bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidermolytic hyperkeratosis with polycyclic posoriasiform plaques resulting from a mutation in the keratin 1 gene
Authors: Michael E. J. , Schneiderman P. , Grossman M. E. , Christiano A. M. 
Published: May 2007

AbstractEpidermolytic hyperkeratosis (EHK) is a genodermatosis caused by mutations in either the keratin 1 (K1) or keratin 10 (K10) genes, and characterized by erythroderma and blistering at birth, with development of a ribbed, ichthyotic hyperkeratosis and palmoplantar keratoderma. A wide variety of mutations within the highly conserved helix termination motifs of the central rod domains of the K1 or K10 genes correlate with the highly variable phenotypic severity observed in EHK. We report a unique EHK‐like phenotype exhibiting autosomal dominant inheritance with variable expressivity in four affected individuals in a single family. Clinically, affected individuals manifest transient blistering at birth followed by chronic diffuse palmoplantar keratoderma without transgradiens. Intermittent flares of non‐migratory polycylic erythematous psoriasiform plaques which worsen and abate in severity were present in all affected individuals, but showed immense individual variation in both severity and duration, ranging from weeks to months. Histopathologic examination of the psoriasiform plaques demonstrated the characteristic features of EHK. Sequencing of the K1 gene in affected family members revealed a heterozygous A‐to‐T transversion at nucleotide 1435 within exon 7, converting isoleucine (ATT) to phenylalanine (TTT), (I479F). The mutation resides within the highly conserved helix termination motif of the helix 2B segment of the K1 gene. This unique clinical phenotype and the associated K1 mutation have not been previously described, and the associated K1 mutation have not been previously described, and it is referred to here as EHK with polycyclic, psoriasiform plaques (EHK/PPP).
Basal cell carcinoma – an in‐vivo model of human tumour microcirculation?
Authors: Bedlow A. J. , Stanton A. W. B. , Cliff S. , Mortimer P. S. 
Published: May 2007

AbstractThe role of angiogenesis in tumour growth and metastasis is well established. However, investigation off tumour microcirculation to date have used either biopsy material from human tumours, or animal models in vivo. we have studied the tumour microcirculation in vivo in human skin cancers using video‐microscopy to examine 12 basal cell carcinomas (BCCs) on the head andneck of 11 patients, and compared the vessels with those seen in the peri‐lesional skin, and in normal control skin on the oppsite side of the body. The vessels seen within the BCCs were markedly abnormal qualitiatively, forming bizarre, disorganized patterns. Quantitative analysis revealed that the mean diameter (+standard deviation) of the largest vessel was significantly greater within the BCC (0.086+0.029 mm) than that in the control skin (0.034+0.012 mm) (P<0.001). The area fraction, a measure of the area a tissue occupied by vessels, was increased highly significantly within the BCCs (0.158+0.038) compared with both peri‐lesional skin (0.029+0.012) and control skin (0.027+0.010) (P0.001). Length density, the length of blood vessel per unit area of tissue, was also highly significantly greater within the lesion (210.22+66.05 cm−1) compared to peri‐lesional (27.10+ 15.67 cm−1) and control skin (28.27+15.81 cm−1) (P<0.001). This is the first study to have demonstrated that BCCs possess a distinct tumour microcirculation which can be observed directly, and assessed quantitatively. Prospective studies of tumour progression, possibly after intervention with angiogenesis inhibitors, are possible
Cytokine modulation of type XV collagen gene expression in human dermal fibroblast cultures
Authors: Kivirikko S. , Mauviel A. , Pihlajaniemi T. , Uitto J. 
Published: May 2007

AbstractThe expression of type XV collagen was studied in cultured human dermal fibroblasts exposed to transforming growth factor‐β (TGF‐β), tumor necrosis factor‐α (TNF‐α) or interleukin‐1β (IL‐1β), cytokines which have been shown previously to alter the expression of several extracellular matrix genes. TGF‐β enhanced the expression of the type XV collagen gene (COL15A1) in a time‐dependent manner, up to 4.3‐fold after 24 h of incubation, whereas TNF‐α and IL‐1β reduced the mRNA steady‐state levels by 32 and 80%, respectively. When TGF‐β and TNF‐α were added together to the cultures, the stimulatory effect of TGF‐β on type XV collagen gene expression was abrogated, indicating antagonistic modulation by these 2 cytokines. These data suggest that the cytokines tested in this study may contribute to the regulation of type XV collagen synthesis in a variety of tissues which have recently been shown to express this particular collagen gene.
Adverse events associated with intravenous iron infusion (low‐molecular‐weight iron dextran and iron sucrose): a systematic review
Authors: CRITCHLEY JULIA , DUNDAR YENAL 
Published: May 2007

SUMMARYIntravenous iron administration is an effective method of treating iron deficiency anemia, but there have been concerns about adverse side effects, particularly serious events such as anaphylactic reaction. Several different forms of intravenous iron are available, but few studies have attempted to compare the frequency of adverse events.We carried out a systematic review to assess the frequency of adverse drug events (ADEs) associated with (i) low‐molecular‐weight intravenous iron dextran and (ii) iron sucrose. We searched several electronic databases; two reviewers screened all studies identified and extracted data. We included 60 studies, but few directly compared adverse events associated with two or more forms of iron, and most were not specifically designed to evaluate adverse events.In general, with the exception of high‐molecular‐weight iron dextran (HMWID), serious or life‐threatening adverse events appeared rare. Several studies showed lower risks of ADEs on low‐molecular‐weight iron dextran (LMWID) compared with HMWID, and one large review found a reduced risk on LMWID compared with iron gluconate. Two studies showed little difference between iron sucrose and iron gluconate, and two further studies had similar rates of adverse drug events between iron sucrose and LMWID; however, the sample size for most of these studies was too small to draw firm conclusions. Adequately powered direct comparisons of different forms of intravenous iron are required to assess the safety profiles.
Intraoperative surgical considerations for enhanced recovery after elective colonic surgery
Authors: HENDRY PAUL , FEARON KENNETH C. H. 
Published: May 2007

SUMMARYCareful planning of the intraoperative stage of the surgical stay plays an important role in achieving progress through the perioperative component of a multimodal care pathway. This period will play a significant part of the patient’s hospital experience and may dictate the ability to achieve the postoperative targets of an enhanced recovery program. A review of the available evidence demonstrates where benefits can be made to contribute to the overall progress of the patient’s recovery. Elements considered include: wound siting and care, minimal access techniques, use of diathermy, insertion of drains and catheters, and aspects of surgical techniques. These areas, when combined as part of an ‘enhanced recovery after surgery’ program, should contribute to a more rapid patient recovery without any increase in complications.
Towards an Integrated Approach in Supporting Microbiological Food Safety Decisions
Authors: Havelaar A. H. , Bräunig J. , Christiansen K. , Cornu M. , Hald T. , Mangen M.‐J. J. , Mølbak K. , Pielaat A. , Snary E. , Van Pelt W. , Velthuis A. , Wahlström H. 
Published: May 2007

SummaryDecisions on food safety involve consideration of a wide range of concerns including the public health impact of foodborne illness, the economic importance of the agricultural sector and the food industry, and the effectiveness and efficiency of interventions. To support such decisions, we propose an integrated scientific approach combining veterinary and medical epidemiology, risk assessment for the farm‐to‐fork food chain as well as agricultural and health economy. Scientific advice is relevant in all stages of the policy cycle: to assess the magnitude of the food safety problem, to define the priorities for action, to establish the causes for the problem, to choose between different control options, to define targets along the food chain and to measure success.
Xeno-oestrogenic activity in serum as marker of occupational pesticide exposure
Authors: Andersen Helle Raun , Nielsen Flemming , Nielsen Jesper Bo , Kjaerstad Mia Birkhoej , Baelum Jesper , Grandjean Philippe 
Published: May 2007

Background:An increasing number of currently used pesticides are reported to possess oestrogen-like properties or to disturb the endocrine system in other ways.Objectives:To investigate if xeno-oestrogenic activity in serum can be used as a biomarker of the combined exposure to pesticides with oestrogen-like properties in an occupational setting.Methods:Serum samples were obtained from two separate cohorts representing non-pregnant and pregnant female greenhouse workers in Denmark. Serum samples from 270 non-pregnant women and 173 pregnant women were analysed for xeno-oestrogenic activity. A fraction containing major xeno-oestrogens but without pharmaceutical and endogenously produced oestrogens was isolated from each serum sample by solid-phase extraction and tested for oestrogenic response in a MCF-7 cell proliferation assay. The pesticide exposure for each woman was categorised as low, medium or high based on information collected by detailed interviews of the women and the employers.Results:In both cohorts, an exposure-associated increase in the xeno-oestrogenic activity in serum was demonstrated. Among the pregnant women, the association between pesticide exposure and xeno-oestrogenic activity in serum was statistically significant for women who had been at work within the last week, while no association was observed for women who had not been at work during the most recent week.Conclusions:The study illustrates the usefulness of this biomarker for qualitative assessment of the combined exposure to mixtures of oestrogen-like pesticides. Although the individual pesticides responsible for the xeno-oestrogenic response were not identified, the study demonstrates that, even within highly-controlled greenhouse operations, occupational exposure to oestrogen-like pesticides can result in detectable impacts on hormonal activity in the blood.
Limits of longitudinal decline for the interpretation of annual changes in FEV1in individuals
Authors: Hnizdo Eva , Sircar Kanta , Yan Tieliang , Harber Philip , Fleming James , Glindmeyer Henry W 
Published: May 2007

Objective:Spirometry-based screening programmes often conduct annual assessment of longitudinal changes in forced expiratory volume in 1 second (FEV1) to identify individuals with excessive rates of decline. Both the American Thoracic Society (ATS) and the American College of Occupational and Environmental Medicine (ACOEM) recommend a reference limit value of ⩾15% for excessive annual decline. Neither the ATS nor the ACOEM adjust this limit for the precision of the existing spirometry data. The authors propose an improved method of defining the reference limit of longitudinal annual FEV1decline (LLD) based on the precision of the spirometry data.Method:The authors used data from four monitoring programmes and measured their data precision using a pair-wise within-person variation statistic. They then derived programme- and gender-specific absolute and relative LLD values and validated these against the 95th percentiles for observed yearly changes in FEV1.Results:The relative limit for annual decline was more practical than the absolute limit as it adjusted for gender differences in the magnitude of FEV1. The programme-specific relative limit values were in good agreement with 95th percentiles for year-to-year FEV1changes and ranged from 6.6% to 15.8%. For individuals with COPD and bronchial hyperreactivity the 95th percentiles for year-to-year changes were about 15% and higher.Conclusions:The relative longitudinal limit for annual FEV1decline based upon precision of measurements is valid and can be generalised to different gender and population groups. A relative limit of approximately 10% appears appropriate for good quality workplace monitoring programmes, whereas a limit of about 15% appears appropriate for clinical evaluation of individuals with an obstructive airway disease. Computer software based on the method described is available from the corresponding author.
Effects of Oxide Thickness on Scale and Interface Stresses under Isothermal Cooling and Micro-Indentation for Ferritic Stainless Steel Interconnect
Authors: Sun Xin , Liu Wenning , Vetrano John , Yang Zhenguo Gary , Recknagle Kurtis P. , Khaleel Moe 
Published: May 2007

Interconnects in solid oxide fuel cells (SOFCs) provide the electrical connection between the individual cells, as well as separate the anode fuel from the cathode air for each cell. In this paper, we study the thermal stresses in the oxide scale and at the oxide/substrate interface for Cr-Fe based interconnect (IC), e.g. Crofer 22 APU, during cooling.	The ultimate goal is to predict the interconnect life under typical operating conditions and thermal cycles. In general, very high compressive in-plane stresses are predicted in the oxide layer during cooling. High shear stress is also predicted on the oxide scale/substrate interface. The predicted shear stress on the interface will be used to compare with the experimentally determined bond strength to predict delamination. Finite element analyses are also performed for indentation test: high shear stress is predicted on the oxide/substrate interface, and the interfacial crack growth is predicted to be mode II driven.
Inhibition of Angiogenesis and Tumor Metastasis by Targeting a Matrix Immobilized Cryptic Extracellular Matrix Epitope in Laminin
Authors: Akalu Abebe , Roth Jennifer M. , Caunt Maresa , Policarpio Desiree , Liebes Leonard , Brooks Peter C. 
Published: May 2007

AbstractAngiogenesis and tumor metastasis depend on extracellular matrix (ECM) remodeling and subsequent cellular interactions with these modified proteins. An in-depth understanding of how both endothelial and tumor cells use matrix-immobilized cryptic ECM epitopes to regulate invasive cell behavior may lead to the development of novel strategies for the treatment of human tumors. However, little is known concerning the existence and the functional significance of cryptic laminin epitopes in regulating angiogenesis and tumor cell metastasis. Here, we report the isolation and characterization of a synthetic peptide that binds to a cryptic epitope in laminin. The STQ peptide selectively bound denatured and proteolyzed laminin but showed little interaction with native laminin. The cryptic laminin epitope recognized by this peptide was selectively exposed within malignant melanoma in vivo, whereas little if any was detected in normal mouse skin. Moreover, the STQ peptide selectively inhibited endothelial and tumor cell adhesion, migration, and proliferation in vitro and inhibited angiogenesis, tumor growth, and experimental metastasis in vivo. This inhibitory activity was associated with a selective up-regulation of the cyclin-dependent kinase inhibitor P27KIP1 and induction of cellular senescence. These novel findings suggest the existence of functionally relevant cryptic laminin epitopes in vivo and that selective targeting of these laminin epitopes may represent an effective new strategy for the treatment of malignant tumors by affecting both the endothelial and tumor cell compartments. [Cancer Res 2007;67(9):4353–63]
The Hinge Region Regulates DNA Binding, Nuclear Translocation, and Transactivation of the Androgen Receptor
Authors: Haelens Annemie , Tanner Tamzin , Denayer Sarah , Callewaert Leen , Claessens Frank 
Published: May 2007

Abstract
The androgen receptor (AR) encoding gene can undergo mutations during the development and treatment of prostate cancer. Even in hormone-independent stages, mutations in the receptor paradoxically seem to result in an increased AR function. Two such point mutations have been described in the part of the AR involved in DNA binding and nuclear translocation, namely the hinge region. Despite a decreased nuclear translocation, these mutant ARs display increased transactivating potencies. Through detailed analysis of the hinge region, we found that deletion of residues 629 to 636 resulted in a stronger androgen response on different reporters, although this mutant displays an extremely low in vitro affinity for androgen response elements. This superactivity is independent of nuclear localization and can be inhibited by antiandrogens. Surprisingly, the AR activation functions, AF1 and AF2, are not dramatically affected when the inhibitory region (629-RKLKKLGN-636) is deleted, although cotransfected p160 coactivator TIF2 had a stronger potentiating effect in the absence of this motif. The ligand-dependent interaction between the amino-terminal domain and the ligand-binding domain (N/C interaction) plays an important role in transactivation by the AR. We found that this interaction is strongly enhanced by deletion of the inhibitory region. In conclusion, the description of prostate cancer mutations has led to the discovery of a complex role of the hinge region in nuclear localization, DNA binding, coactivator recruitment, and N/C interaction of the AR. [Cancer Res 2007;67(9):4514–23]
ErbB-2 Induces the Cyclin D1 Gene in Prostate Epithelial Cells In vitro and In vivo
Authors: Casimiro Mathew , Rodriguez Olga , Pootrakul Llana , Aventian Maral , Lushina Nadia , Cromelin Caroline , Ferzli Georgina , Johnson Kevin , Fricke Stanley , Diba Fantahun , Kallakury Bhaskar , Ohanyerenwa Chioma , Chen Maxine , Ostrowski Michael , Hung Mien-Chie , Rabbani Shafaat A. , Datar Ram , Cote Richard , Pestell Richard , Albanese Chris 
Published: May 2007

Abstract
The receptor tyrosine kinase ErbB-2 plays an important role in the regulation of growth factor–induced signal transduction cascades in the epithelium, and ErbB-2 is frequently overexpressed in epithelial tumors. Our previous studies on clinical prostate cancer specimens indicated that ErbB-2 expression was increased in patients undergoing hormone ablation therapy. We had also shown that the critical cell cycle regulatory gene cyclin D1 and its promoter were targets of proliferative signaling in prostate cancer cell lines, and that cyclin D1 was required for ErbB-2–induced mammary tumorigenesis. In the current studies, we found that increased ErbB-2 membrane expression correlated with increased nuclear cyclin D1 staining in clinical prostate cancer specimens, and that expression of ErbB-2 was capable of inducing cell cycle progression in human prostate cancer cell lines. We further showed that ErbB-2 induced the cyclin D1 promoter in DU145 cells, and that small interfering RNA knockdown of cyclin D1 protein levels blocked a significant proportion of the heregulin-induced cell cycle progression in LNCaP cells. Probasin promoter–targeted expression of an activated ErbB-2 isoform induced cyclin D1 expression in the mouse prostate, commensurate with prostate intraepithelial neoplasia. Together, these in vitro and in vivo studies identify cyclin D1 as a critical downstream target of ErbB-2 in the prostate epithelium, both of which are possible therapeutic targets for cancer intervention. Furthermore, our novel mouse model provides a useful platform for ongoing in vivo investigations of ErbB-2 signaling in the prostate epithelium. [Cancer Res 2007;67(9):4364–72]
Hypoxia and Hypoxia-Inducible Factor-1 Expression Enhance Osteolytic Bone Metastases of Breast Cancer
Authors: Hiraga Toru , Kizaka-Kondoh Shinae , Hirota Kiichi , Hiraoka Masahiro , Yoneda Toshiyuki 
Published: May 2007

Abstract
Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. The transcription factor hypoxia-inducible factor-1 (HIF-1) is a major regulator of adaptation to hypoxia and is implicated in the malignant progression of cancers. Here, we studied whether hypoxia and HIF-1 expression contribute to the development of bone metastases using a well-characterized animal model of bone metastasis in MDA-MB-231 human breast cancer cells. To study the role of hypoxia in bone metastases, we tested the effects of the fusion protein (TOP3), the oxygen-dependent degradation domain of HIF-1α fused with HIV-TAT, and procaspase-3. TOP3 selectively induced apoptosis in hypoxic tumor cells in vitro and significantly reduced bone metastases in vivo. We next examined the role of HIF-1 in bone metastases by establishing MDA-MB-231 cells overexpressing constitutively active or dominant-negative HIF-1α (MDA/CA-HIF or MDA/DN-HIF, respectively). Bone metastases of MDA/CA-HIF were significantly increased with elevated number of CD31-positive blood vessels. In contrast, bone metastases were significantly reduced in MDA/DN-HIF. Because the progression of osteolytic bone metastases is due in part to the imbalance between bone formation and bone resorption, we examined the effects of hypoxia and HIF-1 on the differentiation of osteoblasts and osteoclasts. Hypoxia and CA-HIF overexpression markedly inhibited osteoblastic differentiation, whereas hypoxia increased osteoclast-like cell formation. In conclusion, these results suggest that tumor-associated hypoxia and HIF-1 expression promote the progression of bone metastases in breast cancer. Our results also suggest that hypoxia and HIF-1 lead to the development of osteolytic bone metastases by suppressing osteoblast differentiation and promoting osteoclastogenesis. [Cancer Res 2007;67(9):4157–63]
Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231
Authors: Gallagher Shannon M. , Castorino John J. , Wang Dian , Philp Nancy J. 
Published: May 2007

Abstract
Metastatic cancer cells increase glucose consumption and metabolism via glycolysis, producing large quantities of lactate. Recent work has shown that lactate efflux is mediated by monocarboxylate transporters (MCT), which are composed of a catalytic unit (MCT) and an accessory subunit (CD147), comprising the functional lactate transporter. CD147, an extracellular matrix metalloproteinase (MMP) inducer, is highly expressed in metastatic cancer cells. Because aerobic glycolysis is a hallmark of metastatic cancer, we examined whether increases in CD147 expression were linked to MCT expression in MDA-MB-231, a highly metastatic breast cancer cell line. MCT4 mRNA and protein expression were increased in MDA-MB-231 cells compared with cells derived from normal mammary tissue. MCT4 colocalized with CD147 in the plasma membrane and in membrane blebs shed from the cell surface. Small interfering RNA–mediated silencing of MCT4 impaired the maturation and trafficking of CD147 to the cell surface, resulting in accumulation of CD147 in the endoplasmic reticulum. Silencing MCT4 also resulted in fewer membrane blebs and decreased migration of MDA-MB-231 cells in vitro. Knockdown of CD147 resulted in loss of MCT4 in the plasma membrane and accumulation of the transporter in endolysosomes. These studies establish for the first time that increased expression of CD147 in metastatic cancer cells is coupled to the up-regulation of MCT4. The synergistic activities of the MCT/CD147 complex could facilitate migration of tumor cells by CD147-mediated MMP induction and lactate-stimulated angiogenesis and hyaluronan production. These data provide a molecular link between two hallmarks of metastatic cancer: the glycolytic switch and increased expression of CD147. [Cancer Res 2007;67(9):4182–9]