bluuebunny/crossref_metadata_2025_split huggingface dataset:
How I treat essential thrombocythemia
Authors: Beer Philip A. , Erber Wendy N. , Campbell Peter J. , Green Anthony R. 
Published: November 2010

AbstractIn the past 5 years we have witnessed significant advances in both the diagnostic process and optimal therapy for patients with essential thrombocythemia (ET). Insights into the underlying molecular mechanisms have been accompanied by the development of new diagnostic tests and by an improved understanding of the relationship between ET and other related myeloproliferative neoplasms, such as polycythemia vera and primary myelofibrosis. In the first part of this review, we describe how recent molecular and histologic studies can be integrated into a streamlined diagnostic process that is applicable to everyday clinical practice. We also address areas of current diagnostic controversy, including heterogeneity within ET and the phenotypic overlap between ET, polycythemia vera, and primary myelofibrosis. In the second part, we provide an overview of our current approach to the treatment of ET, including risk stratification, choice of cytoreductive agent, and a consideration of special situations such as the pregnant or perioperative patient. Areas of controversy discussed include the identification of those at high risk of complications and therapeutic decisions in the younger patient.
Fibrinopeptides A and B release in the process of surface fibrin formation
Authors: Riedel Tomas , Suttnar Jiri , Brynda Eduard , Houska Milan , Medved Leonid , Dyr Jan E. 
Published: November 2010

AbstractFibrinogen adsorption on a surface results in the modification of its functional characteristics. Our previous studies revealed that fibrinogen adsorbs onto surfaces essentially in 2 different orientations depending on its concentration in the solution: “side-on” at low concentrations and “end-on” at high concentrations. In the present study, we analyzed the thrombin-mediated release of fibrinopeptides A and B (FpA and FpB) from fibrinogen adsorbed in these orientations, as well as from surface-bound fibrinogen-fibrin complexes prepared by converting fibrinogen adsorbed in either orientation into fibrin and subsequently adding fibrinogen. The release of fibrinopeptides from surface-adsorbed fibrinogen and from surface-bound fibrinogen-fibrin complexes differed significantly compared with that from fibrinogen in solution. The release of FpB occurred without the delay (lag phase) characteristic of its release from fibrinogen in solution. The amount of FpB released from end-on adsorbed fibrinogen and from adsorbed fibrinogen-fibrin complexes was much higher than that of FpA. FpB is known as a potent chemoattractant, so its preferential release suggests a physiological purpose in the attraction of cells to the site of injury. The N-terminal portions of fibrin β chains including residues Bβ15-42, which are exposed after cleavage of FpB, have been implicated in many processes, including angiogenesis and inflammation.
A microbial detection array (MDA) for viral and bacterial detection
Authors: Gardner Shea N , Jaing Crystal J , McLoughlin Kevin S , Slezak Tom R 
Published: November 2010

Abstract

Background
Identifying the bacteria and viruses present in a complex sample is useful in disease diagnostics, product safety, environmental characterization, and research. Array-based methods have proven utility to detect in a single assay at a reasonable cost any microbe from the thousands that have been sequenced.

Methods
We designed a pan-Microbial Detection Array (MDA) to detect all known viruses (including phages), bacteria and plasmids and developed a novel statistical analysis method to identify mixtures of organisms from complex samples hybridized to the array. The array has broader coverage of bacterial and viral targets and is based on more recent sequence data and more probes per target than other microbial detection/discovery arrays in the literature. Family-specific probes were selected for all sequenced viral and bacterial complete genomes, segments, and plasmids. Probes were designed to tolerate some sequence variation to enable detection of divergent species with homology to sequenced organisms, and to have no significant matches to the human genome sequence.

Results
In blinded testing on spiked samples with single or multiple viruses, the MDA was able to correctly identify species or strains. In clinical fecal, serum, and respiratory samples, the MDA was able to detect and characterize multiple viruses, phage, and bacteria in a sample to the family and species level, as confirmed by PCR.

Conclusions
The MDA can be used to identify the suite of viruses and bacteria present in complex samples.
Mutually exclusive expression of DLX2 and DLX5/6 is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231
Authors: Morini Monica , Astigiano Simonetta , Gitton Yorick , Emionite Laura , Mirisola Valentina , Levi Giovanni , Barbieri Ottavia 
Published: November 2010

Abstract

Background
The DLX gene family encodes for homeobox transcription factors involved in the control of morphogenesis and tissue homeostasis. Their expression can be regulated by Endothelin1 (ET1), a peptide associated with breast cancer invasive phenotype. Deregulation of DLX gene expression was found in human solid tumors and hematologic malignancies. In particular, DLX4 overexpression represents a possible prognostic marker in ovarian cancer. We have investigated the role of DLX genes in human breast cancer progression.

Methods
MDA-MB-231 human breast carcinoma cells were grown in vitro or injected in nude mice, either subcutaneously, to mimic primary tumor growth, or intravenously, to mimic metastatic spreading. Expression of DLX2, DLX5 and DLX6 was assessed in cultured cells, either treated or not with ET1, tumors and metastases by RT-PCR. In situ hybridization was used to confirm DLX gene expression in primary tumors and in lung and bone metastases. The expression of DLX2 and DLX5 was evaluated in 408 primary human breast cancers examining the GSE1456 and GSE3494 microarray datasets. Kaplan-Meier estimates for disease-free survival were calculated for the patients grouped on the basis of DLX2/DLX5 expression.

Results
Before injection, or after subcutaneous growth, MDA-MB-231 cells expressed DLX2 but neither DLX5 nor DLX6. Instead, in bone and lung metastases resulting from intravenous injection we detected expression of DLX5/6 but not of DLX2, suggesting that DLX5/6 are activated during metastasis formation, and that their expression is alternative to that of DLX2. The in vitro treatment of MDA-MB-231 cells with ET1, resulted in switch from DLX2 to DLX5 expression. By data mining in microarray datasets we found that expression of DLX2 occurred in 21.6% of patients, and was significantly correlated with prolonged disease-free survival and reduced incidence of relapse. Instead, DLX5 was expressed in a small subset of cases, 2.2% of total, displaying reduced disease-free survival and high incidence of relapse which was, however, non-significantly different from the other groups due to the small size of the DLX+ cohort. In all cases, we found mutually exclusive expression of DLX2 and DLX5.

Conclusions
Our studies indicate that DLX genes are involved in human breast cancer progression, and that DLX2 and DLX5 genes might serve as prognostic markers.
Outbreak detection algorithms for seasonal disease data: a case study using ross river virus disease
Authors: Pelecanos Anita M , Ryan Peter A , Gatton Michelle L 
Published: November 2010

Abstract

Background
Detection of outbreaks is an important part of disease surveillance. Although many algorithms have been designed for detecting outbreaks, few have been specifically assessed against diseases that have distinct seasonal incidence patterns, such as those caused by vector-borne pathogens.

Methods
We applied five previously reported outbreak detection algorithms to Ross River virus (RRV) disease data (1991-2007) for the four local government areas (LGAs) of Brisbane, Emerald, Redland and Townsville in Queensland, Australia. The methods used were the Early Aberration Reporting System (EARS) C1, C2 and C3 methods, negative binomial cusum (NBC), historical limits method (HLM), Poisson outbreak detection (POD) method and the purely temporal SaTScan analysis. Seasonally-adjusted variants of the NBC and SaTScan methods were developed. Some of the algorithms were applied using a range of parameter values, resulting in 17 variants of the five algorithms.

Results
The 9,188 RRV disease notifications that occurred in the four selected regions over the study period showed marked seasonality, which adversely affected the performance of some of the outbreak detection algorithms. Most of the methods examined were able to detect the same major events. The exception was the seasonally-adjusted NBC methods that detected an excess of short signals. The NBC, POD and temporal SaTScan algorithms were the only methods that consistently had high true positive rates and low false positive and false negative rates across the four study areas. The timeliness of outbreak signals generated by each method was also compared but there was no consistency across outbreaks and LGAs.

Conclusions
This study has highlighted several issues associated with applying outbreak detection algorithms to seasonal disease data. In lieu of a true gold standard, a quantitative comparison is difficult and caution should be taken when interpreting the true positives, false positives, sensitivity and specificity.
Promotion of tumor development in prostate cancer by progerin
Authors: Tang Yong , Chen Yakun , Jiang Hongmei , Nie Daotai 
Published: November 2010

Abstract
Progerin is a truncated form of lamin A. It is identified in patients with Hutchinson-Gilford progeria syndrome (HGPS), a disease characterized by accelerated aging. The contribution of progerin toward aging has been shown to be related to increased DNA damages. Since aging is one major risk factor for carcinogenesis, and genomic instability is a hallmark of malignant cancers, we investigated the expression of progerin in human cancer cells, and whether its expression contributes to carcinogenesis. Using RT-PCR and Western blotting, we detected the expression of progerin in prostate PC-3, DU145 and LNCaP cells at mRNA and protein levels. Ectopic progerin expression did not cause cellular senescence in PC-3 or MCF7 cells. PC-3 cells progerin transfectants were sensitized to DNA damage agent camptothecin (CPT); and persistent DNA damage responses were observed, which might be caused by progerin induced defective DNA damage repair. In addition, progerin transfectants were more tumorigenic in vivo than vector control cells. Our study for the first time describes the expression of progerin in a number of human cancer cell lines and its contributory role in tumorigenesis.
The role of toll-like receptors in acute and chronic lung inflammation
Authors: Lafferty Erin I , Qureshi Salman T , Schnare Markus 
Published: November 2010

AbstractBy virtue of its direct contact with the environment, the lung is constantly challenged by infectious and non-infectious stimuli that necessitate a robust yet highly controlled host response coordinated by the innate and adaptive arms of the immune system. Mammalian Toll-like receptors (TLRs) function as crucial sentinels of microbial and non-infectious antigens throughout the respiratory tract and mediate host innate immunity. Selective induction of inflammatory responses to harmful environmental exposures and tolerance to innocuous antigens are required to maintain tissue homeostasis and integrity. Conversely, dysregulated innate immune responses manifest as sustained and self-perpetuating tissue damage rather than controlled tissue repair. In this article we review aspects of Toll-like receptor function that are relevant to the development of acute lung injury and chronic obstructive lung diseases as well as resistance to frequently associated microbial infections.
Mena deficiency delays tumor progression and decreases metastasis in polyoma middle-T transgenic mouse mammary tumors
Authors: Roussos Evanthia T , Wang Yarong , Wyckoff Jeffrey B , Sellers Rani S , Wang Weigang , Li Jiufeng , Pollard Jeffrey W , Gertler Frank B , Condeelis John S 
Published: November 2010

Abstract
Introduction
The actin binding protein Mammalian enabled (Mena), has been implicated in the metastatic progression of solid tumors in humans. Mena expression level in primary tumors is correlated with metastasis in breast, cervical, colorectal and pancreatic cancers. Cells expressing high Mena levels are part of the tumor microenvironment for metastasis (TMEM), an anatomical structure that is predictive for risk of breast cancer metastasis. Previously we have shown that forced expression of Mena adenocarcinoma cells enhances invasion and metastasis in xenograft mice. Whether Mena is required for tumor progression is still unknown. Here we report the effects of Mena deficiency on tumor progression, metastasis and on normal mammary gland development.

Methods
To investigate the role of Mena in tumor progression and metastasis, Mena deficient mice were intercrossed with mice carrying a transgene expressing the polyoma middle T oncoprotein, driven by the mouse mammary tumor virus. The progeny were investigated for the effects of Mena deficiency on tumor progression via staging of primary mammary tumors and by evaluation of morbidity. Stages of metastatic progression were investigated using an in vivo invasion assay, intravital multiphoton microscopy, circulating tumor cell burden, and lung metastases. Mammary gland development was studied in whole mount mammary glands of wild type and Mena deficient mice.

Results
Mena deficiency decreased morbidity and metastatic dissemination. Loss of Mena increased mammary tumor latency but had no affect on mammary tumor burden or histologic progression to carcinoma. Elimination of Mena also significantly decreased epidermal growth factor (EGF) induced in vivo invasion, in vivo motility, intravasation and metastasis. Non-tumor bearing mice deficient for Mena also showed defects in mammary gland terminal end bud formation and branching.

Conclusions
Deficiency of Mena decreases metastasis by slowing tumor progression and reducing tumor cell invasion and intravasation. Mena deficiency during development causes defects in invasive processes involved in mammary gland development. These findings suggest that functional intervention targeting Mena in breast cancer patients may provide a valuable treatment option to delay tumor progression and decrease invasion and metastatic spread leading to an improved prognostic outcome.
Myeloid-derived suppressor cells in the peripheral blood of cancer patients contain a subset of immature neutrophils with impaired migratory properties
Authors: Brandau Sven , Trellakis Sokratis , Bruderek Kirsten , Schmaltz Dominik , Steller Gabriele , Elian Motaz , Suttmann Henrik , Schenck Marcus , Welling Jürgen , Zabel Peter , Lang Stephan 
Published: November 2010

ABSTRACTIn tumor-bearing mice, immunosuppressive granulocytic and monocytic MDSC have been identified. The identity and function of MDSC in cancer patients are less clear and need further characterization. We analyzed the peripheral blood of 103 patients with HNC, lung cancer, or cancers of bladder and ureter. Based on sedimentation properties in density gradients, a subset of LD-PMN was identified and analyzed. LD-PMN were expanded in the peripheral blood of cancer patients, suppressed proliferation, and IFN-γ production of polyclonally stimulated T cells and thus, qualify as human MDSC. Immunophenotyping and morphological analysis revealed the accumulation of immature PMN in the MDSC fraction. Neutrophilic MDSC showed altered surface marker expression, prolonged survival, and impaired effector functions when compared with conventional, mature PMN of regular density. MDSC displayed markedly reduced chemotaxis toward tumor-conditioned medium and lacked expression of chemokine receptors CXCR1 and CXCR2, which are normally required for PMN extravasation from the bloodstream and subsequent tissue infiltration. Collectively, our data suggest the accumulation and persistence of long-lived, immature granulocytic MDSC with T cell-suppressive function and impaired migratory properties in the peripheral blood of cancer patients.
Regulation of inflammation, autoimmunity, and infection immunity by HVEM-BTLA signaling
Authors: Shui Jr-Wen , Steinberg Marcos W , Kronenberg Mitchell 
Published: November 2010

ABSTRACTThe HVEM, or TNFRSF14, is a membrane-bound receptor known to activate the NF-κB pathway, leading to the induction of proinflammatory and cell survival-promoting genes. HVEM binds several ligands that are capable of mediating costimulatory pathways, predominantly through its interaction with LIGHT (TNFSF14). However, it can also mediate coinhibitory effects, predominantly by interacting with IGSF members, BTLA or CD160. Therefore, it can function like a “molecular switch” for various activating or inhibitory functions. Furthermore, recent studies suggest the existence of bidirectional signaling with HVEM acting as a ligand for signaling through BTLA, which may act as a ligand in other contexts. Bidirectional signaling, together with new information indicating signaling in cis by cells that coexpress HVEM and its ligands, makes signaling within a HVEM-mediated network complicated, although potentially rich in biology. Accumulating in vivo evidence has shown that HVEM-mediated, coinhibitory signaling may be dominant over HVEM-mediated costimulatory signaling. In several disease models the absence of HVEM-BTLA signaling predominantly resulted in severe mucosal inflammation in the gut and lung, autoimmune-like disease, and impaired immunity during bacterial infection. Here, we will summarize the current view about how HVEM-BTLA signaling is involved in the regulation of mucosal inflammation, autoimmunity, and infection immunity.
Glucose-Dependent Insulinotropic Polypeptide (GIP) Induces Calcitonin Gene-Related Peptide (CGRP)-I and Procalcitonin (Pro-CT) Production in Human Adipocytes
Authors: Timper Katharina , Grisouard Jean , Radimerski Tanja , Dembinski Kaethi , Peterli Ralph , Häring Andreas , Frey Daniel M. , Zulewski Henryk , Keller Ulrich , Müller Beat , Christ-Crain Mirjam 
Published: November 2010

abstract

Context:
Increased plasma levels of glucose-dependent insulinotropic polypeptide (GIP), calcitonin CT gene-related peptide (CGRP)-I, and procalcitonin (Pro-CT) are associated with obesity. Adipocytes express functional GIP receptors and the CT peptides Pro-CT and CGRP-I. However, a link between GIP and CT peptides has not been studied yet.

Objective:
The objective of the study was the assessment of the GIP effect on the expression and secretion of CGRP-I and Pro-CT in human adipocytes, CGRP-I and CT gene expression in adipose tissue (AT) from obese vs. lean subjects, and plasma levels of CGRP-I and Pro-CT after a high-fat meal in obese patients.

Design and Participants:
Human preadipocyte-derived adipocytes, differentiated in vitro, were treated with GIP. mRNA expression and protein secretion of CGRP-I and Pro-CT were measured. Human CGRP-I and CT mRNA expression in AT and CGRP-I and Pro-CT plasma concentrations were assessed.

Results:
Treatment with 1 nm GIP induced CGRP-I mRNA expression 6.9 ± 1.0-fold (P &lt; 0.001 vs. control) after 2 h and CT gene expression 14.0 ± 1.7-fold (P &lt; 0.001 vs. control) after 6 h. GIP stimulated CGRP-I secretion 1.7 ± 0.2-fold (P &lt; 0.05 vs. control) after 1 h. In AT samples of obese subjects, CGRP-I mRNA expression was higher in sc AT (P &lt; 0.05 vs. lean subjects), whereas CT expression was higher in visceral AT (P &lt; 0.05 vs. lean subjects). CGRP-I plasma levels increased after a high-fat meal in obese patients.

Conclusion:
GIP induces CGRP-I and CT expression in human adipocytes. Therefore, elevated Pro-CT and CGRP-I levels in obesity might result from GIP-induced Pro-CT and CGRP-I release in AT and might be triggered by a high-fat diet. How these findings relate to the metabolic complications of obesity warrants further investigations.
Memantine Prevents Hypoglycemia-Induced Decrements of the Cerebral Energy Status in Healthy Subjects
Authors: Willenborg B. , Schmoller A. , Caspary J. , Melchert U. H. , Scholand-Engler H. G. , Jauch-Chara K. , Hohagen F. , Schweiger U. , Oltmanns K. M. 
Published: November 2010

abstract

Context:
The risk to develop dementia is significantly increased in diabetes mellitus. Memantine, an N-methyl-d-aspartate receptor antagonist, which is clinically applied in dementia, has been shown to exert neuroprotective effects under hypoglycemic conditions in rats.

Objective:
We hypothesized that memantine may prevent hypoglycemia-induced decrements in the cerebral high-energy phosphate, i.e. ATP, metabolism to exert its neuroprotective action under these conditions.

Design and Participants:
In a randomized, double-blind crossover design, we applied memantine vs. placebo in 16 healthy male subjects and examined the cerebral high-energy phosphate metabolism by 31phosphor magnetic resonance spectroscopy, hormonal counterregulation, and neurocognitive performance during hypoglycemic glucose clamp conditions.

Results:
We found increments in hormonal counterregulation and reduced neurocognitive performance during hypoglycemia (P &lt; 0.05). Cerebral ATP levels increased upon hypoglycemia in the memantine condition as compared with placebo (P = 0.006) and remained higher after renormalizing blood glucose concentrations (P = 0.018), which was confirmed by ATP to inorganic phosphate ratio (P = 0.046). Phosphocreatine levels and phosphocreatine to inorganic phosphate ratio remained stable throughout the experiments and did not differ between conditions (P &gt; 0.1 for both).

Conclusion:
Our data demonstrate that memantine preserves the cerebral energy status during experimentally induced hypoglycemia in healthy subjects. An improved neuronal energy status may thus be involved in the neuroprotective effect under these conditions and may qualify memantine as potential future option to combat cognitive impairments and dementia in diabetes.
How to Construct Chiral Macrocycles from Anthracene Units and Acetylene Linkers
Authors: Toyota Shinji 
Published: November 2010

Abstract
We propose strategies to construct chiral macrocycles by modification of the fundamental compound, 1,8-anthrylene–ethynylene cyclic tetramer, which features a diamond-prism structure. The incorporation of other anthracene units or diacetylene linkers produces structures of various symmetries. The enantiomers of some chiral derivatives could be resolved by chiral HPLC. The structures, dynamic behavior, and chiroptical properties of these macrocycles are summarized.
Polymer Particles Incorporating ZrO2 Nanoparticles Prepared by Miniemulsion Polymerization
Authors: Tamai Toshiyuki , Watanabe Mitsuru , Minami Yuki , Okazaki Sosuke , Masuyama Araki , Matsukawa Kimihiro 
Published: November 2010

Abstract
Acrylic polymer particles incorporating ZrO2 nanoparticles (hybrid latex dispersion) were synthesized by miniemulsion polymerization. The refractive index of the films prepared from the hybrid latex increased with increase of ZrO2 content. Surface-modified ZrO2 nanoparticles could be dispersed in polymer matrix having phosphoric acid group.