bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetic and endocrine emergencies
Authors: Kearney T , Dang C 
Published: February 2007

Abstract
Endocrine emergencies constitute only a small percentage of the emergency workload of general doctors, comprising about 1.5% of all hospital admission in England in 2004–5. Most of these are diabetes related with the remaining conditions totalling a few hundred cases at most. Hence any individual doctor might not have sufficient exposure to be confident in their management. This review discusses the management of diabetic ketoacidosis, hyperosmolar hyperglycaemic state, hypoglycaemia, hypercalcaemia, thyroid storm, myxoedema coma, acute adrenal insufficiency, phaeochromocytoma hypertensive crisis and pituitary apoplexy in the adult population.
Is rheumatoid arthritis a disease that starts in the intestine? A pilot study comparing an elemental diet with oral prednisolone
Authors: Podas Thrasyvoulos , Nightingale Jeremy M D , Oldham Roger , Roy S , Sheehan Nicholas J , Mayberry John F 
Published: February 2007

Abstract

Objectives
This pilot study aimed to determine if an elemental diet could be used to treat patients with active rheumatoid arthritis and to compare its effect to that of oral prednisolone.

Methods
Thirty patients with active rheumatoid arthritis were randomly allocated to 2 weeks of treatment with an elemental diet (n = 21) or oral prednisolone 15 mg/day (n = 9). Assessments of duration of early morning stiffness (EMS), pain on a 10 cm visual analog scale (VAS), the Ritchie articular index (RAI), swollen joint score, the Stanford Health Assessment Questionnaire, global patient and physician assessment, body weight, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and haemoglobin, were made at 0, 2, 4 and 6 weeks.

Results
All clinical parameters improved in both groups (p&lt;0.05) except the swollen joint score in the elemental diet group. An improvement of greater than 20% in EMS, VAS and RAI occurred in 72% of the elemental diet group and 78% of the prednisolone group. ESR, CRP and haemoglobin improved in the steroid group only (p&lt;0.05).

Conclusions
An elemental diet for 2 weeks resulted in a clinical improvement in patients with active rheumatoid arthritis, and was as effective as a course of oral prednisolone 15 mg daily in improving subjective clinical parameters. This study supports the concept that rheumatoid arthritis may be a reaction to a food antigen(s) and that the disease process starts within the intestine.
An audit of “do not attempt resuscitation” decisions in two district general hospitals: do current guidelines need changing?
Authors: Harris Dylan , Davies Rachel 
Published: February 2007

Abstract

Introduction
Doctors in all specialties are involved in making “do not attempt resuscitation” (DNAR) decisions; this can be a difficult and challenging process. Guidelines exist to provide an ethical and legal framework for the process and documentation of these decisions.

Objective
To audit the documentation of resuscitation decisions in a sample of medical inpatients from two district general hospitals.

Method
A retrospective case note audit of 50 medical inpatients, in which a DNAR decision had been made (28 from hospital 1, 22 from hospital 2).

Results
Average age was 78.9 years (48% male:52% female). In both hospitals DNAR decisions were usually discussed with relatives (84%), documented in nursing notes (100%) and made by senior team members (90%). Although the decision was usually dated and clearly documented (98%), abbreviations were commonly used in hospital 2 (45.5% vs 0% in hospital 1, p&lt;0.05). Decisions regarding other treatment were not consistently documented (78.6% and 72.7%, respectively) and there was little evidence that decisions were reviewed (14.3% and 31.8%). The decision was rarely discussed with the patient (6% of all patients), although 66% of patients were not in a position to have a discussion.

Conclusions
Specific forms for recording DNAR decisions improve the clarity of documentation. Current recommendations to discuss resuscitation with patients are controversial and not followed. However, many patients are not in a position to hold a discussion when the need arises and the guidelines should advocate early discussion during a hospital admission in patients where this is appropriate, prior discussion with family and/or wider use of advanced directives.
PARALLEL DELAUNAY REFINEMENT: ALGORITHMS AND ANALYSES
Authors: SPIELMAN DANIEL A. , TENG SHANG-HUA , ÜNGÖR ALPER 
Published: February 2007

We present a parallel Delaunay refinement algorithm for generating well-shaped meshes in both two and three dimensions. Like its sequential counterparts, the parallel algorithm iteratively improves the quality of a mesh by inserting new points, the Steiner points, into the input domain while maintaining the Delaunay triangulation. The Steiner points are carefully chosen from a set of candidates that includes the circumcenters of poorly-shaped triangular elements. We introduce a notion of independence among possible Steiner points that can be inserted simultaneously during Delaunay refinements and show that such a set of independent points can be constructed efficiently and that the number of parallel iterations is O( log 2Δ), where Δ is the spread of the input — the ratio of the longest to the shortest pairwise distances among input features. In addition, we show that the parallel insertion of these set of points can be realized by sequential Delaunay refinement algorithms such as by Ruppert's algorithm in two dimensions and Shewchuk's algorithm in three dimensions. Therefore, our parallel Delaunay refinement algorithm provides the same shape quality and mesh-size guarantees as these sequential algorithms. For generating quasi-uniform meshes, such as those produced by Chew's algorithms, the number of parallel iterations is in fact O( log Δ). To the best of our knowledge, our algorithm is the first provably polylog(Δ) time parallel Delaunay-refinement algorithm that generates well-shaped meshes of size within a constant factor of the best possible.
Tumor-Suppressive Effects of Pannexin 1 in C6 Glioma Cells
Authors: Lai Charles P.K. , Bechberger John F. , Thompson Roger J. , MacVicar Brian A. , Bruzzone Roberto , Naus Christian C. 
Published: February 2007

Abstract
Mammalian gap junction proteins, connexins, have long been implicated in tumor suppression. Recently, a novel family of proteins named pannexins has been identified as the mammalian counterpart of the invertebrate gap junction proteins, innexins. To date, pannexin 1 (Panx1) and pannexin 2 (Panx2) mRNAs are reported to be expressed in the brain. Most neoplastic cells, including rat C6 gliomas, exhibit reduced connexin expression, aberrant gap junctional intercellular communication (GJIC), and an increased proliferation rate. When gap junctions are up-regulated by transfecting C6 cells with connexin43, GJIC is restored and the proliferation is reduced. In this study, we examined the tumor-suppressive effects of Panx1 expression in C6 cells. Reverse transcription-PCR analysis revealed that C6 cells do not express any of the pannexin transcripts, whereas its nontumorigenic counterpart, rat primary astrocytes, exhibited mRNAs for all three pannexins. On generation of stable C6 transfectants with tagged Panx1 [myc or enhanced green fluorescent protein (EGFP)], a localization of Panx1 expression to the Golgi apparatus and plasma membrane was observed. In addition, Panx1 transfectants exhibited a flattened morphology, which differs greatly from the spindle-shaped control cells (EGFP only). Moreover, Panx1 expression increased gap junctional coupling as shown by the passage of sulforhodamine 101. Finally, we showed that stable expression of Panx1 in C6 cells significantly reduced cell proliferation in monolayers, cell motility, anchorage-independent growth, and in vivo tumor growth in athymic nude mice. Altogether, we conclude that the loss of pannexin expression may participate in the development of C6 gliomas, whereas restoration of Panx1 plays a tumor-suppressive role. [Cancer Res 2007;67(4):1545–54]
Specific Targeting of Tumor Angiogenesis by RGD-Conjugated Ultrasmall Superparamagnetic Iron Oxide Particles Using a Clinical 1.5-T Magnetic Resonance Scanner
Authors: Zhang Chunfu , Jugold Manfred , Woenne Eva C. , Lammers Twan , Morgenstern Bernd , Mueller Margareta M. , Zentgraf Hanswalter , Bock Michael , Eisenhut Michael , Semmler Wolfhard , Kiessling Fabian 
Published: February 2007

Abstract
Angiogenesis is essential for the development of malignant tumors and provides important targets for tumor diagnosis and therapy. To noninvasively assess the angiogenic profile of tumors, novel αvβ3 integrin–targeted ultrasmall superparamagnetic iron oxide particles (USPIOs) were designed and their specific uptake by endothelial cells was evaluated in vitro and in vivo. USPIOs were coated with 3-aminopropyltrimethoxysilane (APTMS) and conjugated with Arg-Gly-Asp (RGD) peptides. Accumulation in human umbilical vein endothelial cells (HUVECs) was evaluated using Prussian blue staining, transmission electron microscopy, magnetic resonance (MR) imaging, and inductively coupled plasma mass spectrometry. Uptake of RGD-USPIO by HUVECs was significantly increased when compared with unlabeled USPIO and could be competitively inhibited by addition of unbound RGD. The ability of the RGD-USPIO to noninvasively distinguish tumors with high (HaCaT-ras-A-5RT3) and lower (A431) area fractions of αvβ3 integrin–positive vessels was evaluated using a 1.5-T MR scanner. Indeed, after RGD-USPIO injection, there was a more pronounced decrease in T2 relaxation times in HaCaT-ras-A-5RT3 tumors than in A431 tumors. Furthermore, T2*-weighted images clearly identified the heterogeneous arrangement of vessels with αvβ3 integrins in HaCaT-ras-A-5RT3 tumors by an irregular signal intensity decrease. In contrast, in A431 tumors with predominantly small and uniformly distributed vessels, the signal intensity decreased more homogeneously. In summary, RGD-coupled, APTMS-coated USPIOs efficiently label αvβ3 integrins expressed on endothelial cells. Furthermore, these molecular MR imaging probes are capable of distinguishing tumors differing in the degree of αvβ3 integrin expression and in their angiogenesis profile even when using a clinical 1.5-T MR scanner. [Cancer Res 2007;67(4):1555–62]
Sp1 Is Required for Transforming Growth Factor-β–Induced Mesenchymal Transition and Migration in Pancreatic Cancer Cells
Authors: Jungert Kerstin , Buck Anita , Wichert Götz von , Adler Guido , König Alexander , Buchholz Malte , Gress Thomas M. , Ellenrieder Volker 
Published: February 2007

Abstract
Transition from a sessile epithelial phenotype to a migrating mesenchymal phenotype is a crucial step in transforming growth factor-β (TGF-β)–induced pancreatic cancer cell migration and invasion. These profound morphologic and functional alterations are associated with characteristic changes in TGF-β–regulated gene expression, defined by rapid repression of epithelial markers and a strong and sustained transcriptional induction of mesenchymal markers such as the intermediate filament vimentin. In this study, we have analyzed the role of the transcription factor Sp1 in TGF-β–induced and Smad-mediated gene regulation during epithelial to mesenchymal transition (EMT) and migration of pancreatic cancer cells. Here, we show that Sp1 is required for TGF-β–induced EMT, and that this function is especially mediated through transcriptional induction of vimentin. Our results emphasize the functional relevance of vimentin in TGF-β–induced EMT because prevention of its induction strongly reduces cell migration. Altogether, this study helps to better understand the role of Sp1 in TGF-β–induced progression of pancreatic cancer. It suggests that Sp1, via transcriptional induction of vimentin, cooperates with activated Smad complexes in mesenchymal transition and migration of pancreatic cancer cells upon TGF-β stimulation. [Cancer Res 2007;67(4):1563–70]
Toll-like Receptor-7 Tolerizes Malignant B Cells and Enhances Killing by Cytotoxic Agents
Authors: Shi Yonghong , White Dionne , He Liwei , Miller Richard L. , Spaner David E. 
Published: February 2007

Abstract
Chronic activation through Toll-like receptors (TLR) occurs in a number of pathologic settings, but has not been studied to the same extent as primary activation. TLR7, expressed by B cells and some dendritic cells, recognizes molecular patterns associated with viruses that can be mimicked by synthetic imidazoquinolines. In response to primary stimulation with the imidazoquinoline, S28690, human mononuclear cells produced tumor necrosis factor-α, but were unable to do so upon restimulation with S28690. This state of “tolerization” lasted at least 5 days. Using chronic lymphocytic leukemia B cells as a model to facilitate biochemical analysis, the tolerized state was found to be associated with altered receptor components, including down-regulated expression of TLR7 mRNA and decreased levels of interleukin-1 receptor-associated kinase 1. Tolerization was characterized by a transcriptionally regulated block in stress-activated protein kinase and nuclear factor κB activation, with relatively preserved activation of extracellular signal-regulated kinase (ERK). Tolerized chronic lymphocytic leukemia cells were found to be more sensitive to cytotoxic chemotherapeutic agents, in part through altered stress-activated protein kinase signaling pathways. This property of the TLR7-tolerized state may potentially be exploited in the treatment of B cell cancers. [Cancer Res 2007;67(4):1823–31
Imaging-Guided Gene Therapy of Experimental Gliomas
Authors: Jacobs Andreas H. , Rueger Maria Adele , Winkeler Alexandra , Li Hongfeng , Vollmar Stefan , Waerzeggers Yannic , Rueckriem Benedikt , Kummer Christiane , Dittmar Claus , Klein Markus , Heneka Michael T. , Herrlinger Ulrich , Fraefel Cornel , Graf Rudolf , Wienhard Klaus , Heiss Wolf-Dieter 
Published: February 2007

AbstractTo further develop gene therapy for patients with glioblastomas, an experimental gene therapy protocol was established comprising a series of imaging parameters for (i) noninvasive assessment of viable target tissue followed by (ii) targeted application of herpes simplex virus type 1 (HSV-1) amplicon vectors and (iii) quantification of treatment effects by imaging. We show that viable target tissue amenable for application of gene therapy vectors can be identified by multitracer positron emission tomography (PET) using 2-18F-fluoro-2-deoxy-d-glucose, methyl-11C-l-methionine, or 3′-deoxy-3′-18F-fluoro-l-thymidine ([18F]FLT). Targeted application of HSV-1 amplicon vectors containing two therapeutic genes with synergistic antitumor activity (Escherichia coli cytosine deaminase, cd, and mutated HSV-1 thymidine kinase, tk39, fused to green fluorescent protein gene, gfp) leads to an overall response rate of 68%, with 18% complete responses and 50% partial responses. Most importantly, we show that the “tissue dose” of HSV-1 amplicon vector–mediated gene expression can be noninvasively assessed by 9-[4-18F-fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG) PET. Therapeutic effects could be monitored by PET with significant differences in [18F]FLT accumulation in all positive control tumors and 72% in vivo transduced tumors (P = 0.01) as early as 4 days after prodrug therapy. For all stably and in vivo transduced tumors, cdIREStk39gfp gene expression as measured by [18F]FHBG-PET correlated with therapeutic efficiency as measured by [18F]FLT-PET. These data indicate that imaging-guided vector application with determination of tissue dose of vector-mediated gene expression and correlation to induced therapeutic effect using multimodal imaging is feasible. This strategy will help in the development of safe and efficient gene therapy protocols for clinical application. [Cancer Res 2007;67(4):1706–15]
Tumor-Suppressive Effect of Retinoid Receptor–Induced Gene-1 (RRIG1) in Esophageal Cancer
Authors: Huang Jie , Liang Zheng D. , Wu Tsung-Teh , Hoque Ashraful , Chen Hongli , Jiang Yan , Zhang Hongfu , Xu Xiao-chun 
Published: February 2007

Abstract
We previously showed that induction of retinoid receptor–induced gene-1 (RRIG1) expression inhibited RhoA activation and tumor cell colony formation, invasion, and proliferation, and these effects are associated with the suppression of extracellular signal-regulated protein kinases 1 and 2 phosphorylation and cyclooxygenase-2 expression. To further elucidate its role in tumor cell growth, gene expression, and tumorigenesis, we determined RRIG1 expression in breast and esophageal tissue specimens and then stably transfected RRIG1 into a TE-8 esophageal squamous cell carcinoma (SCC) cell line. We found that RRIG1 was expressed in normal mammary glands (10 of 10) but not all ductal carcinoma in situ [11 of 19 (57.9%), P = 0.018] and invasive cancer [14 of 30 (46.7%), P = 0.0023] tissues. Similarly, RRIG1 was expressed in normal esophageal epithelium (22 of 22) but not all dysplastic [6 of 43 (14%), P = 0.0001] and SCC [50 of 122 (41%), P = 0.0001] tissues. Furthermore, RRIG1 expression correlated positively with tumor differentiation but inversely with lymph node metastasis of esophageal SCC. Finally, the stable transfection of RRIG1 inhibited esophageal SCC cell growth and the expression of extracellular signal-regulated protein kinases 1 and 2 and cell cycle–related genes (e.g., cyclin D1, phosphorylated Rb, and E2F). RRIG1-transfected sublines also inhibited tumor development in nude mice. The results of this study indicate that RRIG1 plays a role in suppressing tumorigenesis. [Cancer Res 2007;67(4):1589–93]
Activation of TLX3 and NKX2-5 in t(5;14)(q35;q32) T-Cell Acute Lymphoblastic Leukemia by Remote 3′-BCL11B Enhancers and Coregulation by PU.1 and HMGA1
Authors: Nagel Stefan , Scherr Michaela , Kel Alexander , Hornischer Klaus , Crawford Gregory E. , Kaufmann Maren , Meyer Corinna , Drexler Hans G. , MacLeod Roderick A.F. 
Published: February 2007

Abstract
In T-cell acute lymphoblastic leukemia, alternative t(5;14)(q35;q32.2) forms effect dysregulation of either TLX3 or NKX2-5 homeobox genes at 5q35 by juxtaposition with 14q32.2 breakpoints dispersed across the BCL11B downstream genomic desert. Leukemic gene dysregulation by t(5;14) was investigated by DNA inhibitory treatments with 26-mer double-stranded DNA oligonucleotides directed against candidate enhancers at, or near, orphan T-cell DNase I hypersensitive sites located between 3′-BCL11B and VRK1. NKX2-5 down-regulation in t(5;14) PEER cells was almost entirely restricted to DNA inhibitory treatment targeting enhancers within the distal breakpoint cluster region and was dose and sequence dependent, whereas enhancers near 3′-BCL11B regulated that gene only. Chromatin immunoprecipitation assays showed that the four most effectual NKX2-5 ectopic enhancers were hyperacetylated. These enhancers clustered ∼1 Mbp downstream of BCL11B, within a region displaying multiple regulatory stigmata, including a TCRA enhancer motif, deep sequence conservation, and tight nuclear matrix attachment relaxed by trichostatin A treatment. Intriguingly, although TLX3/NKX2-5 promoter/exon 1 regions were hypoacetylated, their expression was trichostatin A sensitive, implying extrinsic regulation by factor(s) under acetylation control. Knockdown of PU.1, known to be trichostatin A responsive and which potentially binds TLX3/NKX2-5 promoters, effected down-regulation of both homeobox genes. Moreover, genomic analysis showed preferential enrichment near ectopic enhancers of binding sites for the PU.1 cofactor HMGA1, the knockdown of which also inhibited NKX2-5. We suggest that HMGA1 and PU.1 coregulate ectopic homeobox gene expression in t(5;14) T-cell acute lymphoblastic leukemia by interactions mediated at the nuclear matrix. Our data document homeobox gene dysregulation by a novel regulatory region at 3′-BCL11B responsive to histone deacetylase inhibition and highlight a novel class of potential therapeutic target amid noncoding DNA. [Cancer Res 2007;67(4):1461–71]
NGEP, a Prostate-Specific Plasma Membrane Protein that Promotes the Association of LNCaP Cells
Authors: Das Sudipto , Hahn Yoonsoo , Nagata Satoshi , Willingham Mark C. , Bera Tapan K. , Lee Byungkook , Pastan Ira 
Published: February 2007

Abstract
NGEP is a prostate-specific gene identified by analysis of expressed sequence tag databases. RNA analysis revealed two spliced forms of NGEP mRNA: a short form encoding a soluble protein (NGEP-S) and a long form encoding a polytopic membrane protein (NGEP-L). Transient expression of myc epitope–tagged NGEP-L showed that it was localized to the plasma membrane. We have now produced a specific antibody to the COOH terminus of NGEP-L and showed that it detects an ∼100-kDa protein in extracts of normal prostate and prostate cancers that contain high levels of NGEP mRNA. The antibody detects a protein that is highly expressed on the apical and the lateral surfaces of normal prostate and prostate cancer cells by immunohistochemistry. The antibody does not detect a protein in the prostate cancer cell line LNCaP, which has very low NGEP mRNA levels. To study NGEP function, two stable LNCaP cell lines were prepared by transfection with NGEP-L and shown to contain similar amounts of NGEP-L protein as human prostate. Confocal immunofluorescence showed that NGEP-L is present on the plasma membrane of the transfected LNCaP cells and is highly concentrated at cell:cell contact regions. Furthermore, as the cell density increased, the cells formed large aggregates. A specific RNA interference that lowered NGEP-L levels prevented formation of cell aggregates. Our results suggest that NGEP-L has a role in promoting cell contact–dependent interactions of LNCaP prostate cancer cells and also that NGEP is a promising immunotherapy target for prostate cancer. [Cancer Res 2007;67(4):1594–601]
The Triterpenoid 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic Acid and Its Derivatives Elicit Human Lymphoid Cell Apoptosis through a Novel Pathway Involving the Unregulated Mitochondrial Permeability Transition Pore
Authors: Brookes Paul S. , Morse Kimberly , Ray Denise , Tompkins Andrew , Young Sara M. , Hilchey Shannon , Salim Suhail , Konopleva Marina , Andreeff Michael , Phipps Richard , Bernstein Steven H. 
Published: February 2007

Abstract
2-Cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its C28 imidazole and dinitrile derivatives are novel oleanane triterpenoids exhibiting promise as both therapeutic and preventative agents for cancer. Herein we show that these triterpenoids induce normal and malignant B-lymphoid cell apoptosis, with the C28 derivatives being more potent than CDDO, through a novel mitochondrial mechanism. We show using both normal and malignant human B cells, as well as isolated rat mitochondria, that CDDO directly interacts with a limited number of as yet undefined mitochondrial proteins. Such an interaction results in the loss of mitochondrial thiol status and the secondary modification of numerous mitochondrial protein thiols. Our data further suggest that such modifications result in the formation of high molecular weight protein aggregates that form “unregulated,” constitutively open, cyclosporin A–insensitive permeability transition (PT) pores. The formation of such PT pores results in the subsequent generation of mitochondrial superoxide and cell death. In total, our studies (a) suggest a novel mechanism of action for triterpenoid-induced cell death; (b) are among the first to directly support the existence of an unregulated PT pore formed by mitochondrial protein aggregates, as first proposed by Lemasters and colleagues; and (c) validate such an unregulated PT pore as a viable target for the development of new cancer therapeutics. [Cancer Res 2007;67(4):1793–802]