. Conclusions: These data document that constitutive CD4+CD25+ regulatory T cells alleviate clinical signs of ITH to dietary BLG by modulating the priming of BLG-specific T and B cell responses during oral sensitization and enhancing mast cell degranulation.
Are Serum Protein Biomarkers Derived from Proteomic Analysis Useful in Screening for Trisomy 21 at 11–13 Weeks?
Authors: Mastricci Anna Lucia , Akolekar Ranjit , Kuppusamy Ramesh , Ahmed Mustafa , Nicolaides Kypros H.
Published: August 2011

Objective: The aim of this study is to identify potential biomarkers for fetal trisomy 21 from previous publications using proteomic techniques and examine the potential value of such biomarkers in early screening for this aneuploidy. Methods: This was a case-control study of 25 pregnancies with fetal trisomy 21 and 50 euploid controls undergoing first-trimester screening for aneuploidies by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free β-human chorionic gonadotrophin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A). The maternal serum concentrations of afamin, apolipoprotein E, clusterin, ceruloplasmin, epidermal growth factor, fetuin-A, pigment epithelium-derived factor glycoprotein and transthyretin were determined using an ELISA and compared in the euploid and trisomy 21 groups. Results: In pregnancies with fetal trisomy 21, the median maternal age, fetal NT thickness and serum free β-hCG were increased, whereas serum PAPP-A was decreased. However, there were no significant differences between cases and controls in any of the biomarkers. Conclusion: Proteins identified as potential biomarkers for trisomy 21 using proteomic techniques have not been found to be useful in early screening for this aneuploidy.
Pru p 3-Sensitised Italian Peach-Allergic Patients Are Less Likely to Develop Severe Symptoms When Also Presenting IgE Antibodies to Pru p 1 and Pru p 4
Authors: Pastorello Elide A. , Farioli Laura , Pravettoni Valerio , Scibilia Joseph , Mascheri Ambra , Borgonovo Linda , Piantanida Marta , Primavesi Laura , Stafylaraki Chrysi , Pasqualetti Sara , Schroeder Jan , Nichelatti Michele , Marocchi Alessandro
Published: August 2011

Background: The roles played by different peach allergens with respect to symptom severity have not been completely ascertained. We have evaluated the diagnostic efficacy of peach recombinant allergens ImmunoCAP compared to peach in the identification of subjects at an increased risk for severe reactions to peaches. Methods: 148 peach-allergic patients were divided based on their symptom severity into 2 groups: mild oral allergy syndrome (OAS) and severe OAS. Anti-rPru p 1, 3 and 4 IgE levels were measured. Statistical analyses were carried out using parametric and non-parametric tests. Results: anti-rPru p 1 and anti-rPru p 4 IgE levels were significantly higher in patients with mild OAS than in patients with severe OAS (p = 0.0001); in contrast, anti-rPru p 3 IgE levels were significantly higher in patients with severe OAS than in patients with mild OAS (p < 0.00005). Moreover, we found that any unitary increase in anti-rPru p 1 IgE values corresponded to a 2.48% reduction in the odds of having severe OAS (p = 0.048), whereas any unitary increase in anti-rPru p 3 IgE values corresponded to a 9.02% increase in the probability of having severe OAS (p = 0.001). Unexpectedly, we found that patients positive to rPru p 3 as well as rPru p 1 and 4 demonstrated a significant reduction of the odds of developing severe symptoms than those positive to rPru p 3 alone. Anti-rPru p 3 IgE levels were a significantly better indicator than anti-peach IgE values (p = 0.016) of patients with the highest risk for severe OAS. A cutoff of 2.69 kUA/l for anti-rPru p 3 IgE values better discriminated peach-allergic patients at a higher risk for symptoms. Conclusions: Italian patients with positive anti-rPru p 1, 4 and 3 IgE levels seemed less likely to experience the clinical effects of high anti-rPru p 3 IgE values.
Effect of Instant Controlled Pressure Drop on IgE Antibody Reactivity to Peanut, Lentil, Chickpea and Soybean Proteins
Authors: Cuadrado Carmen , Cabanillas Beatriz , Pedrosa Mercedes M. , Muzquiz Mercedes , Haddad Joseph , Allaf Karim , Rodriguez Julia , Crespo Jesus F. , Burbano Carmen
Published: August 2011

Background: The use of legume seeds is being expanded in the food industry due to their excellent nutritional and technological properties. However, legumes have been considered causative agents of allergic reactions through ingestion. Previous studies indicated that processing methods combining heat and steam pressure, such as instant controlled pressure drop (DIC®), could decrease allergenicity. The aim of this study was to investigate the impact of DIC treatment on peanut, lentil, chickpea and soybean IgE antibody reactivity. Methods: Peanut, lentil, chickpea and soybeanseeds were subjected to DIC treatment at different pressure and time conditions (3 and 6 bar for 1 and 3 min). Control (raw) and DIC-treated extracts were analyzed by SDS-PAGE and immunoblotting using a serum pool from sensitized patients. Results: DIC treatment did not affect the total protein content of legume seeds. Nevertheless, modifications of protein profiles after DIC showed a general decrease in IgE binding to legume proteins that was correlated to a higher steam pressure and longer treatment. The immunoreactivity of soybean proteins was almost abolished with treatment at 6 bar for 3 min. Conclusions: The results demonstrated that DIC treatment produces a reduction in the overall in vitro IgE binding of peanut, lentil and chickpea and a drastic reduction in soybean immunoreactivity.
Molecular Pathogenesis of Hepatocellular Carcinoma: Altering Transforming Growth Factor-β Signaling in Hepatocarcinogenesis
Authors: Yamazaki Ken , Masugi Yohei , Sakamoto Michiie
Published: August 2011

Hepatocellular carcinoma (HCC) occurs subsequent to liver injury, where regenerative hepatocytes develop into a dysplastic nodule and then early HCC, supporting the multistep hepatocarcinogenesis theory. Molecular alterations such as the p53 mutation, p16 gene silencing, and AKT signaling activation are found in the late stage of HCC progression. The overexpression of some marker molecules is observed at the early stage. Transforming growth factor-β (TGF-β), a potent inhibitor of cell proliferation, is frequently overexpressed in HCC, although the role of TGF-β signaling during HCC development remains controversial. We previously reported that HCC cells show TGF-β receptor-dependent growth inhibition in response to TGF-β. Also, reduced TGF-β receptor II in HCC correlates with intrahepatic metastasis and shorter time-to-recurrence, suggesting a role of TGF-β signaling in tumor suppression. In contrast, TGF-β overexpression in HCC is known to correlate with malignant potential, suggesting a role in tumor promotion. Enhanced formation of stroma is a feature of advanced HCC, and TGF-β also promotes the proliferation of stromal fibroblasts. The microenvironment produced via tumor-stromal interactions may be the key to the modulation of the dual roles of TGF-β signaling in HCC progression.
Des-γ-Carboxyprothrombin May Be a Promising Biomarker to Determine the Therapeutic Efficacy of Sorafenib for Hepatocellular Carcinoma
Authors: Ueshima Kazuomi , Kudo Masatoshi , Takita Masahiro , Nagai Tomoyuki , Tatsumi Chie , Ueda Taisuke , Kitai Satoshi , Ishikawa Emi , Yada Norihisa , Inoue Tatsuo , Hagiwara Satoru , Minami Yasunori , Chung Hobyung , Sakurai Toshiharu
Published: August 2011

Objective: The purpose of this study was to evaluate the role of des-γ-carboxyprothrombin (DCP) as a marker for the efficacy of sorafenib therapy for hepatocellular carcinoma (HCC). Methods: Patients with advanced HCC treated with sorafenib were retrospectively evaluated, focusing on DCP levels and clinical characteristics. Results: 50 patients with advanced HCC were treated with sorafenib alone. In 25 of these patients, the serum levels of DCP were evaluated twice (pretreatment and within 2 weeks after starting therapy). The time to progression was significantly longer in patients in whom the DCP level at 2 weeks after starting sorafenib was ≧2-fold higher than the pretreatment levels, as compared with patients without an increase in DCP (p = 0.0296). Conclusions: The serum level of DCP is a surrogate marker for tissue hypoxia and can be a predictive marker to assess the tumor response to sorafenib therapy.
In vivo and in vitro Examination of the Tendinous Inscription of the Human Semitendinosus Muscle
Authors: Kellis Eleftherios , Galanis Nikiforos , Natsis Konstantinos , Kapetanos George
Published: August 2011

The aim of this study was to examine the tendinous inscription (TI) of the human semitendinosus (ST) muscle using dissection (cadavers) and ultrasound (in vivo). Ultrasonography (US) scans were taken in 18 young males at rest and at maximum voluntary contraction (MVC). Further, the ST was dissected and removed from its origins in 10 cadaveric specimens (5 cadavers). The cadaveric long arm of the TI was 6.67 ± 0.64 cm (6.45 ± 1.21 in US) while the shorter arm was 2.39 ± 0.38 cm (1.99 ± 0.75 in US). The angle formed by the two TI arms ranged from 53.19 (US) to 56.05° (cadavers) while more superficial fascicles intersected the inscription at significantly higher angles (range 31.98 ± 6.15 to 34.69 ± 7.71°) compared with deeper fascicles (p < 0.05). Fascicle length did not differ between compartments, but it was significantly smaller in superficial compared with deeper layers (p < 0.05). With the exception of the angle between the TI arm and the deep aponeurosis, all measured angles as well as the length of the long arm of the TI increased significantly from rest to MVC (p < 0.05). The role of the TI probably lies in the local interconnections with the fascicles of either compartment, which upon contraction is such that the ST muscle contracts as one muscle. However, the TI arm morphology changes from rest to MVC, indicating a nonuniform displacement of the TI, mainly between the superficial and deeper layers of the muscle.
Growing Bacteria Shed Elicitors of Drosophila Humoral Immunity
Authors: Karlsson Jenny , Oldenvi Sandra , Fahlander Carina , Daenthanasanmak Anusara , Steiner Håkan
Published: August 2011

It has been much debated how the Drosophila immune system can recognize bacterial peptidoglycan that is often hidden. We show that bacteria separated from Drosophila S2 cells by a semipermeable membrane can upregulate the Imd pathway. Supernatants from exponentially growing but not from stationary-phase bacterial cultures induce antimicrobial peptides. It is also made likely that the shed elicitors are of peptidoglycan nature.
Is Extracellular Volume Expansion of Peritoneal Dialysis Patients Associated with Greater Urine Output?
Authors: Davenport Andrew , Sayed Rabya Hussain , Fan Stanley
Published: August 2011

Background and Objectives: Residual renal function (RRF) is important for peritoneal dialysis (PD) technique failure and patient survival. Reduction in extracellular water (ECW) has been reported to reduce urine output. We audited volume status and RRF to determine whether ECW was linked to urinary output. Methods: We retrospectively audited PD patients who had RRF and multiple frequency bioimpedance spectroscopy assessments. Results: 550 patients were studied. Urine output was lower in males (p = 0.021), non-Caucasoids (p = 0.04), those prescribed antihypertensives (p < 0.001), and greater glucose dialysate usage (p < 0.001). Urine output was negatively associated with dialysis vintage (F = 40.7, β –0.627, p < 0.001), and ECW (F = 33.7, β –0.177, p < 0.001) and positively associated with intracellular volume (F = 34.6, β 0.11, p < 0.001). Conclusions: RRF is important for successful PD, and ECW volume expansion may lead to better preservation of RRF in PD patients compared to haemodialysis. However, in our retrospective cross-sectional study, ECW expansion was associated with reduced urine output.
Interleukin-18 Promoter Polymorphism and Development of Antibodies to Surface Antigen of Hepatitis B Virus in Hemodialysis Patients
Authors: Grzegorzewska Alicja E. , Wobszal Piotr , Jagodziński Paweł P.
Published: August 2011

Background: Interleukin (IL)-18 is involved in hepatitis B virus (HBV) clearance and augments antibodies against surface antigen of HBV (anti-HBsAg) production during DNA vaccination. The IL-18 –1297C>T (rs360719) polymorphism may modulate the IL-18 expression. Aim: To determine the potential association of IL-18 –1297C>T polymorphism with development of anti-HBsAg in hemodialysis (HD) patients. Methods: The frequency of IL-18 –1297C>T alleles and genotypes was identified by polymerase chain reaction restriction fragment length polymorphism in 435 HD patients. Group 1 (n = 219) developed an anti-HBsAg titer >10 IU/l as a result of vaccination or HBV transmission. Group 2 (n = 216) included patients who did not develop an anti-HBsAg titer >10 IU/l in response to at least one full series of vaccination or HBV transmission. The significance of genotype frequency was tested using the Fisher exact test. Results: In group 1, the frequencies of –1297CC, –1297CT and –1297TT genotypes were 7.3, 39.7 and 53.0%, respectively, and in group 2 they were 1.9, 42.1 and 56.0%, respectively. The odds ratio for CC versus CT + TT was 0.239 (95% CI 0.079–0.728, p = 0.010), and for CC versus TT it was 0.240 (95% CI 0.078–0.738, p = 0.009). Conclusion: In HD patients, the IL-18 –1297CC genotype may play a role in anti-HBsAg development in response to HBV surface antigen.
Trefoil Factor 3 Predicts Incident Chronic Kidney Disease: A Case-Control Study Nested within the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Astor Brad C. , Köttgen Anna , Hwang Shih-Jen , Bhavsar Nrupen , Fox Caroline S. , Coresh Josef
Published: August 2011

Background: Early detection of individuals at high risk for chronic kidney disease (CKD) may aid prevention. Urinary levels of trefoil factor 3 (TFF3) are associated with acute kidney injury in animal models, but the association of TFF3 levels with incident CKD in humans is unknown. Methods: We conducted a case-control study nested within the Atherosclerosis Risk in Communities (ARIC) Study and the ARIC Carotid MRI Study to determine whether urinary TFF3 levels predict incident CKD over 8.6 years of follow-up. A total of 143 participants with incident CKD (eGFR decreasing by ≧25% to <60 ml/min/1.73 m2) were matched on age, sex and race to 143 non-cases. Results: Higher TFF3 levels at baseline were strongly associated with Black race, diabetes (both p = 0.002), and antihypertensive medication use (p = 0.02). Compared to participants with TFF3 levels in the lowest quartile, the odds ratio (OR) of incident CKD was 1.84 (95% confidence interval (CI): 0.80, 4.22) for individuals with TFF3 levels in the second quartile, 2.43 (95% CI: 1.06, 5.53) for the third quartile, and 2.77 (95% CI: 1.22, 6.28) for the fourth quartile (p trend = 0.02). Adjustment for covariates, including urinary albumin: creatinine ratio, did not markedly change the associations. Twofold higher TFF3 levels were strongly associated with incident CKD after adjustment for CKD risk factors (adjusted OR = 1.35; 95% CI: 1.11, 1.64). Conclusions: Higher urinary TFF3 levels may indicate ongoing repair of damage in the kidney. Additional studies are needed to confirm whether TFF3 can be useful as a marker of increased risk for CKD.
Carvedilol Ameliorates Low-Turnover Bone Disease in Non-Obese Type 2 Diabetes
Authors: Goto Shunsuke , Fujii Hideki , Kono Keiji , Nakai Kentaro , Hamada Yasuhiro , Yamato Hideyuki , Shinohara Masami , Kitazawa Riko , Kitazawa Sohei , Nishi Shinichi , Fukagawa Masafumi
Published: August 2011

Background: Diabetic bone disease is a major complication in diabetes mellitus and is characterized by low-turnover bone formation. Recent studies have demonstrated that oxidative stress could be associated with diabetic bone disease and that β-adrenergic antagonists could increase bone formation. Our study investigated the effect of carvedilol (β-blocker), possessing an antioxidant effect, on diabetic bone disease. Methods: We used the non-obese, type 2 diabetes model Spontaneously Diabetic Torii (SDT) rats in this study. Sprague-Dawley rats were used as controls (control, n = 6). SDT rats were divided into four groups: diabetic (DM, n = 8), DM+insulin (DM+I, n = 7), DM+carvedilol (DM+C, n = 8), and DM+N-acetylcysteine (DM+N, n = 10) at 20 weeks. The rats were sacrificed at 30 weeks, after which blood and urine samples, bone mineral density, histomorphometry, and oxidative stress were evaluated. Results: The number of 8-hydroxydeoxyguanosine-positive cells in bone tissue was significantly lower in the DM+C and DM+N groups than in the DM group. Mineral apposition rate and bone formation rate per bone surface in the DM+C and DM+N groups were significantly higher than those in the DM group, and these parameters were better in the DM+C group than in the DM+N group. Conclusion: Our data suggest that carvedilol has stronger effects on diabetic low-turnover bone disease beyond that which can be attributed to its antioxidative stress mechanism.
Arteriogenic Therapy by Intramyocardial Sustained Delivery of a Novel Growth Factor Combination Prevents Chronic Heart Failure
Authors: Banquet Sébastien , Gomez Elodie , Nicol Lionel , Edwards-Lévy Florence , Henry Jean-Paul , Cao Renhai , Schapman Damien , Dautreaux Brigitte , Lallemand Francoise , Bauer Fabrice , Cao Yihai , Thuillez Christian , Mulder Paul , Richard Vincent , Brakenhielm Ebba
Published: August 2011

Background—

Therapeutic angiogenesis is a promising approach for the treatment of cardiovascular diseases, including myocardial infarction and chronic heart failure. We aimed to improve proangiogenic therapies by identifying novel arteriogenic growth factor combinations, developing injectable delivery systems for spatiotemporally controlled growth factor release, and evaluating functional consequences of targeted intramyocardial growth factor delivery in chronic heart failure.

Methods and Results—

First, we observed that fibroblast growth factor and hepatocyte growth factor synergistically stimulate vascular cell migration and proliferation in vitro. Using 2 in vivo angiogenesis assays (n=5 mice per group), we found that the growth factor combination results in a more potent and durable angiogenic response than either growth factor used alone. Furthermore, we determined that the molecular mechanisms involve potentiation of Akt and mitogen-activated protein kinase signal transduction pathways, as well as upregulation of angiogenic growth factor receptors. Next, we developed crosslinked albumin-alginate microcapsules that sequentially release fibroblast growth factor-2 and hepatocyte growth factor. Finally, in a rat model of chronic heart failure induced by coronary ligation (n=14 to 15 rats per group), we found that intramyocardial slow release of fibroblast growth factor-2 with hepatocyte growth factor potently stimulates angiogenesis and arteriogenesis and prevents cardiac hypertrophy and fibrosis, as determined by immunohistochemistry, leading to improved cardiac perfusion after 3 months, as shown by magnetic resonance imaging. These multiple beneficial effects resulted in reduced adverse cardiac remodeling and improved left ventricular function, as revealed by echocardiography.

Conclusion—

Our data showing the selective advantage of using fibroblast growth factor-2 together with hepatocyte growth factor suggest that this growth factor combination may constitute an efficient novel treatment for chronic heart failure.