bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of work related asthma: results from a population based survey
Authors: Breton C V , Zhang Z , Hunt P R , Pechter E , Davis L 
Published: February 2006

Objectives:Many risk factors for asthma have been investigated, one of which is the workplace. Work related asthma is a frequently reported occupational respiratory disease yet the characteristics which distinguish it from non-work related asthma are not well understood. The purpose of this study was to examine differences between work related and non-work related asthma with respect to healthcare use and asthma control characteristics.Methods:Data from the Massachusetts Behavioral Risk Factor Surveillance System for 2001 and 2002 were used for this analysis. Work related status of asthma was determined by self-report of ever having been told by a physician that asthma was work related. Healthcare measures evaluated were emergency room visits and physician visits for worsening asthma and for routine care. Characteristics of asthma control evaluated were frequency of asthma symptoms, asthma attacks, difficulty sleeping, and asthma medication usage in the last 30 days and limited activity in the past 12 months.Results:The prevalence of lifetime and current asthma in Massachusetts were 13.0% and 9.2%, respectively. Approximately 6.0% (95% CI 4.8 to 7.3) of lifetime and 6.2% (95% CI 4.7 to 7.8) of current asthma cases were work related. In the past 12 months, individuals with work related current asthma were 4.8 times (95% CI 2.0 to 11.6) as likely to report having an asthma attack, 4.8 times (95% CI 1.8 to 13.1) as likely to visit the emergency room at least once, and 2.5 times (95% CI 1.1 to 6.0) as likely to visit the doctor at least once for worsening asthma compared to individuals with non-work related asthma.Conclusions:Work related asthma is associated with increased frequency of asthma attacks and use of healthcare services. A better understanding of factors that contribute to differences in healthcare use and asthma control is needed to improve prevention and control strategies for individuals suffering from the disease.
Cancer mortality in German carbon black workers 1976–98
Authors: Wellmann J , Weiland S K , Neiteler G , Klein G , Straif K 
Published: February 2006

Background:Few studies have investigated cancer risks in carbon black workers and the findings were inconclusive.Methods:The current study explores the mortality of a cohort of 1535 male German blue-collar workers employed at a carbon black manufacturing plant for at least one year between 1960 and 1998. Vital status and causes of death were assessed for the period 1976–98. Occupational histories and information on smoking were abstracted from company records. Standardised mortality ratios (SMR) and Poisson regression models were calculated.Results:The SMRs for all cause mortality (observed deaths (obs) 332, SMR 120, 95% CI 108 to 134), and mortality from lung cancer (obs 50, SMR 218, 95% CI 161 to 287) were increased using national rates as reference. Comparisons to regional rates from the federal state gave SMRs of 120 (95% CI 107 to 133) and 183 (95% CI 136 to 241), respectively. However, there was no apparent dose response relationship between lung cancer mortality and several indicators of occupational exposure, including years of employment and carbon black exposure.Conclusions:The mortality from lung cancer among German carbon black workers was increased. The high lung cancer SMR can not fully be explained by selection, smoking, or other occupational risk factors, but the results also provide little evidence for an effect of carbon black exposure.
Low Levels of α7-Nicotinic Acetylcholine Receptor mRNA on Peripheral Blood Lymphocytes in Schizophrenia and Its Association with Illness Severity
Authors: Perl Orly , Strous Rael D. , Dranikov Angela , Chen Rina , Fuchs Sara 
Published: February 2006

<i>Background:</i> There is evidence that the nicotinic α7-acetylcholine receptor (α7-AChR) is involved in the pathophysiology of schizophrenia. Several neurotransmitter receptors, including α7-AChR, have been demonstrated on peripheral blood lymphocytes (PBL) and it has been suggested that these peripheral receptors may reflect corresponding brain receptors. <i>Objective:</i> In this study we compare α7 mRNA expression in PBL between schizophrenia patients and control individuals in order to determine whether any correlation exists between α7 mRNA expression in PBL and severity of schizophrenia. In addition, the isoforms of α7-AChR expressed are identified. <i>Method:</i> Peripheral venous blood samples were collected from individuals with schizophrenia (n = 44) and from healthy subjects (n = 16). Symptomatology and illness severity were assessed using standard clinical psychiatric evaluation scales. RNA was prepared from isolated lymphocytes and DELETE α7 mRNA was measured by RT-PCR. <i>Results:</i> We observed a significantly lower level of α7 mRNA on PBLs of schizophrenia patients incomparison with healthy controls (p < 0.00). A tendency to a negative correlation was noted between the CGI score, reflecting illness severity, and the α7-subunit gene expression. <i>Conclusion:</i> Observations confirm that the α7 mRNA in PBL represents the duplicated α7-AChR gene rather than the classic α7-AChR gene. Our study observations further substantiate the involvement of α7-AChR in the pathophysiology of schizophrenia and, while preliminary, indicate that the α7-AChR may be expressed and be readily measured in the peripheral blood circulation.
Advanced Oxidation Protein Products Accelerate Atherosclerosis Through Promoting Oxidative Stress and Inflammation
Authors: Liu Shang Xi , Hou Fan Fan , Guo Zhi Jian , Nagai Ryoji , Zhang Wei Ru , Liu Zhi Qiang , Zhou Zhan Mei , Zhou Mei , Xie Di , Wang Guo Bao , Zhang Xun 
Published: February 2006

Objective—Increased level of plasma advanced oxidation protein products (AOPPs) has been found in patients with uremia and nonuremic subjects with coronary artery disease. This study was conducted to test the hypothesis that AOPPs play a causal role in atherosclerosis.Methods and Results—Hypercholesterolemic (0.5% wt/wt diet) or normal rabbits received either repeated intravenous injections of AOPPs modified rabbit serum albumin (AOPPs-RSA) or unmodified RSA for 8 weeks. Compared with RSA- or vehicle-treated hypercholesterolemic rabbits, AOPPs-RSA–treated animals displayed increased atherosclerotic plaque area oxidized low-density lipoprotein (oxLDL) deposition, macrophage infiltration, and smooth muscle cell proliferation. Aortic sections from AOPPs-RSA–treated normal rabbits showed significant focal intima proliferation and mild Oil-Red-O staining lipid deposition in the affected areas, a phenomenon not observed in the RSA- or vehicle-treated controls. Plasma AOPPs levels in AOPPs-treated groups significantly increased in both hypercholesterolemic and normal rabbits compared with their relevant controls. Close correlations were found between plasma levels of AOPPs and the parameters of oxidative stress, eg, oxLDL and thiobarbituric acid reactive substances levels, or glutathione peroxidase activity. A highly significant correlation was also observed between plasma AOPPs and tumor necrosis factor (TNF)-α levels.Conclusions—This study provides in vivo evidence for a causal relationship between chronic AOPPs accumulation and atherosclerosis.
Homocysteine Activates cAMP-response Element Binding Protein in HepG2 Through cAMP/PKA Signaling Pathway
Authors: Woo Connie W.H. , Siow Yaw L. , O Karmin 
Published: February 2006

Objective—Hyperhomocysteinemia is an independent risk factor for cardiovascular disorders. Our previous studies demonstrated that hyperhomocysteinemia not only elicited inflammatory responses in the vascular endothelium but also induced fatty liver and hypercholesterolemia via transcriptional regulation. One of the transcription factors activated in the liver during hyperhomocysteinemia was cAMP-response element binding protein (CREB). CREB regulates the expression of many genes including those involved in lipid and glucose metabolism. In this study, we investigated the molecular mechanism by which Hcy activated CREB in rat liver and in hepatocytes (HepG2).Method and Results—Hyperhomocysteinemia was induced in rats by feeding high-methionine diet for 4 weeks. There was a significant increase in hepatic cAMP levels, protein kinase A (PKA) activity and an activation of CREB. Incubation of HepG2 cells with Hcy (50 to 100 μmol/L) significantly enhanced CREB phosphorylation and subsequently increased CREB/DNA binding activity. PKA was activated in Hcy-treated cells as a result of increased cellular cAMP level. Inhibition of adenylyl cyclase not only reduced the intracellular cAMP levels elevated by Hcy treatment but also inhibited PKA activation and prevented Hcy-induced CREB phosphorylation.Conclusion—These results suggest that the cAMP/PKA signaling pathway plays an important role in mediating Hcy-induced CREB activation in hepatocyte.
A common phosphotyrosine signature for the Bcr-Abl kinase
Authors: Goss Valerie L. , Lee Kimberly A. , Moritz Albrecht , Nardone Julie , Spek Erik J. , MacNeill Joan , Rush John , Comb Michael J. , Polakiewicz Roberto D. 
Published: February 2006

AbstractThe Bcr-Abl fusion kinase drives oncogenesis in chronic myeloid leukemia (CML). CML patients are currently treated with the Abl tyrosine kinase inhibitor imatinib, which is effective in early stages of the disease. However, resistance to imatinib arises in later disease stages primarily because of a Bcr-Abl mutation. To gain deeper insight into Bcr-Abl signaling pathways, we generated phosphotyrosine profiles for 6 cell lines that represent 3 Bcr-Abl fusion types by using immunoaffinity purification of tyrosine phosphopeptides followed by tandem mass spectrometry. We identified 188 nonredundant tyrosine-phosphorylated sites, 77 of which are novel. By comparing the profiles, we found a number of phosphotyrosine sites common to the 6 cell lines regardless of cellular background and fusion type, several of which are decreased by imatinib treatment. Comparison of this Bcr-Abl signature with the profile of cells expressing an alternative imatinib-sensitive fusion kinase, FIP1L1-PDGFRα, revealed that these kinases signal through different pathways. This phosphoproteomic study of the Bcr-Abl fusion kinase highlights novel disease markers and potential drug-responsive biomarkers and adds novel insight into the oncogenic signals driven by the Bcr-Abl kinase.
Overexpression of survivin in primary ATL cells and sodium arsenite induces apoptosis by down-regulating survivin expression in ATL cell lines
Authors: Che Xiao-Fang , Zheng Chun-Lei , Owatari Satsuki , Mutoh Masato , Gotanda Takenari , Jeung Hei-Cheul , Furukawa Tatsuhiko , Ikeda Ryuji , Yamamoto Masatatsu , Haraguchi Misako , Arima Naomichi , Akiyama Shin-ichi 
Published: February 2006

AbstractPatients with acute- or lymphoma-type adult T-cell leukemia (ATL) have a poor outcome because of the intrinsic drug resistance to chemotherapy. Protection from apoptosis is a common feature involved in multidrug-resistance of ATL. IAP (inhibitor of apoptosis) family proteins inhibit apoptosis induced by a variety of stimuli. In this study, we investigated the expression of IAP family members (survivin, cIAP1, cIAP2, and XIAP) in the primary leukemic cells from patients with ATL. We found that survivin was overexpressed in ATL, especially in acute-type ATL. Sodium arsenite was shown to down-regulate the expression of survivin at both the protein and RNA levels in a time- and dose-dependent manner, thus inhibiting cell growth, inducing apoptosis, and enhancing the caspase-3 activity in ATL cells. Nuclear factor-κB (NF-κB) enhances the transcriptional activity of survivin. Sodium arsenite suppressed the constitutive NF-κB activation by preventing the IκB-α degradation and the nuclear translocation of NF-κB. These findings suggest that survivin is an important antiapoptotic molecule that confers drug resistance on ATL cells. Sodium arsenite was shown to down-regulate the expression of survivin through the NF-κB pathway, thus inhibiting cell growth and promoting apoptosis of ATL cells.
Identification of the angiogenic endothelial-cell growth factor-1/thymidine phosphorylase as a potential target for immunotherapy of cancer
Authors: Slager Elisabeth H. , Honders M. Willy , van der Meijden Edith D. , van Luxemburg-Heijs Simone A. P. , Kloosterboer Freke M. , Kester Michel G. D. , Jedema Inge , Marijt W. A. Erik , Schaafsma M. Ron , Willemze Roel , Falkenburg J. H. Frederik 
Published: February 2006

AbstractCharacterization of the antigens recognized by tumor-reactive T cells isolated from patients successfully treated with allogeneic HLA-matched hematopoietic stem cell transplantation (SCT) can lead to the identification of clinically relevant target molecules. We isolated tumor-reactive cytotoxic CD8+ T-cell (CTL) clones from a patient successfully treated with donor lymphocyte infusion for relapsed multiple myeloma after allogeneic HLA-matched SCT. Using cDNA expression cloning, the target molecule of an HLA-B7–restricted CTL clone was identified. The CTL clone recognized a minor histocompatibility antigen produced by a single nucleotide polymorphism (SNP) in the angiogenic endothelial-cell growth factor-1 (ECGF1) gene also known as thymidine phosphorylase. The SNP leads to an Arg-to-His substitution in an alternatively translated peptide that is recognized by the CTL. The ECGF1 gene is predominantly expressed in hematopoietic cells, although low expression can also be detected in other tissues. The patient from whom this CTL clone was isolated had mild graft-versus-host disease despite high numbers of circulating ECGF-1–specific T cells as detected by tetramer staining. Because solid tumors expressing ECGF-1 could also be lysed by the CTL, ECGF-1 is an interesting target for immunotherapy of both hematologic and solid tumors.
Oncogenic RAS mutations in myeloma cells selectively induce cox-2 expression, which participates in enhanced adhesion to fibronectin and chemoresistance
Authors: Hoang Bao , Zhu Li , Shi Yijiang , Frost Patrick , Yan Huajun , Sharma Sanjai , Sharma Sherven , Goodglick Lee , Dubinett Steven , Lichtenstein Alan 
Published: February 2006

AbstractOncogenic RAS expression occurs in up to 40% of multiple myeloma (MM) cases and correlates with aggressive disease. Since activated RAS induces cyclooxygenase-2 (cox-2) expression in other tumor models, we tested a role for cox-2 in mutant RAS–containing MM cells. We used the ANBL-6 isogenic MM cell lines in which the IL-6–dependent parental line becomes cytokine independent following transfection with mutated N-RAS or K-RAS. Both mutated N-RAS– and K-RAS–expressing ANBL-6 cells demonstrated a selective up-regulation of cox-2 expression and enhanced secretion of PGE2, a product of cox-2. Furthermore, in 3 primary marrow specimens, which contained MM cells expressing mutated RAS, 15% to 40% of tumor cells were positive for cox-2 expression by immunohistochemistry. We used cox-2 inhibitors, NS398 and celecoxib, and neutralizing anti-PGE2 antibody to test whether cox-2/PGE2 was involved in the aggressive phenotype of MM ANBL-6 cells containing mutated RAS. Although these interventions had no effect on IL-6–independent growth or adhesion to marrow stromal cells, they significantly inhibited the enhanced binding of mutant RAS– containing MM cells to fibronectin and the enhanced resistance to melphalan. These results indicate a selective induction of cox-2 in MM cells containing RAS mutations, which results in heightened binding to extracellular matrix protein and chemotherapeutic drug resistance.
IL-10–producing macrophages preferentially clear early apoptotic cells
Authors: Xu Wei , Roos Anja , Schlagwein Nicole , Woltman Andrea M. , Daha Mohamed R. , van Kooten Cees 
Published: February 2006

AbstractEfficient clearance of apoptotic cells seems to be a prerequisite to prevent the development of autoimmunity. Here we identify that macrophage colony-stimulating factor (M-CSF)–driven macrophages (Mø2s) are potent phagocytes that have the unique capacity to preferentially bind and ingest early apoptotic cells. This macrophage subset has intrinsic anti-inflammatory properties, characterized by high interleukin-10 (IL-10) production in the absence of proinflammatory cytokines, such as IL-6 and tumor necrosis factor-α (TNF-α). Importantly, whereas the IL-6 and TNF-α production by granulocyte-macrophage (GM)–CSF–driven macrophages (Mø1s) is inhibited upon uptake of apoptotic cells, the anti-inflammatory status of Mø2 is retained during phagocytosis. Mø2s were shown to use CD14 to tether apoptotic cells, whereas recognition of phosphatidylserine (PS) contributed to uptake of early apoptotic cells. Mø2s showed more potent macropinocytosis compared with dendritic cells (DCs) and Mø1s, and uptake of apoptotic cells was inhibited by a macropinocytosis inhibitor. Our studies suggest that, under steady-state conditions, IL-10–producing Mø2s are prominently involved in the clearance of early apoptotic cells.
Endotoxin induced peritonitis elicits monocyte immigration into the lung: implications on alveolar space inflammatory responsiveness
Authors: Steinmüller Mirko , Srivastava Mrigank , Kuziel William A , Christman John W , Seeger Werner , Welte Tobias , Lohmeyer Jürgen , Maus Ulrich A 
Published: February 2006

Abstract

Background
Acute peritonitis developing in response to gram-negative bacterial infection is known to act as a trigger for the development of acute lung injury which is often complicated by the development of nosocomial pneumonia. We hypothesized that endotoxin-induced peritonitis provokes recruitment of monocytes into the lungs, which amplifies lung inflammatory responses to a second hit intra-alveolar challenge with endotoxin.

Methods
Serum and lavage cytokines as well as bronchoalveolar lavage fluid cells were analyzed at different time points after intraperitoneal or intratracheal application of LPS.

Results
We observed that mice challenged with intraperitoneal endotoxin developed rapidly increasing serum and bronchoalveolar lavage fluid (BALF) cytokine and chemokine levels (TNFα, MIP-2, CCL2) and a nearly two-fold expansion of the alveolar macrophage population by 96 h, but this was not associated with the development of neutrophilic alveolitis. In contrast, expansion of the alveolar macrophage pool was not observed in CCR2-deficient mice and in wild-type mice systemically pretreated with the anti-CD18 antibody GAME-46. An intentional two-fold expansion of alveolar macrophage numbers by intratracheal CCL2 following intraperitoneal endotoxin did not exacerbate the development of acute lung inflammation in response to intratracheal endotoxin compared to mice challenged only with intratracheal endotoxin.

Conclusion
These data, taken together, show that intraperitoneal endotoxin triggers a CCR2-dependent de novo recruitment of monocytes into the lungs of mice but this does not result in an accentuation of neutrophilic lung inflammation. This finding represents a previously unrecognized novel inflammatory component of lung inflammation that results from endotoxin-induced peritonitis.
Pulmonary vasoconstrictor action of KCNQ potassium channel blockers
Authors: Joshi Shreena , Balan Prabhu , Gurney Alison M 
Published: February 2006

AbstractBackgroundKCNQ channels have been widely studied in the nervous system, heart and inner ear, where they have important physiological functions. Recent reports indicate that KCNQ channels may also be expressed in portal vein where they are suggested to influence spontaneous contractile activity. The biophysical properties of K+currents mediated by KCNQ channels resemble a current underlying the resting K+conductance and resting potential of pulmonary artery smooth muscle cells. We therefore investigated a possible role of KCNQ channels in regulating the function of pulmonary arteries by determining the ability of the selective KCNQ channel blockers, linopirdine and XE991, to promote pulmonary vasoconstriction.MethodsThe tension developed by rat and mouse intrapulmonary or mesenteric arteries was measured using small vessel myography. Contractile responses to linopirdine and XE991 were measured in intact and endothelium denuded vessels. Experiments were also carried out under conditions that prevent the contractile effects of nerve released noradrenaline or ATP, or block various Ca2+influx pathways, in order to investigate the mechanisms underlying contraction.ResultsLinopirdine and XE991 both contracted rat and mouse pulmonary arteries but had little effect on mesenteric arteries. In each case the maximum contraction was almost as large as the response to 50 mM K+. Linopirdine had an EC50of around 1 μM and XE991 was almost 10-fold more potent. Neither removal of the endothelium nor exposure to phentolamine or α,β-methylene ATP, to block α1-adrenoceptors or P2X receptors, respectively, affected the contraction. Contraction was abolished in Ca2+-free solution and in the presence of 1 μM nifedipine or 10 μM levcromakalim.ConclusionThe KCNQ channel blockers are potent and powerful constrictors of pulmonary arteries. This action may be selective for the pulmonary circulation as mesenteric arteries showed little response. The results imply that the drugs act directly on smooth muscle cells and contraction requires voltage-dependent Ca2+influx. It is concluded that the drugs probably act by blocking KCNQ channels in pulmonary artery myocytes, leading to membrane depolarization and Ca2+influx through L-type Ca2+channels. This implies a functional role for KCNQ channels in regulating the resting membrane potential of pulmonary artery myocytes.