tbuckley/cabot-search huggingface dataset:
Prescribed fenoterol and death from asthma in New Zealand, 1981-7: a further case-control study.
Authors: J Grainger, K Woodman, N Pearce, J Crane, C Burgess, A Keane, R Beasley
Journal: Thorax (1991)

The association between inhaled fenoterol and death from asthma has been investigated further by studying 112 asthma deaths (cases) during 1981-7 in patients aged 5-45 years who had been admitted to a major hospital for asthma during the 12 months before death. Two age matched control groups were chosen. Control group A comprised 427 patients who had been admitted to hospital for asthma during the calendar year that the corresponding death occurred and who had also had a previous admission for asthma in the previous 12 months. Control group B comprised 448 patients admitted to hospital for asthma during the calendar year in which the admission of the corresponding case occurred. The inhaled fenoterol odds ratio was 2.11 (95% confidence interval (CI) 1.37-3.23, p less than 0.01) when group A was used as the control (the approach used in previous studies), and 2.66 (95% CI 1.74-4.06, p less than 0.01) with group B as the control (the approach recommended by critics of previous studies). Markers of chronic asthma severity were associated with asthma death when control group B was used, but not when control group A was used (which indicates that these markers were indirectly matched for when control group A was used). Information was also collected on various markers of acute asthma severity and prescription of psychotropic drugs, but it was found that these were not important confounders. These findings address the major criticisms of previous case-control studies of this issue, and add support to the hypothesis that inhaled fenoterol increases the risk of death in patients with severe asthma.
Critical role of histone demethylase RBP2 in human gastric cancer angiogenesis
Authors: Lupeng Li, Lixiang Wang, Ping Song, Xue Geng, Xiuming Liang, Minran Zhou, Yangyang Wang, Chunyan Chen, Jihui Jia, Jiping Zeng
Journal: Molecular Cancer (2014)

The molecular mechanisms responsible for angiogenesis and abnormal expression of angiogenic factors in gastric cancer, including vascular endothelial growth factor (VEGF), remain unclear. The histone demethylase retinoblastoma binding protein 2 (RBP2) is involved in gastric tumorgenesis by inhibiting the expression of cyclin-dependent kinase inhibitors (CDKIs).The expression of RBP2, VEGF, CD31, CD34 and Ki67 was assessed in 30 human gastric cancer samples and normal control samples. We used quantitative RT-PCR, western blot analysis, ELISA, tube-formation assay and colony-formation assay to characterize the change in VEGF expression and associated biological activities induced by RBP2 silencing or overexpression. Luciferase assay and ChIP were used to explore the direct regulation of RBP2 on the promoter activity of VEGF. Nude mice and RBP2-targeted mutant mice were used to detect the role of RBP2 in VEGF expression and angiogenesis in vivo.RBP2 and VEGF were both overexpressed in human gastric cancer tissue, with greater microvessel density (MVD) and cell proliferation as compared with normal tissue. In gastric epithelial cell lines, RBP2 overexpression significantly promoted the expression of VEGF and the growth and angiogenesis of the cells, while RBP2 knockdown had the reverse effect. RBP2 directly bound to the promoter of VEGF to regulate its expression by histone H3K4 demethylation. The subcutis of nude mice transfected with BGC-823 cells with RBP2 knockdown showed reduced VEGF expression and MVD, with reduced carcinogenesis and cell proliferation. In addition, the gastric epithelia of RBP2 mutant mice with increased H3K4 trimethylation showed reduced VEGF expression and MVD.The promotion of gastric tumorigenesis by RBP2 was significantly associated with transactivation of VEGF expression and elevated angiogenesis. Overexpression of RBP2 and activation of VEGF might play important roles in human gastric cancer development and progression.
Isopentenyl Pyrophosphate–Activated CD56+ γδ T Lymphocytes Display Potent Antitumor Activity toward Human Squamous Cell Carcinoma
Authors: Alan A.Z. Alexander, Amudhan Maniar, Jean-Saville Cummings, Andrew M. Hebbeler, Dan H. Schulze, Brian R. Gastman, C. David Pauza, Scott E. Strome, Andrei I. Chapoval
Journal: Clinical Cancer Research (2008)

The expression of CD56, a natural killer cell-associated molecule, on alphabeta T lymphocytes correlates with their increased antitumor effector function. CD56 is also expressed on a subset of gammadelta T cells. However, antitumor effector functions of CD56(+) gammadelta T cells are poorly characterized.To investigate the potential effector role of CD56(+) gammadelta T cells in tumor killing, we used isopentenyl pyrophosphate and interleukin-2-expanded gammadelta T cells from peripheral blood mononuclear cells of healthy donors.Thirty to 70% of expanded gammadelta T cells express CD56 on their surface. Interestingly, although both CD56(+) and CD56(-) gammadelta T cells express comparable levels of receptors involved in the regulation of gammadelta T-cell cytotoxicity (e.g., NKG2D and CD94), only CD56(+) gammadelta T lymphocytes are capable of killing squamous cell carcinoma and other solid tumor cell lines. This effect is likely mediated by the enhanced release of cytolytic granules because CD56(+) gammadelta T lymphocytes expressed higher levels of CD107a compared with CD56(-) controls following exposure to tumor cell lines. Lysis of tumor cell lines is blocked by concanamycin A and a combination of anti-gammadelta T-cell receptor + anti-NKG2D monoclonal antibody, suggesting that the lytic activity of CD56(+) gammadelta T cells involves the perforin-granzyme pathway and is mainly gammadelta T-cell receptor/NKG2D dependent. Importantly, CD56-expressing gammadelta T lymphocytes are resistant to Fas ligand and chemically induced apoptosis.Our data indicate that CD56(+) gammadelta T cells are potent antitumor effectors capable of killing squamous cell carcinoma and may play an important therapeutic role in patients with head and neck cancer and other malignancies.
Association Between Method of Delivery and Maternal Rehospitalization
Authors: Mona Lydon-Rochelle
Journal: JAMA (2000)

ContextDespite nearly 4 million deliveries in the United States each year, minimal information exists on unintended health consequences following childbirth, particularly in relation to delivery method.ObjectiveTo assess the risk for maternal rehospitalization associated with cesarean or assisted vaginal delivery compared with spontaneous vaginal delivery.DesignRetrospective cohort study of data from the Washington State Birth Events Record Database for 1987 through November 1, 1996.Setting and ParticipantsAll primiparous women without selected chronic medical conditions who delivered live singleton infants in nonfederal short-stay hospitals in Washington State (N=256,795).Main Outcome MeasuresRelative risks (RRs) of rehospitalization within 60 days of cesarean or assisted vaginal vs spontaneous vaginal deliveries.ResultsA total of 3149 women (1.2%) were rehospitalized within 60 days of delivery. In logistic regression analyses adjusting for maternal age, rehospitalization was found to be more likely among women with cesarean delivery (RR, 1.8; 95% confidence interval [CI], 1.6-1.9) or assisted vaginal delivery (RR, 1.3; 95% CI, 1.2-1.4) than among women with spontaneous vaginal delivery. Cesarean delivery was associated with significantly increased risks of rehospitalization for uterine infection, obstetrical surgical wound complications, and cardiopulmonary and thromboembolic conditions. Among women with assisted vaginal delivery, significant increased risks were seen for rehospitalization with postpartum hemorrhage, obstetrical surgical wound complications, and pelvic injury.ConclusionsWomen with cesarean and assisted vaginal deliveries were at increased risk for rehospitalization, particularly with infectious morbidities. Effective strategies for preventing and controlling peripartum infection should be an obstetrical priority.
Maternal selenium status in pregnancy, glutathione peroxidase 4 genotype and childhood asthma
Authors: Seif Shaheen, Clare Rutterford, Sarah Lewis, Susan Ring, John Holloway, Jean Golding, John Henderson
Journal: European Respiratory Journal (2014)

Two previous studies have suggested that higher prenatal selenium exposure may decrease the risk of wheezing in early childhood. We aimed to test whether higher maternal selenium status in pregnancy is associated with a decreased risk of childhood asthma, and whether this association is modified by glutathione peroxidase  (GPX) 4  genotype.  In the Avon Longitudinal Study of Parents and Children (ALSPAC) we analysed associations between maternal blood concentrations of selenium during pregnancy and childhood asthma (n=2409) and wheezing (n=2438) at 7 years of age. We also explored interactions between maternal selenium and  GPX4  genotype (rs713041) on these outcomes.  After controlling for confounders, maternal blood selenium concentration was not associated with offspring asthma or wheezing overall. When we stratified by child  GPX4  genotype, maternal selenium was not associated with these outcomes in children who carried the C allele of rs713041, however, in children who were homozygous for the minor T allele, maternal selenium was negatively associated with asthma (adjusted odds ratio per doubling concentration 0.15 (95% CI: 0.04 to 0.63), P=0.010) and wheezing (OR 0.16 (0.04 to 0.66), P=0.011), P interaction 0.059 and 0.013, respectively. Conversely, children of mothers in the bottom quintile for blood selenium concentration were more likely to have asthma than children of mothers with higher selenium status, but only if the children were homozygous for the T allele of rs713041 (OR 2.40 (1.07 to 5.41)).  Higher maternal selenium status in pregnancy is associated with a decreased risk of asthma in offspring who are homozygous for the T allele of the rs713041 polymorphism of  GPX4 .
<i>UGT1A1</i> Polymorphism Can Predict Hematologic Toxicity in Patients Treated with Irinotecan
Authors: Jean-François Côté, Sylvain Kirzin, Andrew Kramar, Jean-François Mosnier, Marie-Danièle Diebold, Isabelle Soubeyran, Anne-Sophie Thirouard, Janick Selves, Pierre Laurent-Puig, Marc Ychou
Journal: Clinical Cancer Research (2007)

Irinotecan (CPT-11) is approved in metastatic colorectal cancer treatment and can cause severe toxicity. The main purpose of our study was to assess the role of different polymorphisms on the occurrence of hematologic toxicities and disease-free survival in high-risk stage III colon cancer patients receiving 5-fluorouracil (5FU) and CPT-11 adjuvant chemotherapy regimen in a prospective randomized trial.Four hundred patients were randomized in a phase III trial comparing LV5FU2 to LV5FU2 + CPT-11. DNA from 184 patients was extracted and genotyped to detect nucleotide polymorphism: 3435C>T for ABCB1, 6986A>G for CYP3A5, UGT1A1*28 and -3156G>A for UGT1A1.Genotype frequencies were similar in both treatment arms. In the test arm, no significant difference was observed in toxicity or disease-free survival for ABCB1 and CYP3A5 polymorphisms. UGT1A1*28 homozygous patients showed more frequent severe hematologic toxicity (50%) than UGT1A1*1 homozygous patients (16.2%), P = 0.06. Moreover, patients homozygous for the mutant allele of -3156G>A UGT1A1 polymorphism showed more frequent severe hematologic toxicity (50%) than patients homozygous for wild-type allele (12.5%), P = 0.01. This toxicity occurred significantly earlier in homozygous mutant than wild-type homozygous patients (P = 0.043). In a Cox model, the hazard ratio for severe hematologic toxicity is significantly higher for patients with the A/A compared with the G/G genotype [hazard ratio, 8.4; 95% confidence interval, 1.9-37.2; P = 0.005].This study supports the clinical utility of identification of UGT1A1 promoter polymorphisms before LV5FU2 + CPT-11 treatment to predict early hematologic toxicity. The -3156G>A polymorphism seems to be a better predictor than the UGT1A1 (TA)(6)TAA>(TA)(7)TAA polymorphism.
Persistent γ-herpesvirus Infections
Authors: Marcia A. Blackman, Emilio Flaño
Journal: The Journal of Experimental Medicine (2002)

The human γ-herpesviruses, EBV (or HHV-4) and Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) are oncogenic viruses that induce a readily controlled lytic infection followed by the establishment of life-long latency. This quiescent state is maintained by the host immune system. In most
Angiopoietin-related growth factor antagonizes obesity and insulin resistance
Authors: Yuichi Oike, Masaki Akao, Kunio Yasunaga, Toshimasa Yamauchi, Tohru Morisada, Yasuhiro Ito, Takashi Urano, Yoshishige Kimura, Yoshiaki Kubota, Hiromitsu Maekawa, Takeshi Miyamoto, Keishi Miyata, Shun-ichiro Matsumoto, Juro Sakai, Naomi Nakagata, Motohiro Takeya, Haruhiko Koseki, Yoshihiro Ogawa, Takashi Kadowaki, Toshio Suda
Journal: Nature Medicine (2005)
Normal and abnormal consequences of apoptosis in the human heart. From postnatal morphogenesis to paroxysmal arrhythmias.
Authors: T N James
Journal: Circulation (1994)

Apoptosis and necrosis are two distinctly different forms of cell death, and both occur in the human heart. In contrast to necrosis, apoptosis is not associated with inflammation for two reasons. First, the apoptotic cell does not swell or rupture before it is engulfed by either a macrophage or even a neighboring like cell. Second, the phagocytosis occurs with unusual rapidity. Apoptosis, also thought of as cell suicide, is a tidy way of removing cells no longer useful, in essence a form of selective deletion. These features make apoptosis a valuable component of morphogenesis, mediation of hormonal and immunologic responses, and the homeostatic balance between hypertrophy and atrophy or involution. In the human heart apoptosis has been found in the sinus node of patients with the long QT syndrome. It most likely participates in the important postnatal morphogenesis of the sinus node, AV node, and His bundle. Apoptosis may also participate in the genesis and pathophysiology of cardiomyopathy, paroxysmal arrhythmias, or conduction disturbances (some of which may be responsible for sudden death), focal fibromuscular dysplasia of small coronary arteries, hereditary medial degeneration of the tunica media of coronary arteries, and arrhythmogenic right ventricular dysplasia. The possible role apoptosis in numerous other changes in the human heart, among them the pathogenesis of atherosclerosis and mechanisms of aging in the myocardium, merits future investigation.
Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial
Authors: Dan Stark, Matthew Nankivell, Eric Pujade-Lauraine, Gunnar Kristensen, Lorraine Elit, Martin Stockler, Felix Hilpert, Andrés Cervantes, Julia Brown, Anne Lanceley, Galina Velikova, Eduardo Sabate, Jacobus Pfisterer, Mark S Carey, Philip Beale, Wendi Qian, Ann Marie Swart, Amit Oza, Tim Perren
Journal: The Lancet Oncology (2013)
Densely Ionizing Radiation Acts via the Microenvironment to Promote Aggressive <i>Trp53</i>-Null Mammary Carcinomas
Authors: Irineu Illa-Bochaca, Haoxu Ouyang, Jonathan Tang, Christopher Sebastiano, Jian-Hua Mao, Sylvain V. Costes, Sandra Demaria, Mary Helen Barcellos-Hoff
Journal: Cancer Research (2014)

Densely ionizing radiation, which is present in the space radiation environment and used in radiation oncology, has potentially greater carcinogenic effect compared with sparsely ionizing radiation that is prevalent on earth. Here, we used a radiation chimera in which mice were exposed to densely ionizing 350 MeV/amu Si-particles, γ-radiation, or sham-irradiated and transplanted 3 days later with syngeneic Trp53-null mammary fragments. Trp53-null tumors arising in mice irradiated with Si-particles had a shorter median time to appearance and grew faster once detected compared with those in sham-irradiated or γ-irradiated mice. Tumors were further classified by markers keratin 8/18 (K18, KRT18), keratin 14 (K14, KRT14) and estrogen receptor (ER, ESR1), and expression profiling. Most tumors arising in sham-irradiated hosts were comprised of both K18- and K14-positive cells (K14/18) while those tumors arising in irradiated hosts were mostly K18. Keratin staining was significantly associated with ER status: K14/18 tumors were predominantly ER-positive, whereas K18 tumors were predominantly ER-negative. Genes differentially expressed in K18 tumors compared with K14/18 tumor were associated with ERBB2 and KRAS, metastasis, and loss of E-cadherin. Consistent with this, K18 tumors tended to grow faster and be more metastatic than K14/18 tumors, however, K18 tumors in particle-irradiated mice grew significantly larger and were more metastatic compared with sham-irradiated mice. An expression profile that distinguished K18 tumors arising in particle-irradiated mice compared with sham-irradiated mice was enriched in mammary stem cell, stroma, and Notch signaling genes. These data suggest that carcinogenic effects of densely ionizing radiation are mediated by the microenvironment, which elicits more aggressive tumors compared with similar tumors arising in sham-irradiated hosts.
Hypoxia-Inducible Carbonic Anhydrase IX and XII Promote Tumor Cell Growth by Counteracting Acidosis through the Regulation of the Intracellular pH
Authors: Johanna Chiche, Karine Ilc, Julie Laferrière, Eric Trottier, Frédéric Dayan, Nathalie M. Mazure, M. Christiane Brahimi-Horn, Jacques Pouysségur
Journal: Cancer Research (2008)

Abstract Acidosis of the tumor microenvironment is typical of a malignant phenotype, particularly in hypoxic tumors. All cells express multiple isoforms of carbonic anhydrase (CA), enzymes catalyzing the reversible hydration of carbon dioxide into bicarbonate and protons. Tumor cells express membrane-bound CAIX and CAXII that are controlled via the hypoxia-inducible factor (HIF). Despite the recognition that tumor expression of HIF-1α and CAIX correlates with poor patient survival, the role of CAIX and CAXII in tumor growth is not fully resolved. To understand the advantage that tumor cells derive from expression of both CAIX and CAXII, we set up experiments to either force or invalidate the expression of these enzymes. In hypoxic LS174Tr tumor cells expressing either one or both CA isoforms, we show that (a) in response to a “CO2 load,” both CAs contribute to extracellular acidification and (b) both contribute to maintain a more alkaline resting intracellular pH (pHi), an action that preserves ATP levels and cell survival in a range of acidic outside pH (6.0–6.8) and low bicarbonate medium. In vivo experiments show that ca9 silencing alone leads to a 40% reduction in xenograft tumor volume with up-regulation of ca12 mRNA levels, whereas invalidation of both CAIX and CAXII gives an impressive 85% reduction. Thus, hypoxia-induced CAIX and CAXII are major tumor prosurvival pHi-regulating enzymes, and their combined targeting shows that they hold potential as anticancer targets. [Cancer Res 2009;69(1):358–68]
The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo
Authors: Jianuo Liu, Takashi Miwa, Brendan Hilliard, Youhai Chen, John D. Lambris, Andrew D. Wells, Wen-Chao Song
Journal: The Journal of Experimental Medicine (2005)

Decay-accelerating factor ([DAF] CD55) is a glycosylphosphatidylinositol-anchored membrane inhibitor of complement with broad clinical relevance. Here, we establish an additional and unexpected role for DAF in the suppression of adaptive immune responses in vivo. In both C57BL/6 and BALB/c mice, deficiency of the Daf1 gene, which encodes the murine homologue of human DAF, significantly enhanced T cell responses to active immunization. This phenotype was characterized by hypersecretion of interferon (IFN)-γ and interleukin (IL)-2, as well as down-regulation of the inhibitory cytokine IL-10 during antigen restimulation of lymphocytes in vitro. Compared with wild-type mice, Daf1−/− mice also displayed markedly exacerbated disease progression and pathology in a T cell–dependent experimental autoimmune encephalomyelitis (EAE) model. However, disabling the complement system in Daf1−/− mice normalized T cell secretion of IFN-γ and IL-2 and attenuated disease severity in the EAE model. These findings establish a critical link between complement and T cell immunity and have implications for the role of DAF and complement in organ transplantation, tumor evasion, and vaccine development.
Differences in kinematics and heart rate variability between winner and loser of various skilled levels during competitive golf putting tournament
Authors: J S Choi, H S Kim, K R Mun, D W Kang, M S Kang, Y H Bang, H S Oh, J H Yi, Y T Lim, G R Tack
Journal: British Journal of Sports Medicine (2010)

Putting is a crucial stroke to determine winning in golf. Putting is more delicate than any other strokes in golf. To keep better putting stroke, psychological factors as well as physical factors are important for golfers. The purpose of this study was to compare differences in kinematic and psychological variables between winner and loser of three skilled levels during competitive golf putting tournament. The participants consisted of 3 groups based on their skill levels: PG (8 professional golfers), RG (8 recreational golfers) and NG (8 novice golfers). Each group performed 8 tournaments by attempting 2.1 m putting from the hole. 3D motion analysis system with 6 high speed cameras and BIOPAC ECG module were used to acquire kinematic data and ECG. To compare differences between winner and loser for each group, time phase of putting stroke, smoothness by jerk cost function (JC), heart rate (HR), ratio of low and high frequency component (LF/HF) in heart rate variability and CSAI-2 scores (competitive state anxiety inventory 2) were used. There was a significant difference in back-swing phase time ratio between PG and other groups and in JC at the putter toe between NG and other groups. There was a significant difference in LF/HF and self-confidence score of CSAI-2 between winner and loser within PG. While PG and RG showed similar kinematic performance, they showed different LF/HF. The tonic states derived from cardiac activity indicated that a higher skilled level was associated with increased LF. Increased LF is associated with increased automaticity and decreased attention demands, which means that increased mental workload reduces LF. For PG, it may reveal that psychological factor is one of the important factors for the better performance during competition. Further studies are necessary to clarify psychological factors of putting by using different measurement techniques such as galvanic skin response.