bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination of hTERT Knockdown and IFN-γ Treatment Inhibited Angiogenesis and Tumor Progression in Glioblastoma
Authors: George Joseph , Banik Naren L. , Ray Swapan K.
Published: November 2009

Purpose: The limitless invasive and proliferative capacities of tumor cells are associated with telomerase and expression of its catalytic component, human telomerase reverse transcriptase (hTERT). IFN-γ modulates several cellular activities, including signaling pathways and cell cycle, through transcriptional regulation.

Experimental Design: Using a recombinant plasmid with hTERT siRNA cDNA, we downregulated hTERT during IFN-γ treatment in human glioblastoma SNB-19 and LN-18 cell lines and examined whether such a combination could inhibit angiogenesis and tumor growth in nude mice. In vitro angiogenesis assay was done using coculture of tumor cells with human microvascular endothelial cells. In vivo angiogenesis assay was done using diffusion chambers under the dorsal skin of nude mice. In vivo imaging of intracerebral tumorigenesis and longitudinal solid tumor development studies were conducted in nude mice.

Results: In vitro and in vivo angiogenesis assays showed inhibition of capillary-like network formation of microvascular endothelial cells and neovascularization under dorsal skin of nude mice, respectively. We observed inhibition of intracerebral tumorigenesis and s.c. solid tumor formation in nude mice after treatment with combination of hTERT siRNA and IFN-γ. Western blotting of solid tumor samples showed significant downregulation of the molecules that regulate cell invasion, angiogenesis, and tumor progression.

Conclusions: Our study showed that the combination of hTERT siRNA and IFN-γ effectively inhibited angiogenesis and tumor progression through the downregulation of molecules involved in these processes. Therefore, the combination of hTERT siRNA and IFN-γ is a promising therapeutic strategy for controlling the growth of human glioblastoma. (Clin Cancer Res 2009;15(23):7186–95)
Phase I Study of Flavopiridol with Oxaliplatin and Fluorouracil/Leucovorin in Advanced Solid Tumors
Authors: Rathkopf Dana , Dickson Mark A. , Feldman Darren R. , Carvajal Richard D. , Shah Manish A. , Wu Nian , Lefkowitz Robert , Gonen Mithat , Cane Lauren M. , Dials Heather J. , Winkelmann Jennifer L. , Bosl George J. , Schwartz Gary K.
Published: November 2009

Purpose: Flavopiridol, a cyclin-dependent kinase inhibitor, has promising clinical activity when combined with chemotherapy. Preclinical data indicate that flavopiridol enhances oxaliplatin- and fluorouracil (5FU)–induced apoptosis in a sequence-dependent manner.

Experimental Design: We conducted a phase I trial of flavopiridol + FOLFOX (folinic acid, 5FU, and oxaliplatin) for advanced solid tumors. Flavopiridol was administered every 2 weeks with oxaliplatin before 5FU, based on sequence-dependent growth inhibition. Flavopiridol pharmacokinetics and p53 status were evaluated.

Results: Forty-eight patients were treated on study. With dose escalation of oxaliplatin (85 mg/m2) and 5FU (2,400 mg/m2), dose-limiting toxicities included hyponatremia, thrombocytopenia, and neutropenia. 5FU was subsequently reduced to allow for dose escalation of flavopiridol. Dose-limiting toxicities with escalation of flavopiridol were nausea, vomiting, and neutropenia. The maximum tolerated dose was 70 mg/m2 flavopiridol, 85 mg/m2 oxaliplatin, and 1,800 mg/m2 5FU continuous infusion over 48 hours. Clinical activity was noted in platinum-refractory germ cell tumors: 3 of 9 (33%) evaluable patients showed a partial response on imaging and 7 of 10 (70%) had a decline in serum tumor markers. Responses were also observed in pancreatic, gastric, and sweat gland tumors. Flavopiridol pharmacokinetics had significant interpatient variability. At the maximum tolerated dose, tumor samples were p53 mutant (>30% positive cells) for responders and p53 wild-type for nonresponders.

Conclusions: Flavopiridol with FOLFOX is a safe and tolerable regimen. Promising clinical activity was seen across tumor types. Encouraging results in the platinum-refractory germ cell tumor population has prompted a phase II trial that is currently open for accrual. (Clin Cancer Res 2009;15(23):7405–11)
Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response Criteria
Authors: Wolchok Jedd D. , Hoos Axel , O'Day Steven , Weber Jeffrey S. , Hamid Omid , Lebbé Celeste , Maio Michele , Binder Michael , Bohnsack Oliver , Nichol Geoffrey , Humphrey Rachel , Hodi F. Stephen
Published: November 2009

Purpose: Immunotherapeutic agents produce antitumor effects by inducing cancer-specific immune responses or by modifying native immune processes. Resulting clinical response patterns extend beyond those of cytotoxic agents and can manifest after an initial increase in tumor burden or the appearance of new lesions (progressive disease). Response Evaluation Criteria in Solid Tumors or WHO criteria, designed to detect early effects of cytotoxic agents, may not provide a complete assessment of immunotherapeutic agents. Novel criteria for the evaluation of antitumor responses with immunotherapeutic agents are required.

Experimental Design: The phase II clinical trial program with ipilimumab, an antibody that blocks CTL antigen-4, represents the most comprehensive data set available to date for an immunotherapeutic agent. Novel immune therapy response criteria proposed, based on the shared experience from community workshops and several investigators, were evaluated using data from ipilimumab phase II clinical trials in patients with advanced melanoma.

Results: Ipilimumab monotherapy resulted in four distinct response patterns: (a) shrinkage in baseline lesions, without new lesions; (b) durable stable disease (in some patients followed by a slow, steady decline in total tumor burden); (c) response after an increase in total tumor burden; and (d) response in the presence of new lesions. All patterns were associated with favorable survival.

Conclusion: Systematic criteria, designated immune-related response criteria, were defined in an attempt to capture additional response patterns observed with immune therapy in advanced melanoma beyond those described by Response Evaluation Criteria in Solid Tumors or WHO criteria. Further prospective evaluations of the immune-related response criteria, particularly their association with overall survival, are warranted. (Clin Cancer Res 2009;15(23):7412–20)
Telomeres: The Long and Short of Developing Non-Hodgkin Lymphoma
Authors: Noy Ariela
Published: November 2009

Chromosomal integrity is vital to the life span of the dividing cell. Telomeres are tandem sequences at chromosome ends that provide protection for the genetic coding material. Erosion of those ends leads to cell death. Does stabilization promote cancer? (Clin Cancer Res 2009;15(23):7114–5)
Targeting Histone Demethylases in Cancer Therapy
Authors: Grant Steven
Published: November 2009

A novel oligoamine analog inhibitor of histone demethylases blocks colon tumor cell growth in association with histone methylation and gene re-expression. It also markedly potentiates the activity of hypomethylating agents in vitro and in vivo, suggesting that histone demethylase inhibitors may represent a valuable addition to the armamentarium of epigenetic agents. (Clin Cancer Res 2009;15(23):7111–3)
Resistance to arginine deiminase treatment in melanoma cells is associated with induced argininosuccinate synthetase expression involving c-Myc/HIF-1α/Sp4
Authors: Tsai Wen-Bin , Aiba Isamu , Lee Soo-yong , Feun Lynn , Savaraj Niramol , Kuo Macus Tien
Published: November 2009

Arginine deiminase (ADI)–based arginine depletion is a novel strategy under clinical trials for the treatment of malignant melanoma with promising results. The sensitivity of melanoma to ADI treatment is based on its auxotrophy for arginine due to a lack of argininosuccinate synthetase (AS) expression, the rate-limiting enzyme for the de novo biosynthesis of arginine. We show here that AS expression can be transcriptionally induced by ADI in melanoma cell lines A2058 and SK-MEL-2 but not in A375 cells, and this inducibility was correlated with resistance to ADI treatment. The proximal region of the AS promoter contains an E-box that is recognized by c-Myc and HIF-1α and a GC-box by Sp4. Through ChIP assays, we showed that under noninduced conditions, the E-box was bound by HIF-1α in all the three melanoma cell lines. Under arginine depletion conditions, HIF-1α was replaced by c-Myc in A2058 and SK-MEL-2 cells but not in A375 cells. Sp4 was constitutively bound to the GC-box regardless of arginine availability in all three cell lines. Overexpressing c-Myc by transfection upregulated AS expression in A2058 and SK-MEL-2 cells, whereas cotransfection with HIF-1α suppressed c-Myc–induced AS expression. These results suggest that regulation of AS expression involves interplay among positive transcriptional regulators c-Myc and Sp4, and negative regulator HIF-1α that confers resistance to ADI treatment in A2058 and SK-MEL-2 cells. Inability of AS induction in A375 cells under arginine depletion conditions was correlated by the failure of c-Myc to interact with the AS promoter. [Mol Cancer Ther 2009;8(12):3223–33]
Celastrol Synergistically Enhances Temozolomide Cytotoxicity in Melanoma Cells
Authors: Chen Ming , Rose Amy E. , Doudican Nicole , Osman Iman , Orlow Seth J.
Published: November 2009

Efforts to improve melanoma response rates to temozolomide (TMZ) have thus far been unsuccessful. We screened a library of 2,000 marketed drugs and natural products to identify agents with the potential to sensitize melanoma cells to the effects of TMZ. Celastrol (CEL), a natural compound found in the Thunder of God vine, was identified based on its ability to enhance cell death in TMZ-resistant melanoma cells. A cell proliferation assay was used to compare the growth-inhibitory effects of TMZ alone versus TMZ/CEL combination treatment. Cytotoxic synergy was assessed using combination-index methods. The expression of nuclear factor-κB (NF-κB), IκB, mitogen-activated protein kinase, and ubiquitinated proteins were examined using Western blotting, and the localization of NF-κB in CEL-treated melanoma cells was evaluated using immunofluorescence microscopy. The CEL/TMZ combination synergistically inhibited cell proliferation in melanoma cells. CEL treatment increased the levels of ubiquitinated proteins, reduced the levels of tumor necrosis factor-α–induced IκB phosphorylation, and blocked NF-κB translocation to the nucleus. Inhibition of NF-κB with small interfering RNA mimicked the ability of CEL to sensitize melanoma cells to TMZ, suggesting that inhibition of NF-κB may play a role in TMZ/CEL-induced cytotoxicity. The TMZ/CEL combination induced the phosphorylation of c-Jun NH2-terminal kinase, implicating the mitogen-activated protein kinase pathway in the treatment effects. Our data suggest that CEL may be effective in sensitizing resistant melanoma cells to the effects of TMZ. (Mol Cancer Res 2009;7(12):1946–53)
p57KIP2: “Kip”ing the Cell under Control
Authors: Pateras Ioannis S. , Apostolopoulou Kalliopi , Niforou Katerina , Kotsinas Athanassios , Gorgoulis Vassilis G.
Published: November 2009

p57KIP2 is an imprinted gene located at the chromosomal locus 11p15.5. It is a cyclin-dependent kinase inhibitor belonging to the CIP/KIP family, which includes additionally p21CIP1/WAF1 and p27KIP1. It is the least studied CIP/KIP member and has a unique role in embryogenesis. p57KIP2 regulates the cell cycle, although novel functions have been attributed to this protein including cytoskeletal organization. Molecular analysis of animal models and patients with Beckwith-Wiedemann Syndrome have shown its nodal implication in the pathogenesis of this syndrome. p57KIP2 is frequently down-regulated in many common human malignancies through several mechanisms, denoting its anti-oncogenic function. This review is a thorough analysis of data available on p57KIP2, in relation to p21CIP1/WAF1 and p27KIP1, on gene and protein structure, its transcriptional and translational regulation, and its role in human physiology and pathology, focusing on cancer development. (Mol Cancer Res 2009;7(12):1902–19)
Lack of Evidence for Green Tea Polyphenols as DNA Methylation Inhibitors in Murine Prostate
Authors: Morey Kinney Shannon R. , Zhang Wa , Pascual Marien , Greally John M. , Gillard Bryan M. , Karasik Ellen , Foster Barbara A. , Karpf Adam R.
Published: November 2009

Green tea polyphenols (GTP) have been reported to inhibit DNA methylation in cultured cells. Here, we tested whether oral consumption of GTPs affects normal or cancer-specific DNA methylation in vivo, using mice. Wild-type (WT) and transgenic adenocarcinoma of mouse prostate (TRAMP) mice were given 0.3% GTPs in drinking water beginning at 4 weeks of age. To monitor DNA methylation, we measured 5-methyl-deoxycytidine (5mdC) levels, methylation of the B1 repetitive element, and methylation of the Mage-a8 gene. Each of these parameters were unchanged in prostate, gut, and liver from WT mice at both 12 and 24 weeks of age, with the single exception of a decrease of 5mdC in the liver at 12 weeks. In GTP-treated TRAMP mice, 5mdC levels and the methylation status of four loci hypermethylated during tumor progression were unaltered in TRAMP prostates at 12 or 24 weeks. Quite surprisingly, GTP treatment did not inhibit tumor progression in TRAMP mice, although known pharmacodynamic markers of GTPs were altered in both WT and TRAMP prostates. We also administered 0.1%, 0.3%, or 0.6% GTPs to TRAMP mice for 12 weeks and measured 5mdC levels and methylation of B1 and Mage-a8 in prostate, gut, and liver tissues. No dose-dependent alterations in DNA methylation status were observed. Genome-wide DNA methylation profiling using the HpaII tiny fragment enrichment by ligation-mediated PCR assay also revealed no significant hypomethylating effect of GTP. These data indicate that oral administration of GTPs does not affect normal or cancer-specific DNA methylation in the murine prostate.
Dietary Tricin Suppresses Inflammation-Related Colon Carcinogenesis in Male Crj: CD-1 Mice
Authors: Oyama Takeru , Yasui Yumiko , Sugie Shigeyuki , Koketsu Mamoru , Watanabe Kunitomo , Tanaka Takuji
Published: November 2009

The flavone 4′,5,7-trihydroxy-3′,5′-dimethoxyflavone (tricin) present in rice, oats, barley, and wheat exhibits antigrowth activity in several human cancer cell lines and anti-inflammatory potential. However, the chemopreventive activity has not yet been elucidated in preclinical animal models of colorectal cancer. This study was designed to determine whether dietary tricin exerts inflammation-associated colon carcinogenesis induced by azoxymethane and dextran sulfate sodium in mice. Male Crj: CD-1 mice were initiated with a single i.p. injection of azoxymethane (10 mg/kg body weight) and followed by a 1-week exposure to dextran sulfate sodium (1.5%, w/v) in drinking water to induce colonic neoplasms. They were then given the experimental diet containing 50 or 250 ppm tricin. The experiment was terminated at week 18 to determine the chemopreventive efficacy of tricin. In addition, the effects of dietary tricin on the expression of several inflammatory cytokines, including tumor necrosis factor (TNF)-α, were assayed. The development of colonic adenomas and adenocarcinomas was significantly reduced by feeding with 50 and 250 ppm tricin, respectively. Dietary tricin also significantly reduced the proliferation of adenocarcinoma cells as well as the numbers of mitoses/anaphase bridging in adenocarcinoma cells. The dietary administration with tricin significantly inhibited the expression of TNF-α in the nonlesional cypts. Our findings that dietary tricin inhibits inflammation-related mouse colon carcinogenesis by suppressing the expression of TNF-α in the nonlesional cyrpts and the proliferation of adenocarcinomas suggest a potential use of tricin for clinical trials of colorectal cancer chemoprevention.
EphA2 in the Early Pathogenesis and Progression of Non–Small Cell Lung Cancer
Authors: Brannan Jennifer M. , Sen Banibrata , Saigal Babita , Prudkin Ludmila , Behrens Carmen , Solis Luisa , Dong Wenli , Bekele B. Nebiyou , Wistuba Ignacio , Johnson Faye M.
Published: November 2009

Overexpression of the receptor tyrosine kinase EphA2 occurs in non–small cell lung cancer (NSCLC) and a number of other human cancers. This overexpression correlates with a poor prognosis, smoking, and the presence of Kirsten rat sarcoma (K-Ras) mutations in NSCLC. In other cancers, EphA2 has been implicated in migration and metastasis. To determine if EphA2 can promote NSCLC progression, we examined the relationship of EphA2 with proliferation and migration in cell lines and with metastases in patient tumors. We also examined potential mechanisms involving AKT, Src, focal adhesion kinase, Rho guanosine triphosphatases (GTPase), and extracellular signal–regulated kinase (ERK)-1/2. Knockdown of EphA2 in NSCLC cell lines decreased proliferation (colony size) by 20% to 70% in four of five cell lines (P < 0. 04) and cell migration by 7% to 75% in five of six cell lines (P < 0. 03). ERK1/2 activation correlated with effects on proliferation, and inhibition of ERK1/2 activation also suppressed proliferation. In accordance with the in vitro data, high tumor expression of EphA2 was an independent prognostic factor in time to recurrence (P = 0.057) and time to metastases (P = 0.046) of NSCLC patients. We also examined EphA2 expression in the putative premalignant lung lesion, atypical adenomatous hyperplasia, and the noninvasive bronchioloalveolar component of adenocarcinoma because K-Ras mutations occur in atypical adenomatous hyperplasia and are common in lung adenocarcinomas. Both preinvasive lesion types expressed EphA2, showing its expression in the early pathogenesis of lung adenocarcinoma. Our data suggest that EphA2 may be a promising target for treating and preventing NSCLC.
Preventive Effects of Bexarotene and Budesonide in a Genetically Engineered Mouse Model of Small Cell Lung Cancer
Authors: Wang Yian , Wen Weidong , Yi Yijun , Zhang Zhongqiu , Lubet Ronald A. , You Ming
Published: November 2009

In the present study, we examined the effect of bexarotene (Targretin) and budesonide in the chemoprevention of small cell lung carcinoma using a lung-specific knockout model of Rb1 and p53. Upon treatment with bexarotene, tumor incidence, number, and load were significantly reduced (P < 0.05). Budesonide treatment trended to inhibition, but the effect was not statistically significant (P > 0.05). Immunohistochemical staining indicated that bexarotene treatment decreased cell proliferation and increased apoptosis in tumors. The Rb1/p53 gene–targeted mouse seems to be a valuable model for chemopreventive studies on human small cell lung cancer. Our results indicate that the retinoid X receptor agonist bexarotene may be a potent chemopreventive agent in this cancer type.
Effects of Extracellular Matrix on Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Smooth Muscle Cell Lineage: Utility for Cardiovascular Tissue Engineering
Authors: Suzuki Shuichi , Narita Yuji , Yamawaki Aika , Murase Yosuke , Satake Makoto , Mutsuga Masato , Okamoto Hideki , Kagami Hideaki , Ueda Minoru , Ueda Yuichi
Published: November 2009

Background: Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into various types of cell, and the extracellular matrix (ECM) is acknowledged to be important for the regulation of cell functions. In this study, we demonstrated the effects of ECMs on the differentiation of human bone marrow-derived MSCs into a smooth muscle cell (SMC) lineage. Methods: Human MSCs (hMSCs) were cultured on dishes coated with 3 types of ECM including laminin (LM), collagen type IV (Col-IV) and fibronectin for 7 days, and simultaneously cultured on a noncoated dish as a control. Cell numbers of these cultured hMSCs were counted, and their expression of SMC-specific genes and proteins was evaluated. hMSCs were then seeded on LM-coated biodegradable sheets and implanted into rat subcutaneous space. After 2 weeks of implantation, these tissues were evaluated. Results: The number of hMSCs was significantly increased by culture on Col-IV-coated dishes. The expression of SMC-specific genes and proteins (α-smooth muscle actin, ASMA; h1-calponin, CALP) in hMSC was significantly upregulated from culture on LM-coated dishes. LM-coated sheets showed a significantly increased expression of ASMA and CALP protein in vivo. Moreover, a fully differentiated marker (SM2) was expressed in the in vivo implanted hMSCs in the course of 2 weeks on the LM-coated sheet. Conclusion: These results suggest that the signal transduction of the cell-matrix interaction for the differentiation of hMSCs into SMCs was activated when cultured with LM. LM-coated materials may thus be useful for cardiovascular tissue engineering.
Dynamic Expression and Heterogeneous Intracellular Location of En-1 during Late Mouse Embryonic Development
Authors: Zhong Shan-chuan , Chen Xing-shu , Cai Qi-yan , Luo Xue , Chen Xing-hua , Liu Jing , Yao Zhong-xiang
Published: November 2009

Engrailed-1 (En-1) is a transcription factor involved in the development of the midbrain/hindbrain during mouse early embryogenesis. Although En-1 is expressed from embryogenesis to adulthood, there has been no detailed description of its expression during late mouse embryonic development. Here we report the expression pattern of En-1 in the mouse embryo from E10.5 to the neonatal state. With immunohistochemistry we found that En-1 was expressed in the central nervous system (CNS) from E10.5 to the neonatal state, mostly restricted to the midbrain/hindbrain junction. Outside the CNS, En-1 is dynamically expressed in several neural crest-associated structures including the cranial mesenchyme, the mandibular arches, the vagus nerve, the dorsal root ganglia, the sympathetic ganglia, the somites, the heart and the cloaca. Additionally, we found that in the CNS, most of the En-1 was located in the nuclei, while outside the CNS, En-1 was mainly expressed in the cytoplasm. These findings provided additional evidence that En-1 may be involved in the development of neural crest cells.
Expression of Cyclooxygenase-2 in Eutopic Endometrium and Ovarian Endometriotic Tissue in Women with Severe Endometriosis
Authors: Cho SiHyun , Park Soo Hyeon , Choi Young Sik , Seo Seok Kyo , Kim Hye Yeon , Park Ki Hyun , Cho Dong Jae , Lee Byung Seok
Published: November 2009

Background/Aims: The purpose of this study is to evaluate the level and pattern of cyclooxygenase-2 (Cox-2) expression in endometriosis and to investigate the correlation between the expression of Cox-2 and several clinicosurgical parameters. Methods: Twenty-six patients with endometriosis and 21 patients with other benign gynecological conditions were enrolled. The eutopic endometrium was sampled by pipelle, and fragments of ovarian endometrioma and non-endometriotic ovarian cysts were sampled during surgery. Total RNA isolation and semiquantitative reverse transcriptase polymerase chain reaction was performed. Results: The expression of Cox-2 mRNA (mean ± SEM) in eutopic endometrium and ovarian endometriotic tissue significantly increased in patients with endometriosis compared with the controls. The expression of Cox-2 increased significantly in the proliferative phase in eutopic endometrium and in the secretory phase in ovarian endometriotic tissue of patients with endometriosis compared with the controls. Cox-2 mRNA expression in the endometrium and ovarian lesions significantly correlated with serum CA-125 and the diameter of the endometrioma. Conclusions: Cox-2 expression increased in the eutopic endometrium and ovarian endometriotic tissue of the patients with endometriosis. These findings indicate that Cox-2 may be involved in the pathogenesis and progression of endometriosis.
Effect of Oxygen on the Expression of Hypoxia-Inducible Factors in Human Fetal Lung Explants
Authors: Rajatapiti Prapapan , de Rooij Jessica D. , Beurskens Leonardus W.J.E. , Keijzer Richard , Tibboel Dick , Rottier Robbert J. , de Krijger Ronald R.
Published: November 2009

Background: Fetal lung development requires proper coordination between lung epithelial and vascular morphogenesis. A major determinant in lung vascular development is vascular endothelial growth factor (VEGF), which is regulated by hypoxia-inducible factors (HIFs). VEGF is expressed in the airway epithelium, while its receptors (VEGFRs) are expressed in the pulmonary mesenchyme. The hypoxic environment in utero is beneficial for fetal organogenesis, especially vascular development. However, little is known about the expression of HIFs and VEGFR-2 in the human fetal lung in vitro. Objectives: The purpose of this study was to investigate the effects of hypoxia on fetal lung morphology and mRNA expression of VEGF, VEGFR-2, HIF-2α, and HIF-3α. Methods: An explant culture technique was used to study the effects of normoxic and hypoxic conditions on human fetal lung. Results: The morphology remained largely unchanged in explants cultured under hypoxic or normoxic conditions. Quantitative RT-PCR showed that the mRNA expression of VEGF-A, but not VEGFR-2 is upregulated in explants cultured at 1.5% compared with 21% oxygen. We observed a nonsignificant increase in HIF-2α and HIF-3α mRNA expression in explants cultured at 1.5% oxygen. These data suggest that the mRNA expression of VEGF, and possibly HIF-2α and HIF-3α, is regulated by hypoxia in the developing human lung. Conclusion: This lung explant culture model appears to be a valuable model to unravel the molecular mechanisms of human lung development.
Spectroscopic Noninvasive Measurement of Hemoglobin Compared with Capillary and Venous Values in Neonates
Authors: Rabe H. , Fernandez Alvarez R. , Whitfield T. , Lawson F. , Jungmann H.
Published: November 2009

Background: Venepuncture-related blood loss is a common cause of neonatal anemia. Currently, this is the only way to obtain hemoglobin levels. This causes distress for the infant but can also lead to the need for blood transfusions. Recently, a new technique for measuring hemoglobin levels non-invasively has been developed to reduce iatrogenic blood loss and pain. Objective: To compare hemoglobin levels obtained using a transcutaneous spectroscopic device (Mediscan 2000, MBR Optical Systems, Wuppertal, Germany) with venous or capillary blood samples in neonates. Methods: Single-center prospective cohort study of term and preterm infants. The white light spectroscopic device was placed on the forearm for 60 s to measure hemoglobin content within 4 h of venous or capillary blood sampling. Pain reactions of the infants were assessed by using a neonatal pain assessment tool. Results were analyzed by Bland-Altman comparison and Wilcoxon signed-rank test. Results: 80 infants (mean gestational age 29.8 ± 3.8 weeks, mean birth weight 1,300 ± 690 g) were enrolled into the study. A total of 313 spectroscopic recordings within 2 h of a clinically indicated blood sample (181 capillary, 142 venous) were taken. The correlation coefficient R2 was 0.96 for capillary/spectroscopic and 0.99 for venous/spectroscopic pairs. Pain scores were significantly less for the spectroscopic measurements (p < 0.01). Conclusion: The results show good correlation between the hemoglobin blood levels and spectroscopic measurements. The slightly lower correlation coefficient for the capillary samples demonstrates a naturally higher variance in these values due to the laboratory method.
Very Late (10-Year-Old) Bare Metal Stent Thrombosis
Authors: Shaw Eric Scot , Singh Vikas , Martinezclark Pedro , O’Neill William W.
Published: November 2009

We present findings from a 59-year-old male patient who presented with coronary artery disease and refractory angina. Ten years prior, the patient had been implanted with 5 bare metal stents (BMS); he arrived with non-specific ST-T wave abnormalities. Angiographic data revealed a totally occluded right coronary artery at the level of the previously placed BMS, consistent with an acute occlusion and a significant thrombus. Our findings revealed that BMS thrombosis can occur as late as 10 years after implantation. Further data through clinical trials are warranted to look at this rare, but serious, complication.
Effect of Stannous Fluoride and Dilute Hydrofluoric Acid on Early Enamel Erosion over Time in vivo
Authors: Hjortsjö C. , Jonski G. , Thrane P.S. , Saxegaard E. , Young A.
Published: November 2009

Recent experimental in vivo studies have shown that aqueous solutions of stannous fluoride (SnF2) and hydrofluoric acid (HF) can reduce enamel solubility after 5 min. The aim of this study was to evaluate the longer-term protective effect of SnF2 (0.78%, pH 2.9) and HF (0.2%, pH 2.0) (both ∼0.1 mol/l F) using the same experimental model. Labial surfaces of healthy anterior teeth (all four surfaces when possible, otherwise a pair of surfaces) in 103 subjects (n = 399 teeth) were exposed to citric acid (0.01 mol/l, pH 2.7). The acid was applied using a peristaltic pump (5 ml, 6 ml/min) and was collected in coded test tubes (etch I). The test solutions were then applied to the same surfaces of the teeth (1 min, 6 ml/min). After either 1, 7, 14 or 28 days, citric acid was again applied to the same surfaces and subsequently collected (etch II). Enamel solubility was examined by assessment of calcium concentration in etch I and etch II solutions using atom absorption spectroscopy. Median values were calculated for all time periods and statistical analysis was carried out using the Wilcoxon signed-ranks test. Results showed that HF reduced enamel solubility by 54 and 36% after 1 and 7 days, respectively. After 14 and 28 days, there was no longer any effect. SnF2 showed no protective effect after the first day. Given these results, repeated application of HF and especially SnF2 may be necessary to improve the protective effect of these fluorides, and this requires further testing.
Treatment of Psoriasis with Anti-TNF Drugs during Pregnancy: Case Report and Review of the Literature
Authors: Puig Lluís , Barco Didac , Alomar Agustín
Published: November 2009

Published experiences of TNF-α inhibition during pregnancy consist of a limited number of case reports, series and ongoing registry data in patients with arthritis and inflammatory bowel disease. A 28-year-old woman – with psoriasis vulgaris since she was 8 years of age and generalized pustular psoriasis during her first pregnancy (partially controlled with ciclosporin, oral prednisone and topical corticosteroids, when lupus anticoagulant was detected at another hospital) – presented 4 months after delivery with severe psoriasis (PASI = 15.4) that did not respond to ciclosporin (3 mg/kg/day). Ten days after the first infusion of infliximab (5 mg/kg), when the patient became aware that she was pregnant again, there was PASI75 response, and the patient wished to continue this treatment after being fully informed. Complete blanching was achieved by week 6 of treatment, and was maintained thereafter until the moment of writing (19 months after the start of treatment). She gave birth by caesarean delivery to a healthy female baby, who was breastfed for 1 month and has developed normally. The current report extends the available evidence on successful infliximab treatment in pregnant women, with the first case of a patient with psoriasis who presented impetigo herpetiformis during her previous pregnancy. No detectable adverse effects were detected in the neonate, despite potential exposure to infliximab throughout gestation and breastfeeding. Even though absolute safety is difficult to prove, available data suggest that women who become pregnant while taking infliximab or other anti-TNFα agents can be reassured regarding the continuation of pregnancy.
Age-Related Changes in Neuromuscular Function and Performance following a High-Intensity Intermittent Task in Endurance-Trained Men
Authors: Bieuzen François , Hausswirth Christophe , Louis Julien , Brisswalter Jeanick
Published: November 2009

Background: Much attention has been focused on the need to design strategies to increase functional capacities in older populations. This has raised several questions regarding the ability of regular endurance training to preserve functional capacity with age. Objective: The purpose of this study was to examine the age-associated changes in neuromuscular function in endurance-trained men before and after a high-intensity, intermittent fatiguing task. Method: Twenty-six healthy endurance-trained male subjects: 16 older (59–79 years) and 10 young (20–34 years) men performed a high-intensity, intermittent fatiguing exercise corresponding to 10 sets of 10 repetitions on a horizontal leg press at 70% of the individual one-repetition maximum. Maximal voluntary contractions and evoked contractions of the knee extensor muscles were performed before and after the exercise. Results: Decreases in maximum voluntary contractions (older: –9.7%; young: –14.3%) and electromyographic activity were not different between groups. Peak twitch torque was reduced only for the older men and no changes in voluntary activation and M-wave properties were recorded in either group. Conclusion: The present study indicates that in endurance-trained men aged 59–79 years, muscle functional capacities are maintained despite losses in strength and contractile function related to the age.
A Dissociation of Attention and Awareness in Phase-sensitive but Not Phase-insensitive Visual Channels
Authors: Brascamp Jan W. , van Boxtel Jeroen J. A. , Knapen Tomas H. J. , Blake Randolph
Published: November 2009

The elements most vivid in our conscious awareness are the ones to which we direct our attention. Scientific study confirms the impression of a close bond between selective attention and visual awareness, yet the nature of this association remains elusive. Using visual afterimages as an index, we investigate neural processing of stimuli as they enter awareness and as they become the object of attention. We find evidence of response enhancement accompanying both attention and awareness, both in the phase-sensitive neural channels characteristic of early processing stages and in the phase-insensitive channels typical of higher cortical areas. The effects of attention and awareness on phase-insensitive responses are positively correlated, but in the same experiments, we observe no correlation between the effects on phase-sensitive responses. This indicates independent signatures of attention and awareness in early visual areas yet a convergence of their effects at more advanced processing stages.
Speech and Span: Working Memory Capacity Impacts the Use of Animacy but Not of World Knowledge during Spoken Sentence Comprehension
Authors: Nakano Hiroko , Saron Clifford , Swaab Tamara Y.
Published: November 2009

We present results from a study demonstrating that high- and low-span listeners show qualitatively different brain responses when comprehending simple active sentences. Participants listened to naturally produced sentences in three conditions in which the plausibility of thematic relations was manipulated, for instance: The dog(1)/The poet(2)/The box(3) is biting the mailman. Event-related potentials were recorded to the first noun, the verb, and the second noun in all three conditions. In (2), the thematic relations between the words in the sentence are less expected given our world knowledge, and this resulted in an N400 effect of semantic processing difficulty to the second noun for both high- and low-span subjects. In (3), the inanimate first noun cannot be the agent of the verb. Only high-span subjects showed an effect of animacy on the sentence-initial nouns, evident from a larger anterior negative shift to inanimate than animate nouns. Furthermore, to the thematically violated verbs (3), low-span subjects showed an N400, whereas high-span subjects generated a P600. We suggest that this P600 effect to the thematically violated verb may be related to processing costs resulting from a conflict between the provisional thematic roles assigned as a function of the inanimate sentence-initial noun, and the actual (animate) agent required by the verb. We further argue that low-span subjects lag behind those with high span in their use of animacy, but not real-world knowledge in the on-line computation of thematic roles in spoken language comprehension.
In the Eye of the Beholder: Internally Driven Uncertainty of Danger Recruits the Amygdala and Dorsomedial Prefrontal Cortex
Authors: Zaretsky Michal , Mendelsohn Avi , Mintz Matti , Hendler Talma
Published: November 2009

Interpretation of emotional context is a pivotal aspect of understanding social situations. A critical component of this process is assessment of danger levels in the surrounding, which may have a direct effect on the organism's survival. The limbic system has been implicated in mediating this assessment. In situations of uncertainty, the evaluation process may also call for greater involvement of prefrontal cortex for decision-making and planning of an appropriate behavioral response. In the following study, morphed face images depicting emotional expressions were used to examine brain correlates of subjective uncertainty and perceptual ambiguity regarding danger. Fear and neutral expressions of 20 faces were morphed, and each of the face videos was divided into three sequences of equal length representing three levels of objective certainty regarding the expressions neutral, fear, and ambiguous. Sixteen subjects were scanned in a 1.5-T scanner while viewing 60 × 6-sec video sequences and were asked to report their subjective certainty regarding the level of danger surrounding the face on a four-level scale combining definite/maybe and danger/no-danger values. The individual responses were recorded and used as the basis for a “subjective protocol” versus an “objective protocol.” Significant activations of the amygdala, dorsomedial prefrontal cortex, and dorsolateral prefrontal cortex were observed under the subjective protocol of internally driven uncertainty, but not under objective stimuli-based ambiguity. We suggest that this brain network is involved in generating subjective assessment of social affective cues. This study provides further support to the “relevance detector” theory of the amygdala and implicates its importance to behavior relying heavily on subjective assessment of danger, such as in the security domain context.
Refreshing and Integrating Visual Scenes in Scene-selective Cortex
Authors: Park Soojin , Chun Marvin M. , Johnson Marcia K.
Published: November 2009

Constructing a rich and coherent visual experience involves maintaining visual information that is not perceptually available in the current view. Recent studies suggest that briefly thinking about a stimulus (refreshing) can modulate activity in category-specific visual areas. Here, we tested the nature of such perceptually refreshed representations in the parahippocampal place area (PPA) and retrosplenial cortex (RSC) using fMRI. We asked whether a refreshed representation is specific to a restricted view of a scene, or more view-invariant. Participants saw a panoramic scene and were asked to think back to (refresh) a part of the scene after it disappeared. In some trials, the refresh cue appeared twice on the same side (e.g., refresh left–refresh left), and other trials, the refresh cue appeared on different sides (e.g., refresh left–refresh right). A control condition presented halves of the scene twice on same sides (e.g., perceive left–perceive left) or different sides (e.g., perceive left–perceive right). When scenes were physically repeated, both the PPA and RSC showed greater activation for the different-side repetition than the same-side repetition, suggesting view-specific representations. When participants refreshed scenes, the PPA showed view-specific activity just as in the physical repeat conditions, whereas RSC showed an equal amount of activation for different- and same-side conditions. This finding suggests that in RSC, refreshed representations were not restricted to a specific view of a scene, but extended beyond the target half into the entire scene. Thus, RSC activity associated with refreshing may provide a mechanism for integrating multiple views in the mind.
Action Preparation Helps and Hinders Perception of Action
Authors: Press Clare , Gherri Elena , Heyes Cecilia , Eimer Martin
Published: November 2009

Several theories of the mechanisms linking perception and action require that the links are bidirectional, but there is a lack of consensus on the effects that action has on perception. We investigated this by measuring visual event-related brain potentials to observed hand actions while participants prepared responses that were spatially compatible (e.g., both were on the left side of the body) or incompatible and action type compatible (e.g., both were finger taps) or incompatible, with observed actions. An early enhanced processing of spatially compatible stimuli was observed, which is likely due to spatial attention. This was followed by an attenuation of processing for both spatially and action type compatible stimuli, likely to be driven by efference copy signals that attenuate processing of predicted sensory consequences of actions. Attenuation was not response-modality specific; it was found for manual stimuli when participants prepared manual and vocal responses, in line with the hypothesis that action control is hierarchically organized. These results indicate that spatial attention and forward model prediction mechanisms have opposite, but temporally distinct, effects on perception. This hypothesis can explain the inconsistency of recent findings on action–perception links and thereby supports the view that sensorimotor links are bidirectional. Such effects of action on perception are likely to be crucial, not only for the control of our own actions but also in sociocultural interaction, allowing us to predict the reactions of others to our own actions.
A Critical Location of the Contemporary Black Church
Authors: Tillotson Michael
Published: November 2009

This article explores attempts to transform Black forms of Christianity to assess their effectiveness in relationship to advancing African agency and cultural values. Utilizing an Afrocentric perspective that insists on discovering location in phenomenal and intellectual texts as a way of indicating distance from reality and history, this work intends to examine the relevance of the Word Church formation in the African American community. This article does not ask whether one form of religion is superior to another but rather how a certain form of spirituality is congruent to historical realities. Taking the term Colonial Christianity to mean the specific religion transmitted to enslaved and free Africans in the United States of America between the l7th and 20th centuries, this article engages the permutations of that religion in the minds of Africans in order to examine psychological dislocation.
Theoretical and Experimental Study on Die Pressure Prediction in Extrusion of Wood-Plastic Composite
Authors: Behravesh A.H. , Shakouri E. , Zolfaghari A. , Golzar M.
Published: November 2009

This article presents a theoretical and experimental study on the measurement and prediction of die pressure in the extrusion process of wood-plastic composite (WPC). Die pressure is an important parameter in processing of WPCs as it governs the product strength, quality, and the final output rate, which directly affects the economy of the production. In this research work, a modular die was designed to accommodate for various circular die inserts to produce rod-shaped products having various diameters. Experimentation was carried out to record the pressure for each product. To develop a theoretical formulation for die pressure, two different schemes were considered and modified: non-Newtonian flow and hot extrusion. The comparison of the experimental and theoretical results demonstrated that the experimental values are between the values predicted by the two theoretical schemes. However, it was shown that by applying a correction factor (based on the compaction ratio of die) into the hot extrusion scheme, a theoretical ground can be suggested for pressure prediction in WPC processing. It appeared that the WPC flow in the die resembles more of a plug flow.
Modeling Steady State Creep in Functionally Graded Thick Cylinder Subjected to Internal Pressure
Authors: Singh Tejeet , Gupta V.K.
Published: November 2009

The steady state creep behavior in an isotropic functionally graded composite cylinder, subjected to internal pressure has been investigated. The cylinder is assumed to be made of composite containing silicon carbide particles in a matrix of pure aluminum. The creep behavior of the material has been described by threshold stress based creep law with a stress exponent of five. The effect of imposing linear particle gradient on the distribution of stress and strain rates in the composite cylinder has been investigated. The study reveals that for the assumed linear particle distribution, the radial stress decreases throughout the cylinder with increase in particle gradient, whereas the tangential, axial, and effective stresses increase significantly near the inner radius but show significant decrease toward the outer radius. The strain rates in the composite cylinder could be reduced significantly by employing gradient in the distribution of reinforcement while keeping the same average amount of reinforcement.
Modal Verb Usage at the Interface of English and a Related Creole: A Corpus-based Study of Can/Could and Will/Would in Trinidadian English
Authors: Deuber Dagmar
Published: November 2009

In Trinidad, English coexists with an English-based Creole in a Creole continuum. Creole could is equivalent to international Standard English can, and would to will. Previous authors have observed that the Creole exerts a strong influence on the use of these modals in Trinidadian English. This article presents a detailed analysis, based on data from the International Corpus of English, of the use of can/could and will/would in this variety. Comparisons are drawn with other varieties, especially British English. Quantitative distributions as well as uses and meanings of the modals are analyzed. It is shown that distinctions between the members of each pair of modals are not lost generally but are liable to be blurred in particular categories of uses where they are relatively weak anyway, consisting only in the degree of tentativeness or politeness implied, for example. Furthermore, the data indicate that the use of will in present habitual contexts is more prominent in Trinidadian than in British English, probably as a result of influence from the Creole marker of present habitual aspect; would is commonly used in present habitual contexts as well.
Social Aggression and Social Position in Middle Childhood and Early Adolescence: Burning Bridges or Building Them?
Authors: Watling Neal Jennifer
Published: November 2009

Because the mechanism of harm used in social aggression generally involves the manipulation of peer relationships, it is important to consider its social correlates. The current article uses social dominance theory as a frame to review developmental research on social aggression perpetration and three indicators of social position: sociometric status, perceived popularity, and social network position. Consistent with social dominance theory, social aggression is positively associated with indicators of social position that reflect influence in the peer hierarchy (i.e., perceived popularity and social network position). However, these behaviors are also negatively associated with indicators of social position that reflect likeability (i.e., sociometric status), suggesting that they are not without social trade-offs. Thus, depending on how social position is operationalized, social aggression can be associated with building or burning bridges to peers. Potential moderators and implications for intervention within school-based contexts are discussed.