bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome Analysis of Agmatine and Putrescine Catabolism inPseudomonas aeruginosaPAO1
Authors: Chou Han Ting , Kwon Dong-Hyeon , Hegazy Mohamed , Lu Chung-Dar
Published: January 2008

Polyamines (putrescine, spermidine, and spermine) are major organic polycations essential for a wide spectrum of cellular processes. The cells require mechanisms to maintain homeostasis of intracellular polyamines to prevent otherwise severe adverse effects. We performed a detailed transcriptome profile analysis ofPseudomonas aeruginosain response to agmatine and putrescine with an emphasis in polyamine catabolism. Agmatine serves as the precursor compound for putrescine (and hence spermidine and spermine), which was proposed to convert into 4-aminobutyrate (GABA) and succinate before entering the tricarboxylic acid cycle in support of cell growth, as the sole source of carbon and nitrogen. Two acetylpolyamine amidohydrolases, AphA and AphB, were found to be involved in the conversion of agmatine into putrescine. Enzymatic products of AphA were confirmed by mass spectrometry analysis. Interestingly, the alanine-pyruvate cycle was shown to be indispensable for polyamine utilization. The newly identifieddadRAXlocus encoding the regulator alanine transaminase and racemase coupled with SpuC, the major putrescine-pyruvate transaminase, were key components to maintaining alanine homeostasis. Corresponding mutant strains were severely hampered in polyamine utilization. On the other hand, an alternative γ-glutamylation pathway for the conversion of putrescine into GABA is present in some organisms. Subsequently, GabD, GabT, and PA5313 were identified for GABA utilization. The growth defect of the PA5313gabTdouble mutant in GABA suggested the importance of these two transaminases. The succinic-semialdehyde dehydrogenase activity of GabD and its induction by GABA were also demonstrated in vitro. Polyamine utilization in general was proven to be independent of the PhoPQ two-component system, even though a modest induction of this operon was induced by polyamines. Multiple potent catabolic pathways, as depicted in this study, could serve pivotal roles in the control of intracellular polyamine levels.
The Chaperone IpgC Copurifies with the Virulence Regulator MxiE
Authors: Pilonieta M. Carolina , Munson George P.
Published: January 2008

The expression of a subset of
Shigella flexneri
virulence genes is dependent upon a cytoplasmic chaperone, IpgC, and an activator from the AraC/XylS family, MxiE. In this paper, we report that the chaperone forms a specific and stable heteromer with MxiE.
A 15-year prospective study of shift work and disability pension: Table 1
Authors: Tüchsen F , Christensen K B , Lund T , Feveile H
Published: January 2008

Objective:

To estimate the hazard ratio for disability pension associated with shift work.

Methods:

Cohorts of shift and day workers were identified in three waves of the Danish Work Environment Cohort Study and followed up for incidence of disability pension in a national register of social transfer payment. A total of 3980 female and 4025 male employees were included in the cohorts. Information about shift work status, age, smoking habits, body mass index and ergonomic work environment were updated according to responses in subsequent waves of the survey when possible. Respondents reporting shift work were classified as shift workers in the following waves as well. Respondents were followed in the register from the time of first interview and were censored at the time of their 60th birthday, emigration, death or end of follow-up (18 June 2006). The authors used the Cox proportional hazards model to estimate hazard ratios for incidence of disability pension and 95% confidence intervals.

Results:

The authors observed 253 new disability pensions among women and 173 among men during 56 903 and 57 886 person-years at risk respectively, Among women, shift work predicted disability after adjustment for age, general health and socioeconomic status HR 1.39 (95% CI 1.07 to 1.82). After further adjustment for body mass index, smoking habits, socioeconomic status and ergonomic exposures the association remained statistically significant HR 1.34 (95% CI 1.02 to 1.75). Shift work was not associated with disability among men.

Conclusion:

Shift work might be moderately associated with disability pension among women; however, more powerful studies are needed to establish the possible association.
Trees of the people: the growing science of poplars in Canada and worldwideThis commentary is one of a selection of papers published in the Special Issue on Poplar Research in Canada.
Authors: Cooke Janice E.K. , Rood Stewart B.
Published: January 2008

Poplars are trees of the angiosperm genus Populus , a group of generally diploid, dioecious, and deciduous pioneers that are widespread in forests around the Northern Hemisphere. Canada is a centre of poplar abundance and diversity, with 7 of the 29 global Populus species occurring naturally, and other species being introduced. Numerous interspecific hybrids also occur, including native hybrids that create centres of biodiversity, and artificial hybrid poplars that are planted for wood and fiber production, as well as for environmental and landscape applications. This paper introduces poplars and their distribution across Canada and explores Canadian and international contributions to poplar research. It also discusses papers of the special issue Poplar Research in Canada in the November 2007 and December 2007 issues of the Canadian Journal of Botany, which contains a collection of 19 contributions from Canadian institutions that report on a diverse range of topics including genomics and molecular biology, physiology, ecology, population genetics, and systematics. Many of these contributions address issues pertinent to silviculture and other applications, and one article chronicles poplar research and poplar utilization in Canada. These studies that appear in this special issue reflect the growing international emphasis on poplar, not only as an important and widespread group of trees, but also as a model that provides broader insights relevant to fundamental and applied sciences involving trees and forest systems.
Impacts of whole-tree harvesting and winter windrowing on soil pH and base status of clayey sites of northwestern Quebec
Authors: Brais S. , Camiré C. , Paré D.
Published: January 2008

To assess the impact of forest operations on soil nutrient status, modifications to forest floor, to 0–10 and 10–20 cm mineral soil base status, and to pH were evaluated 5–12 years following whole-tree harvesting and winter windrowing on dry to fresh and moist clayey sites in the clay belt region of northwestern Quebec. Whole-tree harvesting had few impacts on base concentrations and soil pH of dry to fresh sites. On moist sites, significant decreases in pH (−0.60 to −0.84 units), exchangeable Ca, total Ca, and, exchangeable Mg concentrations, base saturation, and effective cation exchange capacity were observed following harvesting. On dry to fresh sites, a decrease in the forest floor weight (−55%) accounted for significant reductions in exchangeable Ca (−55%), total Ca (−61%), and exchangeable K (−40%) pools in this layer, while reserves of both mineral layers were not affected. On moist sites, significant decreases in exchangeable Ca (−42 to −65%) and Mg (−35 to −56%) reserves occurred in all soil layers, while forest floor reserves of total Ca, Mg, and K decreased by 67, 48, and 40%, respectively. These reductions were caused by a loss of substrate in the forest floor (−44%) and a decrease in effective cation exchange capacity, exchangeable Ca saturation, and total Ca concentrations. Impacts of windrowing following whole-tree harvesting were limited to a reduction in reserves of exchangeable Ca (−22%), exchangeable Mg (−27%), total Ca (−20%), and total Mg (−29%) pools of the forest floor of moist sites. Values reported here are much greater than values generally predicted by a balance sheet approach and underline the need for more process-oriented studies. Impacts of these losses on long-term site productivity remain to be investigated.
PROBABILITY IN RELATIVISTIC QUANTUM MECHANICS AND FOLIATION OF SPACE–TIME
Authors: NIKOLIĆ HRVOJE
Published: January 2008

The conserved probability densities (attributed to the conserved currents derived from relativistic wave equations) should be nonnegative and the integral of them over an entire hypersurface should be equal to one. To satisfy these requirements in a covariant manner, the foliation of space–time must be such that each integral curve of the current crosses each hypersurface of the foliation once and only once. In some cases, it is necessary to use hypersurfaces that are not spacelike everywhere. The generalization to the many-particle case is also possible.
MICROTUBULES AS ACTIVE TRACKS FOR BI-DIRECTIONAL CELLULAR TRAFFIC OF MOTOR PROTEINS
Authors: SATARIĆ M. V. , BUDINSKI-PETKOVIĆ LJ. , LONČAREVIĆ I.
Published: January 2008

The basic cytoskeletal transport in cells is achieved by two oppositely directed processive motor proteins, kinesin and dynein, walking along microtubules. Here, we offer a new view of the mechanism of the transport direction regulation by the intrinsic cell's electric fields that interact with kinks elicited in microtubules.
IMPACT OF LASER IRRADIATION ON THE MAGNETO-OPTICAL PROPERTIES OF HYBRID MULTILAYER FILM STRUCTURES
Authors: KRUPA M. M. , KOROSTIL A. M.
Published: January 2008

The influence of nanosecond laser impulse irradiation on the magneto-optical properties of multilayer film nanostructures Bi – SiC – TbFe – SiC , SiC – TbFe – SiC , SiC – Tb – Au – Fe – SiC , and phthalocyanine dye–bismuth–phthalocyanine dye was investigated. It was shown that this irradiation causes the injection of spin-polarized electrons from magnetic into nonmagnetic layers of the multilayer films. Nonequilibrium magnetization arising in nonmagnetic layers leads to the change of magneto-optical characteristics. The voltage induced by laser irradiation can also produce a directed drift of Bi ions toward the laser beam action.
Caffeine induces hyperacetylation of histones at the MEF2 site on theGlut4promoter and increases MEF2A binding to the site via a CaMK-dependent mechanism
Authors: Mukwevho Emmanuel , Kohn Tertius A. , Lang Dirk , Nyatia Edward , Smith James , Ojuka Edward O.
Published: January 2008

This study was conducted to explore the mechanism by which caffeine increases GLUT4 expression in C2C12myotubes. Myoblasts were differentiated in DMEM containing 2% horse serum for 13 days and the resultant myotubes exposed to 10 mM caffeine in the presence or absence of 25 μM KN93 or 10 mM dantrolene for 2 h. After the treatment, cells were kept in serum-free medium and harvested between 0 and 6 h later, depending on the assay. Chromatin immunoprecipitation (ChIP) assays revealed that caffeine treatment caused hyperacetylation of histone H3 at the myocyte enhancer factor 2 (MEF2) site on the Glut4 promoter ( P < 0.05) and increased the amount of MEF2A that was bound to this site ∼2.2-fold ( P < 0.05) 4 h posttreatment compared with controls. These increases were accompanied by an ∼1.8-fold rise ( P < 0.05 vs. control) in GLUT4 mRNA content at 6 h post-caffeine treatment. Both immunoblot and immunocytochemical analyses showed reduced nuclear content of histone deacetylase-5 in caffeine-treated myotubes compared with controls at 0–2 h posttreatment. Inclusion of 10 mM dantrolene in the medium to prevent the increase in cytosolic Ca2+, or 25 μM KN93 to inhibit Ca2+/calmodulin-dependent protein kinase (CaMK II), attenuated all the above caffeine-induced changes. These data indicate that caffeine increases GLUT4 expression by acetylating the MEF2 site to increase MEF2A binding via a mechanism that involves CaMK II.
Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active Gαo* protein
Authors: Zhu Ming , Gach Agnieszka A. , Liu GongXin , Xu Xiaomei , Lim Chee Chew , Zhang Julie X. , Mao Lan , Chuprun Kurt , Koch Walter J. , Liao Ronglih , Koren Gideon , Blaxall Burns C. , Mende Ulrike
Published: January 2008

In contrast to the other heterotrimeric GTP-binding proteins (G proteins) Gsand Gi, the functional role of Gois still poorly defined. To investigate the role of Gαoin the heart, we generated transgenic mice with cardiac-specific expression of a constitutively active form of Gαo1* (Gαo*), the predominant Gαoisoform in the heart. Gαoexpression was increased 3- to 15-fold in mice from 5 independent lines, all of which had a normal life span and no gross cardiac morphological abnormalities. We demonstrate enhanced contractile function in Gαo* transgenic mice in vivo, along with increased L-type Ca2+channel current density, calcium transients, and cell shortening in ventricular Gαo*-expressing myocytes compared with wild-type controls. These changes were evident at baseline and maintained after isoproterenol stimulation. Expression levels of all major Ca2+handling proteins were largely unchanged, except for a modest reduction in Na+/Ca2+exchanger in transgenic ventricles. In contrast, phosphorylation of the ryanodine receptor and phospholamban at known PKA sites was increased 1.6- and 1.9-fold, respectively, in Gαo* ventricles. Density and affinity of β-adrenoceptors, cAMP levels, and PKA activity were comparable in Gαo* and wild-type myocytes, but protein phosphatase 1 activity was reduced upon Gαo* expression, particularly in the vicinity of the ryanodine receptor. We conclude that Gαo* exerts a positive effect on Ca2+cycling and contractile function. Alterations in protein phosphatase 1 activity rather than PKA-mediated phosphorylation might be involved in hyperphosphorylation of key Ca2+handling proteins in hearts with constitutive Gαoactivation.
Deletion of the mouse α-calcitonin gene-related peptide gene increases the vulnerability of the heart to ischemia-reperfusion injury
Authors: Huang Ruiping , Karve Amrita , Shah Ibrahim , Bowers Mark C. , DiPette Donald J. , Supowit Scott C. , Abela George S.
Published: January 2008

Calcitonin gene-related peptide (CGRP), a potent vasodilator released from capsaicin-sensitive C-fiber and Aδ-fiber sensory nerves, has been suggested to play a beneficial role in myocardial ischemia-reperfusion (I/R) injury. Because most previous studies showing a cardioprotective role of CGRP employed pharmacological experiments, the purpose of this study was to utilize a genetic approach by using mice with a targeted deletion of the α-CGRP gene to determine whether this neuropeptide had a modulatory function on the severity of I/R injury. To accomplish this goal, isolated, perfused hearts from α-CGRP knockout (KO) and wild-type (WT) mice were subjected to 30 min of ischemia followed by 5, 15, and 30 min of reperfusion. Cardiac functional parameters, including coronary flow rates, left ventricular developed pressure, maximum rates of pressure development, and left ventricular end-diastolic pressure, were measured before and after I/R injury, as were levels of creatine kinase, to assess myocardial damage, and malonaldehyde, to assess oxidative stress. Following I/R injury, cardiac performance was significantly reduced in the hearts from the α-CGRP KO mice compared with their WT counterparts. The marked reduction in myocardial function in the α-CGRP KO hearts compared with WT hearts after I/R injury was associated with a significant elevation in creatine kinase release into the perfusates and malonaldehyde production in the cardiac tissue. Therefore, these data indicate that, in this in vitro setting, deletion of α-CGRP makes the heart more vulnerable to I/R injury, possibly due, at least in part, to increased oxidative stress.
Role of sarcolemmal ATP-sensitive potassium channel in oxidative stress-induced apoptosis: mitochondrial connection
Authors: Marinovic Jasna , Ljubkovic Marko , Stadnicka Anna , Bosnjak Zeljko J. , Bienengraeber Martin
Published: January 2008

From time of their discovery, sarcolemmal ATP-sensitive K+(sarcKATP) channels were thought to have an important protective role in the heart during stress whereby channel opening protects the heart from stress-induced Ca2+overload and resulting damage. In contrast, some recent studies indicate that sarcKATPchannel closing can lead to cardiac protection. Also, the role of the sarcKATPchannel in apoptotic cell death is unclear. In the present study, the effects of channel inhibition on apoptosis and the specific interaction between the sarcKATPchannel and mitochondria were investigated. Apoptotic cell death of cultured HL-1 and neonatal cardiomyocytes following exposure to oxidative stress was significantly increased in the presence of sarcKATPchannel inhibitor HMR-1098 as evidenced by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and caspase-3,7 assays. This was paralleled by an increased release of cytochrome c from mitochondria to cytosol, suggesting activation of the mitochondrial death pathway. sarcKATPchannel inhibition during stress had no effect on Bcl-2, Bad, and phospho-Bad, indicating that the increase in apoptosis cannot be attributed to these modulators of the apoptotic pathway. However, monitoring of mitochondrial Ca2+with rhod-2 fluorescent indicator revealed that mitochondrial Ca2+accumulation during stress is potentiated in the presence of HMR-1098. In conclusion, this study provides novel evidence that opening of sarcKATPchannels, through a specific Ca2+-related interaction with mitochondria, plays an important role in preventing cardiomyocyte apoptosis and mitochondrial damage during stress.
Genomic structure, transcriptional control, and tissue distribution ofHERG1andKCNQ1genes
Authors: Luo Xiaobin , Xiao Jiening , Lin Huixian , Lu Yanjie , Yang Baofeng , Wang Zhiguo
Published: January 2008

The long QT syndrome genes human ether-a-go-go-related gene ( HERG1) and voltage-gated K+channel, KQT-like subfamily, member 1, gene ( KCNQ1), encoding K+channels critical to the repolarization rate and repolarization reserve in cardiac cells, and thereby the likelihood of arrhythmias, are both composed of two isoforms: HERG1a and HERG1b and KCNQ1a and KCNQ1b, respectively. Expression of these genes is dynamic, depending on the differentiation status and disease states. We identified their core promoter regions and transcription start sites. Our data suggest that HERG1a and HERG1b, and KCNQ1a and KCNQ1b, represent independent transcripts instead of being alternatively spliced variants of the same gene, for they each have their own transcription start sites and their own promoter regions. We obtained data pointing to the potential role of stimulating protein 1 (Sp1) in the transactivation of these genes. We compared expression profiling of these genes across a variety of human tissues. Consistent with the general lack of cis elements for cardiac-specific transcription factors and the presence of multiple sites for ubiquitous Sp1 sites in the core promoter regions of HERG1a/HERG1b and KCNQ1a/KCNQ1b genes, the transcripts demonstrated widespread distribution across a variety of human tissues. We further revealed that the mRNA levels of all HERG1 and KCNQ1 isoforms were asymmetrically distributed within the heart, being more abundant in the right atria and ventricles relative to the left atria and ventricles. These findings open up an opportunity for studying interventricular gradients of slow and rapid delayed rectifier K+current and of cardiac repolarization as well. Our study might help us understand the molecular mechanisms for arrhythmias since heterogeneity of ion channel activities is an important substrate for arrhythmogenesis.
Spontaneous baroreflex control of heart rate versus cardiac output: altered coupling in heart failure
Authors: Sala-Mercado Javier A. , Ichinose Masashi , Hammond Robert L. , Coutsos Matthew , Ichinose Tomoko , Pallante Marco , Iellamo Ferdinando , O'Leary Donal S.
Published: January 2008

Dynamic cardiac baroreflex responses are frequently investigated by analyzing the spontaneous reciprocal changes in arterial pressure and heart rate (HR). However, whether the spontaneous baroreflex-induced changes in HR translate into changes in cardiac output (CO) is unknown. In addition, this linkage between changes in HR and changes in CO may be different in subjects with heart failure (HF). We examined these questions using conscious dogs before and after pacing-induced HF. Spontaneous baroreflex sensitivity in the control of HR and CO was evaluated as the slopes of the linear relationships between HR or CO and left ventricular systolic pressure (LVSP) during spontaneous sequences of greater or equal to three consecutive beats when HR or CO changed inversely versus pressure. Furthermore, the translation of baroreflex HR responses into CO responses (HR-CO translation) was examined by computing the overlap between HR and CO sequences. In normal resting conditions, 44.0 ± 4.4% of HR sequences overlapped with CO sequences, suggesting that only around half of the baroreflex HR responses cause CO responses. In HF, HR-LVSP, CO-LVSP, and the HR-CO translation significantly decreased compared with the normal condition (−2.29 ± 0.5 vs. −5.78 ± 0.7 beats·min−1·mmHg−1; −70.95 ± 11.8 vs. −229.89 ± 29.6 ml·min−1·mmHg−1; and 19.66 ± 4.9 vs. 44.0 ± 4.4%, respectively). We conclude that spontaneous baroreflex HR responses do not always cause changes in CO. In addition, HF significantly decreases HR-LVSP, CO-LVSP, and HR-CO translation.
Increased pulmonary vascular resistance and defective pulmonary artery filling in caveolin-1−/−mice
Authors: Maniatis Nikolaos A. , Shinin Vasily , Schraufnagel Dean E. , Okada Shigenori , Vogel Stephen M. , Malik Asrar B. , Minshall Richard D.
Published: January 2008

Caveolin-1, the structural and signaling protein of caveolae, is an important negative regulator of endothelial nitric oxide synthase (eNOS). We observed that mice lacking caveolin-1 ( Cav1−/−) had twofold increased plasma NO levels but developed pulmonary hypertension. We measured pulmonary vascular resistance (PVR) and assessed alterations in small pulmonary arteries to determine the basis of the hypertension. PVR was 46% greater in Cav1−/−mice than wild-type (WT), and increased PVR in Cav1−/−mice was attributed to precapillary sites. Treatment with NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NOS activity raised PVR by 42% in WT but 82% in Cav1−/−mice, indicating greater NO-mediated pulmonary vasodilation in Cav1−/−mice compared with WT. Pulmonary vasculature of Cav1−/−mice was also less reactive to the vasoconstrictor thromboxane A2mimetic (U-46619) compared with WT. We observed redistribution of type I collagen and expression of smooth muscle α-actin in lung parenchyma of Cav1−/−mice compared with WT suggestive of vascular remodeling. Fluorescent agarose casting also showed markedly decreased density of pulmonary arteries and artery filling defects in Cav1−/−mice. Scanning electron microscopy showed severely distorted and tortuous pulmonary precapillary vessels. Thus caveolin-1 null mice have elevated PVR that is attributed to remodeling of pulmonary precapillary vessels. The elevated basal plasma NO level in Cav1−/−mice compensates partly for the vascular structural abnormalities by promoting pulmonary vasodilation.
Cleavage of high-molecular-weight kininogen by elastase and tryptase is inhibited by ferritin
Authors: Coffman Lan G. , Brown Julie C. , Johnson David A. , Parthasarathy Narayanan , D'Agostino Ralph B. , Lively Mark O. , Hua Xiaoyang , Tilley Stephen L. , Muller-Esterl Werner , Willingham Mark C. , Torti Frank M. , Torti Suzy V.
Published: January 2008

Ferritin is a protein principally known for its role in iron storage. We have previously shown that ferritin can bind high-molecular-weight kininogen (HK). Upon proteolytic cleavage by the protease kallikrein, HK releases the proinflammatory peptide bradykinin (BK) and other biologically active products, such as two-chain high-molecular-weight kininogen, HKa. At inflammatory sites, HK is oxidized, which renders it a poor substrate for kallikrein. However, oxidized HK remains a good substrate for elastase and tryptase, thereby providing an alternative cleavage mechanism for HK during inflammation. Here we report that ferritin can retard the cleavage of both native HK and oxidized HK by elastase and tryptase. Initial rates of cleavage were reduced 45–75% in the presence of ferritin. Ferritin is not a substrate for elastase or tryptase and does not interfere with the ability of either protease to digest a synthetic substrate, suggesting that ferritin may impede HK cleavage through direct interaction with HK. Immunoprecipitation and solid phase binding studies reveal that ferritin and HK bind directly with a Kdof 134 nM. To test whether ferritin regulates HK cleavage in vivo, we used THP-1 cells, a human monocyte/macrophage cell line that has been used to model pulmonary inflammatory cells. We observed that ferritin impedes the cleavage of HK by secretory proteases in stimulated macrophages. Furthermore, ferritin, HK, and elastase are all present in or on alveolar macrophages in a mouse model of pulmonary inflammation. Collectively, these results implicate ferritin in the modulation of HK cleavage at sites of inflammation.
Induction of Cancer Metastasis by Cyclophosphamide Pretreatment of Host Mice: An Opposite Effect of Chemotherapy
Authors: Yamauchi Kensuke , Yang Meng , Hayashi Katsuhiro , Jiang Ping , Yamamoto Norio , Tsuchiya Hiroyuki , Tomita Katsuro , Moossa Abdool R. , Bouvet Michael , Hoffman Robert M.
Published: January 2008

Although side effects of cancer chemotherapy are well known, “opposite effects” of chemotherapy that enhance the malignancy of the treated cancer are not well understood. In this report, we describe the induction of intravascular proliferation, extravasation, and colony formation by cancer cells, critical steps of metastasis, by pretreatment of host mice with the commonly used chemotherapy drug cyclophosphamide. In contrast, in the unpretreated mice, most cancer cells remained quiescent in vessels without extravasation. HT1080 human fibrosarcoma cells, labeled in the nucleus with green fluorescent protein and red fluorescent protein in the cytoplasm for imaging, were injected into the epigastric cranialis vein of nude mice. Twenty-four hours before cancer cell injection, cyclophosphamide was given i.p. Double-labeled cancer cells were imaged at the cellular level in live mice with the Olympus OV100 Small Animal Imaging System with variable magnification. Cyclophosphamide seems to interfere with a host process that inhibits intravascular proliferation, extravasation, and extravascular colony formation. Cyclophosphamide does not directly affect the cancer cells because cyclophosphamide has been cleared by the time the cancer cells were injected. This report shows an important unexpected “opposite effect” of chemotherapy that enhances critical steps in malignancy rather than inhibiting them, suggesting that certain current approaches to cancer chemotherapy should be modified. [Cancer Res 2008;68(2):516–20]
Sputum Cytologic Atypia Predicts Incident Lung Cancer: Defining Latency and Histologic Specificity
Authors: Byers Tim , Wolf Holly J. , Franklin Wilbur A. , Braudrick Sarah , Merrick Daniel T. , Shroyer Kenneth R. , Hirsch Fred R. , Zeng Chan , Barón Anna E. , Bunn Paul A. , Miller York E. , Kennedy Timothy C.
Published: January 2008

Background: There is a need for early detection methods for lung cancer. Radiologic imaging may be more sensitive for peripheral cancers than for cancers arising in the central airways, from which bronchial epithelial cells are exfoliated into the sputum.

Methods: Sputum samples were collected at baseline and periodically thereafter in a cohort of smokers and former smokers with chronic obstructive lung disease. The association between cytologic atypia and incident lung cancer was assessed by hazard ratios (HR; 95% confidence intervals) using Cox regression and by odds ratios (95% confidence intervals) using logistic regression, adjusting for potential confounding factors.

Results: We observed 174 incident lung cancers in a cohort of 2,521 people over 9,869 person-years of observation. Risk for incident lung cancer was increased among those with cytologic atypia graded as moderate or worse (adjusted HR, 2.37; 1.68-3.34). The association between sputum atypia and lung cancer incidence was greatest for those sputum samples collected 5 months or less before the diagnosis of lung cancer (odds ratio, 10.32; 5.34-19.97). The association was substantially stronger for squamous cell lung cancers (HR, 5.13; 2.89-9.10) than for adenocarcinomas (HR, 1.85; 0.94-3.65).

Conclusion: Cytologic atypia is a marker for increased lung cancer risk. These cytologic changes seem to arise from late events that are most apparent for cancers arising in the central respiratory airways. Whether cytologic atypia might complement radiologic imaging in a combined approach to lung cancer, early detection requires additional evaluation of those two methods used together. (Cancer Epidemiol Biomarkers Prev 2008;17(1):158–63)
Profiling Tumor-Associated Markers for Early Detection of Malignant Mesothelioma: An Epidemiologic Study
Authors: Amati Monica , Tomasetti Marco , Scartozzi Mario , Mariotti Laura , Alleva Renata , Pignotti Elettra , Borghi Battista , Valentino Matteo , Governa Mario , Neuzil Jiri , Santarelli Lory
Published: January 2008

Improved detection methods for diagnosis of asymptomatic malignant mesothelioma (MM) are essential for an early and reliable detection and treatment of this type of neoplastic disease. Thus, focus has been on finding tumor markers in the blood that can be used for noninvasive detection of MM. Ninety-four asbestos-exposed subjects defined at high risk, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the clinical significance of 8-hydroxy-2′-deoxyguanosine (8OHdG) in WBCs and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors [platelet-derived growth factor β, hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor β (VEGFβ)], and matrix proteases [matrix metalloproteinase (MMP) 2, MMP9, tissue inhibitor of metalloproteinase (TIMP) 1, and TIMP2] for potential early detection of MM. The area under receiver operating characteristic (ROC) curves indicate that 8OHdG levels can discriminate asbestos-exposed subjects from healthy controls but not from MM patients. Significant area under ROC curve values were found for SMRPs, discriminating asbestos-exposed subjects from MM patients but not from healthy controls. Except for platelet-derived growth factor β, the hepatocyte growth factor, basic fibroblast growth factor, and VEGFβ can significantly differentiate high-risk individuals from healthy control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, and TIMP2. In addition to the diagnostic performance defined by the ROC analysis, the sensitivity and specificity results of markers with clinical significance were calculated at defined cutoffs. The combination of 8OHdG, VEGFβ, and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations. (Cancer Epidemiol Biomarkers Prev 2008;17(1):163–70)
Exfoliated Buccal Mucosa Cells as a Source of DNA to Study Oxidative Stress
Authors: Borthakur Gayatri , Butryee Chaniphun , Stacewicz-Sapuntzakis Maria , Bowen Phyllis E.
Published: January 2008

The extent of oxidative DNA damage is considered a biomarker of carcinogenic process and could be investigated in population studies using easily obtained cells. The oxidized DNA base adduct 8-hydroxy-2-deoxyguanosine (8-OHdG) released by enzymatic hydrolysis of DNA is commonly assayed by high performance liquid chromatography with electrochemical detection. It is expressed as a ratio of 8-OHdG to unoxidized deoxyguanosine. We modified and improved this method, determined the optimal time for harvesting buccal mucosa cells (BMC), assessed whether they mirror peripheral circulating blood cell DNA damage, and compared the anticoagulants, heparin, and EDTA for consistency in measurement of leukocyte 8-OHdG. Thirty-one healthy participants, randomized into two groups, donated BMC and blood samples. Samples were collected at baseline and either 3 or 7 days after baseline. Results showed no correlation between 8-OHdG/deoxyguanosine ratios in BMC and peripheral blood leukocytes at any time point regardless of harvest time. BMC had much higher oxidative DNA damage, but displayed a 25.6% reduction in the oxidized DNA adduct level (P < 0.04) at 3 days after baseline. Leukocytes collected in heparin and EDTA had similar 8OHdG/deoxyguanosine ratios; however, EDTA was preferred, as it produced a clean nuclear pellet without hemoglobin contamination, and the results were less variable. This improved assay shows within subject stability over time in both leukocyte and BMC DNA damage, increasing the probability that small intervention differences can be detected in healthy subjects. Buccal cells provide an accessible pool of epithelial cells that represents higher levels of DNA damage than circulating leukocytes. (Cancer Epidemiol Biomarkers Prev 2008;17(1):212–9)
Glomus Tumor of the Stomach Simulating a Gastrointestinal Stromal Tumor: A Case Report and Review of Literature
Authors: Matevossian Edouard , Brücher Björn L.D.M. , Nährig Jörg , Feuβner Hubertus , Hüser Norbert
Published: January 2008

Glomus tumor is an infrequent and in most cases benign mesenchymal neoplasia which affects subcutaneous/submucosal tissue and occurs in the gastrointestinal tract, solid organs (e.g. liver, kidney) and the extremities. Visceral glomus tumor of the stomach generally presents with non-specific epigastric pain, loss of appetite and GI bleeding (melaena), often without haemodynamic instability. Macroscopic appearances on upper GI endoscopy are non-diagnostic. Endosonographic appearances are generally heterogenous and poorly-reflective, hence fail to differentiate glomus tumor from other potential diagnoses. Histological confirmation of the diagnosis is only possible when a fine needle biopsy is inclusive of abnormal tissue. These difficulties in diagnosis mean that in many cases, only immunohistochemical analysis of surgically resected tissue can distinguish glomus tumor from several possible differentials. Therefore, endoscopically-assisted laparoscopic curative wedge-resection of a lesion suspicious for glomus tumor of the upper gastrointestinal tract must be considered first-line in terms of a combined investigative and curative approach.
Properties of the Wind Field within the Oklahoma City Park Avenue Street Canyon. Part I: Mean Flow and Turbulence Statistics
Authors: Nelson M. A. , Pardyjak E. R. , Klewicki J. C. , Pol S. U. , Brown M. J.
Published: January 2008

Velocity data were obtained from sonic anemometer measurements within an east–west-running street canyon located in the urban core of Oklahoma City, Oklahoma, during the Joint Urban 2003 field campaign. These data were used to explore the directional dependence of the mean flow and turbulence within a real-world street canyon. The along-canyon vortex that is a key characteristic of idealized street canyon studies was not evident in the mean wind data, although the sensor placement was not optimized for the detection of such structures. Instead, surface wind measurements imply that regions of horizontal convergence and divergence exist within the canopy, which are likely caused by taller buildings diverting the winds aloft down into the canopy. The details of these processes appear to be dependent on relatively small perturbations in the prevailing wind direction. Turbulence intensities within the canyon interior appeared to have more dependence on prevailing wind direction than they did in the intersections. Turbulence in the intersections tended to be higher than was observed in the canyon interior. This behavior implies that there are some fundamental differences between the flow structure found in North American–style cities where building heights are typically heterogeneous and that found in European-style cities, which generally have more homogeneous building heights. It is hypothesized that the greater three-dimensionality caused by the heterogeneous building heights increases the ventilation of the urban canopy through mean advective transport as well as enhanced turbulence.
The Aberrant Anterior Tibial Artery
Authors: Klecker Rosemary J. , Winalski Carl S. , Aliabadi Piran , Minas Tom
Published: January 2008

Background

Injury of a popliteal fossa artery during orthopaedic knee surgery is very rare but has serious consequences. The risk of vascular trauma during orthopaedic procedures may be increased when there is abnormal branching of the popliteal artery with an aberrant anterior tibial artery originating above the popliteus muscle and coursing between the posterior tibial cortex and ventral margin of the popliteus muscle. Preoperative identification of this anatomical variant may help avoid these injuries.

Hypothesis

The aberrant anterior tibial artery is present in a substantial portion of the population and can be visualized by magnetic resonance imaging.

Study Design

Cross-sectional study; Level of evidence, 3.

Methods

Retrospective review of 1116 consecutive knee magnetic resonance imaging studies was performed to evaluate the prevalence of an aberrant anterior tibial artery. Images were reviewed by 3 musculoskeletal radiologists.

Results

The aberrant anterior tibial artery was present in 23 of 1116 extremities for a prevalence of 2.1 %. The aberrant artery was most easily identified on axial and sagittal magnetic resonance imaging scans.

Conclusion

The aberrant anterior tibial artery is a relatively common normal variant, and magnetic resonance is an excellent modality for detection of the artery close to the posterior joint capsule and tibial cortex.

Clinical Relevance

The anatomy suggests the aberrant anterior tibial artery may be at greater risk of injury in orthopaedic procedures such as high tibial osteotomy, revision total knee arthroplasty, lateral meniscal repair, posterior cruciate ligament reconstruction, and screw fixation for tibial tubercle osteotomy. Careful inspection of preoperative magnetic resonance imaging studies may alert the surgeon to the presence of this anatomical variant.
A Randomized Controlled Trial Comparing the Effectiveness of Functional Knee Brace and Neoprene Sleeve Use after Anterior Cruciate Ligament Reconstruction
Authors: Birmingham Trevor B. , Bryant Dianne M. , Giffin J. Robert , Litchfield Robert B. , Kramer John F. , Donner Allan , Fowler Peter J.
Published: January 2008

Background

Despite a lack of evidence for their effectiveness, functional knee braces are commonly prescribed to patients after anterior cruciate ligament (ACL) reconstruction.

Purpose

This trial was conducted to compare postoperative outcomes in patients using an ACL functional knee brace and patients using a neoprene knee sleeve.

Hypothesis

Patients using a brace will have superior outcomes than those using a sleeve.

Study Design

Randomized controlled clinical trial; Level of evidence, 1.

Methods

One hundred fifty patients were randomized to receive a brace (n = 76) or neoprene sleeve (n = 74) at their 6-week postoperative visit after primary ACL reconstruction with hamstring autograft. Patients were assessed preoperatively, then 6 weeks and 6, 12, and 24 months postoperatively. Outcome measures included disease-specific quality of life (Anterior Cruciate Ligament–Quality of Life [ACL-QOL] Questionnaire), anterior tibial translation (KT-1000 arthrometer side-to-side difference), the single-limb forward hop test (limb symmetry index), and Tegner Activity Scale. Outcomes at 1 and 2 years were compared after adjusting for baseline scores. Subjective ratings of how patients felt while using the brace/sleeve were also collected for descriptive purposes using a questionnaire. Four a priori directional subgroup hypotheses were evaluated using tests for interactions.

Results

There were no significant differences between brace (n = 62) and sleeve (n = 65) groups for any of the outcomes at 1- and 2-year follow-ups. Adjusted mean differences at 2 years were as follows: −0.94 (95% confidence interval [CI], −7.52 to 5.64) for the ACL-QOL Questionnaire, −0.10 mm (95% CI, −0.99 to 0.81) for KT-1000 arthrometer side-to-side difference, −0.87% (95% CI, −8.89 to 7.12) for hop limb symmetry index, and −0.05 (95% CI, −0.72 to 0.62) for the Tegner Activity Scale. Subjective ratings of confidence in the knee provided by the brace/sleeve were higher for the brace group than the sleeve group. Subgroup findings were minimal. Adverse events were few and similar between groups.

Conclusions

A functional knee brace does not result in superior outcomes compared with a neoprene sleeve after ACL reconstruction. Current evidence does not support the recommendation of using an ACL functional knee brace after ACL reconstruction.
Childhood Orbital Pseudotumor: Case Report and Literature Review
Authors: Kitei Dan , DiMario Francis J.
Published: January 2008

Orbital pseudotumor, also known as idiopathic orbital inflammation, is a benign, idiopathic, noninfectious, and nonneoplastic clinical syndrome with an inflammatory mass within the orbit and no identifiable cause. This disease is rare in the pediatric population, especially in very young children. In this article, the authors describe a 2-year-old girl who was presented with right eye ptosis, near-complete ophthalmoplegia, decreased visual acuity, and pupillary changes. She recovered completely with high-dose steroid therapy. The authors review the literature and discuss the diagnostic implications and treatment strategies.
Sudden-Onset Ptosis Caused by Midbrain Neurocysticercosis in 2 Children
Authors: Singhi Pratibha , Mahajan Vikas , Khandelwal N.K.
Published: January 2008

Neurocysticercosis is the most common parasitic infestation of the central nervous system, which manifests commonly as acute-onset focal seizures. We report a rare nonepileptic manifestation of neurocysticercosis: midbrain neurocysticercosis presenting as sudden-onset ptosis in 2 children. To our knowledge, this has not been reported previously in children.
Diagnostic Yield of Brain Biopsies in Children Presenting to Neurology
Authors: Venkateswaran Sunita , Hawkins Cynthia , Wassmer Evangeline
Published: January 2008

The role of brain biopsy is well established in patients with neoplastic lesions, with a diagnostic yield approaching 95%. The diagnostic yield of brain biopsy in adults with neurological decline varies from 20% to 43%. Only a few studies have examined the diagnostic yield of brain biopsy in children with idiopathic neurological decline. A retrospective analysis was conducted on all open and closed pediatric brain biopsies performed between January 1988 and May 2003. Biopsies were performed for diagnostic purposes in patients showing a progressively deteriorating neurologic course in whom less-invasive modalities such as neuroimaging, electroencephalography (EEG), and molecular genetic studies were either negative or inconclusive. Immunocompromised patients were included. Patients were excluded if the preoperative diagnosis was a neoplasm or if the patient was undergoing a resection as part of a work-up for intractable epilepsy. Each patient underwent numerous investigations before brain biopsy. The utility of each biopsy was analyzed. Sixty-six children had brain biopsies performed for diagnostic purposes during the study period. Patient ages ranged from 2 months to 16 years and 9 months at the time of biopsy. The diagnostic yield was 48.5% overall, with a yield of 68.8% between 1996 and 2003. Of the total, 26 (39.4%) biopsies were both diagnostic and useful. Patients most frequently presented with seizures (56.1%) and encephalopathy (33%). The most frequently diagnosed disease was vasculitis (18.2%). A total of 71.9% of patients with diagnostic biopsies improved with appropriate treatment. Brain biopsy in children had a diagnostic yield of 48.5% in our series. A specific diagnosis may help in management and outcome, especially with a diagnosis of vasculitis.
“We Are Here to Give You Emotional Support”: Performing Emotions in an Online HIV/AIDS Support Group
Authors: Bar-Lev Shirly
Published: January 2008

Since the advent of the Internet, social critics have debated its effects on intimacy and social relationships. I show how, by writing detailed descriptions of their illness experiences, participants in online support groups create emotionally vibrant, empathic communities in which emotional rhetoric frames various moral dilemmas. I illustrate my argument with a detailed analysis of “emotion talk” among members of an HIV/AIDS support group over a 2-year period. My findings add to current debates by encouraging sociologists to consider the emotional dynamics within the online support group as a moral, rather than just psychological or therapeutic, component of interaction.
Symptoms of ADHD and Academic Concerns in College Students With and Without ADHD Diagnoses
Authors: Lewandowski Lawrence J. , Lovett Benjamin J. , Codding Robin S. , Gordon Michael
Published: January 2008

Objective: Previous research has found ADHD symptoms to be common in the general population but has not compared endorsement of symptoms between ADHD and non-ADHD groups. This study examines self-reported ADHD symptoms and academic complaints in college students. Method: Students without ( n = 496) and with ADHD ( n = 38) completed a questionnaire covering the 18 ADHD symptoms in the Diagnostic and Statistical Manual of Mental Disorders and academic and test-taking concerns. Results and Conclusion: Students with ADHD diagnoses reported significantly more ADHD symptoms and academic concerns, but none of the 18 symptoms or 6 concerns proved to be both sensitive and specific to ADHD. Poor specificity of symptoms and academic complaints casts doubt on the utility of this self-reported information in diagnosis, particularly if used alone and without regard to severity or extent of impairment. (J. of Att. Dis. 2008; 12(2) 156-161)
Flavopiridol causes early mitochondrial damage in chronic lymphocytic leukemia cells with impaired oxygen consumption and mobilization of intracellular calcium
Authors: Hussain Syed-Rehan A. , Lucas David M. , Johnson Amy J. , Lin Thomas S. , Bakaletz Alan P. , Dang Vinh X. , Viatchenko-Karpinski Serge , Ruppert Amy S. , Byrd John C. , Kuppusamy Periannan , Crouser Elliott D. , Grever Michael R.
Published: January 2008

Effective administration of flavopiridol in advanced-stage chronic lymphocytic leukemia (CLL) is often associated with early biochemical evidence of tumor cell lysis. Previous work using other cell types showed that flavopiridol impacts mitochondria, and in CLL cells flavopiridol down-regulates the mitochondrial protein Mcl-1. We therefore investigated mitochondrial structure and function in flavopiridol-treated CLL patient cells and in the lymphoblastic cell line 697 using concentrations and times at which tumor lysis is observed in treated patients. Mitochondrial membrane depolarization was detected in flavopiridol-treated CLL cells by 6 hours, well before the onset of cell death. Flavopiridol-induced mitochondrial depolarization was not blocked by caspase inhibitors or by the calcium chelator EGTA, but was reduced by Bcl-2 overexpression. Intracellular calcium mobilization was noted at early time points using fluorescence microscopy. Furthermore, electron paramagnetic resonance oximetry showed a gradual but significant reduction in cellular oxygen consumption rate by 6 hours, corresponding with ultrastructural mitochondrial damage detected by electron microscopy. These observations suggest that in CLL and 697 cells, flavopiridol mediates its cytotoxic effects via induction of the mitochondrial permeability transition and changes in intracellular calcium.