tbuckley/cabot-search huggingface dataset:
Apoptosis in the course of granulomatous inflammation in pulmonary sarcoidosis
Authors: R Kunitake, K Kuwano, H Miyazaki, N Hagimoto, Y Nomoto, N Hara
Journal: European Respiratory Journal (1999)

Sarcoidosis is a chronic inflammatory disease of unknown aetiology characterized by the formation of non-necrotizing granulomas. The course of disease is usually self-limiting with the spontaneous resolution of granuloma. In the immune system, Fas antigen (Fas) and Fas ligand (FasL) are involved in the down regulation of immune reactions by inducing apoptosis. Therefore, it was hypothesized that the Fas/FasL pathway and apoptosis may be associated with the course of granulomatous inflammation in sarcoidosis. Terminal deoxynucleotidyl transferase-mediated biotin nick end-labelling (TUNEL) was performed to assess deoxyribonucleic acid strand breakages as a characteristic of apoptosis. Immunohistochemistry was also performed to detect Fas and FasL protein, and reverse transcriptase polymerase chain reaction (RT-PCR) and RT in situ PCR to detect FasL messenger ribonucleic acid (mRNA). Positive signals for TUNEL were detected in epithelioid histiocytes and lymphocytes within granulomas and in bronchoalveolar lavage (BAL) lymphocytes from patients with sarcoidosis. Positive signals for Fas were also detected in these cells. FasL mRNA was expressed in BAL lymphocytes from 15 of 20 patients with sarcoidosis, but from only one of 10 patients with normal lung parenchyma. FasL protein was expressed in lymphocytes surrounding and within the granuloma. There was a significant correlation between the result of TUNEL and clinical course in patients with sarcoidosis. Apoptosis in epithelioid histiocytes and inflammatory cells seems to participate in the course of granulomatous inflammation. Further studies are needed to determine the role of Fas, FasL and other regulatory factors in apoptosis in the granulomatous inflammation in pulmonary sarcoidosis.
EGFR Tyrosine Kinase Inhibitors in Lung Cancer: An Evolving Story
Authors: Lecia V. Sequist, Thomas J. Lynch
Journal: Annual Review of Medicine (2007)

Drugs that target the epidermal growth factor receptor (EGFR) have had a major impact on the treatment of non-small cell lung cancer (NSCLC). The use of these drugs has also motivated pivotal advances in the understanding of the molecular biology of NSCLC, including the discovery that mutations in EGFR are associated with dramatic and sustained responses to anti-EGFR treatments. This review summarizes the clinical development of EGFR tyrosine kinase inhibitors, the discovery of molecular predictors of response, and the future directions for research in the field.
SUCCESSFUL BEHAVIORAL INTERVENTIONS TO PREVENT CANCER: The Example of Skin Cancer
Authors: A. Baum, L. Cohen
Journal: Annual Review of Public Health (1998)

Important behavioral sources of risk for cancer have been identified and programs to reduce this risk have been initiated. The most heavily studied behavioral risk is tobacco use, but considerable attention has also gone to prevention of skin cancer by modifying sun exposure. Research has shown a strong link between sun exposure and skin cancer, and opportunities to prevent this cancer by changing behavior should be effective. Unlike unmodifiable sources of risk, sun exposure should be modifiable through behavioral intervention. This review considers research in this expanding area, concentrating on predictors of sun protective behaviors, modification of sun exposure, and surveillance for early signs of cancer. The elements of behavior change programs that contribute to successful intervention as well as barriers to successful behavior change and future directions for this effort are considered.
Digestive system cancer among persons subjected to occupational inhalation of asbestos particles: a literature review with emphasis on dose response
Authors: Marvin A. Schneiderman
Journal: Environmental Health Perspectives (1974)

Human data show a dose-response relationship between industrial exposure to asbestos and later development of cancer of the bronchus and lung and of cancer of the digestive tract. The data do not provide much evidence for a threshold or for the existence of a clearly "safe" level of exposure. Good dose-response data, with quantitative estimates of dose are uncommon; however, in all the literature reviewed only one paper did not support the conclusion that increased exposure to inhaled asbestos particles leads to increased digestive system cancer.
Association Between Travel Distance and Metastatic Disease at Diagnosis Among Patients With Colon Cancer
Authors: Nader N. Massarweh, Yi-Ju Chiang, Yan Xing, George J. Chang, Alex B. Haynes, Y. Nancy You, Barry W. Feig, Janice N. Cormier
Journal: Journal of Clinical Oncology (2014)

Health care access and advanced cancer stage are associated with oncologic outcomes for numerous common cancers. However, the impact of patient travel distance to health care on stage at diagnosis has not been well characterized.This study used a historical cohort of patients with colon cancer in the National Cancer Data Base from 2003 through 2010. The primary outcome, stage at diagnosis, was evaluated using hierarchical regression modeling. A secondary outcome was time to receipt of initial therapy that was evaluated using Cox shared frailty modeling.Among 296,474 patients with colon cancer (mean age, 68 ± 13.6 years; 47.6% male; 78.5% white), 3.9% traveled ≥ 50 miles to the diagnosing facility. Fewer black patients, patients with higher income, and patients with lower education traveled longer distances (trend test P < .001 for all). Patients traveling ≥ 50 miles were more likely to present with metastatic disease compared with those traveling less than 12.5 miles (odds ratio [OR], 1.18; 95% CI, 1.12 to 1.24) or 12.5 to 49.9 miles (OR, 1.18; 95% CI, 1.12 to 1.24). In sensitivity analyses, the association was robust to alternate methods of modeling travel distance (quintile stratification or continuous). Travel distance ≥ 50 miles was also associated with a higher likelihood of earlier initiation of therapy compared with travel distance of less than 12.5 miles (hazard ratio [HR], 1.10; 95% CI, 1.08 to 1.13) or 12.5 to 49.9 miles (HR, 1.11; 95% CI, 1.08 to 1.13).Advanced colon cancer stage at diagnosis is associated with patient travel distance to health care, which may be a barrier to early cancer screening. Health care reform efforts designed to address only insurance coverage may not mitigate disparities based on difficulties accessing cancer care.
The Utility of Childhood Asthma Control Test and its Relationship with Control Measures and with the Decisions Made by Asthma Specialist
Authors: B.E. Sekerel, O. Keskin, N. Uzuner, M. Yazicioglu, M. Kilic, H. Artac, S. Ozmen, D. Can, D. Zeyrek, H. Cokugras, O. Soyer, N. Sapan, M. Aydogan, S. Kuyucu, A. Inal, F. Gurkan, F. Orhan, O. Yilmaz, A. Bingol Boz, F. Tahan, O. Cevit
Journal: Journal of Allergy and Clinical Immunology (2010)
Triazolothienopyrimidine Inhibitors of Urea Transporter UT-B Reduce Urine Concentration
Authors: Chenjuan Yao, Marc O. Anderson, Jicheng Zhang, Baoxue Yang, Puay-Wah Phuan, A.S. Verkman
Journal: Journal of the American Society of Nephrology (2012)

Urea transport (UT) proteins facilitate the concentration of urine by the kidney, suggesting that inhibition of these proteins could have therapeutic use as a diuretic strategy. We screened 100,000 compounds for UT-B inhibition using an optical assay based on the hypotonic lysis of acetamide-loaded mouse erythrocytes. We identified a class of triazolothienopyrimidine UT-B inhibitors; the most potent compound, UTB(inh)-14, fully and reversibly inhibited urea transport with IC(50) values of 10 nM and 25 nM for human and mouse UT-B, respectively. UTB(inh)-14 competed with urea binding at an intracellular site on the UT-B protein. UTB(inh)-14 exhibited low toxicity and high selectivity for UT-B over UT-A isoforms. After intraperitoneal administration of UTB(inh)-14 in mice to achieve predicted therapeutic concentrations in the kidney, urine osmolality after administration of 1-deamino-8-D-arginine-vasopressin was approximately 700 mosm/kg H(2)O lower in UTB(inh)-14-treated mice than vehicle-treated mice. UTB(inh)-14 also increased urine output and reduced urine osmolality in mice given free access to water. UTB(inh)-14 did not reduce urine osmolality in UT-B knockout mice. In summary, these data provide proof of concept for the potential utility of UT inhibitors to reduce urinary concentration in high-vasopressin, fluid-retaining conditions. The diuretic mechanism of UT inhibitors may complement the action of conventional diuretics, which target sodium transport.
Circadian rhythm of serum cytidine deaminase in patients with rheumatoid arthritis during rest and exercise.
Authors: P W Thompson, I T James, S Wheatcroft, R Pownall, C G Barnes
Journal: Annals of the Rheumatic Diseases (1989)

Circadian rhythm of serum cytidine deaminase and C reactive protein was assessed in 11 inpatients with rheumatoid arthritis who were crossed between 24 hours of bed rest and 24 hours of normal ward activity. Blood was taken at six hourly intervals and the results analysed by fitting sine waves with an assumed period of 24 hours to the measured concentrations. Cytidine deaminase after activity, but not at rest, showed circadian variation, with a 24 hour mean level of 17.4 units (normal 3-13 units) and an amplitude of 1.1 units. The circadian variation, defined as the curve's peak to trough difference as a percentage of the 24 hour mean, was 12.3% and occurred at 1208 hours. C reactive protein showed no significant circadian rhythm, in keeping with published findings. The timing of the peak in serum cytidine deaminase concentrations after a period of morning physiotherapy, but not during the bedrest morning, suggests that exercise accounts for the circadian rhythm, probably by increasing the lymphatic clearance from inflamed joints.
Prostaglandin D<sub>2</sub>inhibits fibroblast migration
Authors: T. Kohyama, X.D. Liu, F.Q. Wen, H.J. Kim, H. Takizawa, S.I. Rennard
Journal: European Respiratory Journal (2002)

Fibroblasts play an important role in the repair and remodelling processes following injury. Prostaglandin D 2 (PGD 2 ) is a potent mediator in inflammatory processes. In this study, the effect of the PGD 2 on human foetal lung fibroblasts (HFL‐1) chemotaxis induced by human plasma fibronectin (HFn) was investigated using the blindwell chamber technique. PGD 2 inhibited HFL‐1 chemotaxis to HFn (20 µg·mL −1 ) by 20.8±3.8% (p&lt;0.05). Checkerboard analysis of HFn-directed migration confirmed that PGD 2 inhibited both chemotaxis and chemokinesis. The effect of PGD 2 was concentration-dependent and the inhibitory effect diminished with time. The PGD 2 receptor (DP) agonist BW245C (500 nM) had a similar effect, inhibiting chemotaxis to 39.4±6.3%. The inhibitory effects of both PGD 2 and BW245C on HFL‐1 chemotaxis were blocked by the DP receptor antagonist AH6809 (2 µM). The inhibitory effect of PGD 2 on fibroblast chemotaxis was also blocked by the cyclic adenosine monophosphate (cAMP)‐dependent protein kinase (PKA) inhibitor, KT5720, suggesting a DP receptor-initiated, cAMP‐dependent effect mediated by PKA. Prostaglandin D 2 appears to inhibit fibroblast chemotaxis, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of the wound healing response following injury in asthma patients.
On the causes of lung hyperinflation during bronchoconstriction
Authors: R Pellegrino, V Brusasco
Journal: European Respiratory Journal (1997)

Airway obstruction in asthma and chronic obstructive pulmonary disease (COPD) is often associated with lung hyperinflation. In this review, we examine the mechanisms that may cause functional residual capacity (FRC), residual volume (RV) and total lung capacity (TLC) to increase during acute and chronic airway obstruction. Normally, FRC at rest is determined by the static characteristics of the lung and chest wall. When airways narrow, FRC may be also be determined by dynamic factors. There are data suggesting that expiratory flow limitation during tidal breathing represents the starting trigger for FRC to increase, in order to allow breathing at higher flows. Indeed, the increase in FRC during induced bronchoconstriction in asthma is closely associated with the occurrence of flow limitation, i.e. the achievement of maximum flow during tidal breathing. Conversely, the decrease in FRC following bronchodilatation in COPD is closely associated with flow limitation disappearing or occurring at lower lung volumes. In normal young people, RV is determined by the static characteristics of the chest wall. During bronchoconstriction RV may also be determined by dynamic factors; therefore, changes in flow or airway calibre at low lung volumes may modulate RV during bronchoconstriction. During acutely induced bronchoconstriction, RV achieved with an expiration from TLC is less than with an expiration from tidal breathing, and this effect appears to be linked to the bronchodilator effect of the deep inhalation. The reasons for the increase in TLC during airway narrowing are not clear, but the duration of the bronchoconstriction by itself may play a role.
National EQ-5D tariffs and quality-adjusted life-year estimation: comparison of UK, US and Danish utilities in south Swedish rheumatoid arthritis patients
Authors: J. A. Karlsson, J.-A. Nilsson, M. Neovius, L.-E. Kristensen, A. Gulfe, T. Saxne, P. Geborek
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To study how the choice of national EQ-5D tariff may affect utility and incremental quality-adjusted life-year (QALY) estimates. <h3>Methods</h3> South Swedish rheumatoid arthritis patients in an observational study, starting and continuing anti-tumour necrosis factor (TNF) monotherapy (n=54) or anti-TNF plus methotrexate (n=215) for 1 year during May 2002 to April 2009, were included. EQ-5D questionnaires were completed at baseline, 3, 6 and 12 months. Utilities and accumulated QALY were compared using the UK, US and Danish EQ-5D tariffs. Utilities for all 243 possible EQ-5D health states were also compared. <h3>Results</h3> US utilities were generally higher than UK, with Danish falling in between. A substantial 1-year mean utility improvement was seen in both study groups using all tariffs (UK 0.28 vs 0.29; US 0.18 vs 0.19; Danish 0.20 vs 0.22). Adjusting for baseline differences between groups, the incremental QALY gain of combined treatment was 0.09 using the UK tariff, while 0.06 according to both US and Danish tariffs. Inter-tariff disagreement in utility and accumulated QALY varied irregularly across the range of utilities. <h3>Conclusions</h3> Applying different national EQ-5D tariffs to the same data may result in substantially different incremental QALY estimates, crucial knowledge when interpreting cost-utility analyses. Studies using different tariffs cannot be directly compared.
p53 Negatively Regulates the Hepatoma Growth Factor HDGF
Authors: Yasushi Sasaki, Hideaki Negishi, Masashi Idogawa, Ikuko Yokota, Ryota Koyama, Masanobu Kusano, Hiromu Suzuki, Masahiro Fujita, Reo Maruyama, Minoru Toyota, Tsuyoshi Saito, Takashi Tokino
Journal: Cancer Research (2011)

Hepatoma-derived growth factor (HDGF) is a secreted heparin-binding growth factor that has been implicated in cancer development and progression. Here, we report that HDGF is a critical target for transcriptional repression by the tumor suppressor p53. Endogenous HDGF expression was decreased in cancer cells with introduction of wild-type p53, which also downregulated HDGF expression after DNA damage. In support of the likelihood that HDGF is a critical driver of cancer cell growth, addition of neutralizing HDGF antibodies to culture media was sufficient to block cell growth, migration, and invasion. Similarly, these effects were elicited by conditioned culture medium from p53-expressing cells, and they could be reversed by the addition of recombinant human HDGF. Interestingly, we found that HDGF was overexpressed also in primary gastric, breast, and lung cancer tissues harboring mutant p53 genes. Mechanistic investigations revealed that p53 repressed HDGF transcription by altering HDAC-dependent chromatin remodeling. Taken together, our results reveal a new pathway in which loss of p53 function contributes to the aggressive pathobiological potential of human cancers by elevating HDGF expression.
Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction
Authors: Maria Teresa La Rovere, J Thomas Bigger, Frank I Marcus, Andrea Mortara, Peter J Schwartz
Journal: The Lancet (1998)

Experimental evidence suggests that autonomic markers such as heart-rate variability and baroreflex sensitivity (BRS) may contribute to postinfarction risk stratification. There are clinical data to support this concept for heart-rate variability. The main objective of the ATRAMI study was to provide prospective data on the additional and independent prognostic value for cardiac mortality of heart-rate variability and BRS in patients after myocardial infarction in whom left-ventricular ejection fraction (LVEF) and ventricular arrhythmias were known.This multicentre international prospective study enrolled 1284 patients with a recent (<28 days) myocardial infarction. 24 h Holter recording was done to quantify heart-rate variability (measured as standard deviation of normal to normal RR intervals [SDNN]) and ventricular arrhythmias. BRS was calculated from measurement of the rate-pressure response to intravenous phenylephrine.During 21 (SD 8) months of follow-up, the primary endpoint, cardiac mortality, included 44 cardiac deaths and five non-fatal cardiac arrests. Low values of either heart-rate variability (SDNN <70 ms) or BRS (<3.0 ms per mm Hg) carried a significant multivariate risk of cardiac mortality (3.2 [95% CI 1.42-7.36] and 2.8 [1.24-6.16], respectively). The association of low SDNN and BRS further increased risk; the 2-year mortality was 17% when both were below the cut-offs and 2% (p<0.0001) when both were well preserved (SDNN >105 ms, BRS >6.1 ms per mm Hg). The association of low SDNN or BRS with LVEF below 35% carried a relative risk of 6.7 (3.1-14.6) or 8.7 (4.3-17.6), respectively, compared with patients with LVEF above 35% and less compromised SDNN (> or = 70 ms) and BRS (> or = 3 ms per mm Hg).ATRAMI provides clinical evidence that after myocardial infarction the analysis of vagal reflexes has significant prognostic value independently of LVEF and of ventricular arrhythmias and that it significantly adds to the prognostic value of heart-rate variability.
Compartmentalization of Mammalian Folate-Mediated One-Carbon Metabolism
Authors: Anne S. Tibbetts, Dean R. Appling
Journal: Annual Review of Nutrition (2010)

The recognition that mitochondria participate in folate-mediated one-carbon metabolism grew out of pioneering work beginning in the 1950s from the laboratories of D.M. Greenberg, C.G. Mackenzie, and G. Kikuchi. These studies revealed mitochondria as the site of oxidation of one-carbon donors such as serine, glycine, sarcosine, and dimethylglycine. Subsequent work from these laboratories and others demonstrated the participation of folate coenzymes and folate-dependent enzymes in these mitochondrial processes. Biochemical and molecular genetic approaches in the 1980s and 1990s identified many of the enzymes involved and revealed an interdependence of cytoplasmic and mitochondrial one-carbon metabolism. These studies led to the development of a model of eukaryotic one-carbon metabolism that comprises parallel cytosolic and mitochondrial pathways, connected by one-carbon donors such as serine, glycine, and formate. Sequencing of the human and other mammalian genomes has facilitated identification of the enzymes that participate in this intercompartmental one-carbon metabolism, and animal models are beginning to clarify the roles of the cytoplasmic and mitochondrial isozymes of these enzymes. Identifying the mitochondrial transporters for the one-carbon donors and elucidating how flux through these pathways is controlled are two areas ripe for exploration.
Elongation factor-1 alpha occurs as two copies in bees: implications for phylogenetic analysis of EF-1 alpha sequences in insects
Authors: B. N. Danforth, S. Ji
Journal: Molecular Biology and Evolution (1998)

We report the complete sequence of a paralogous copy of elongation factor-1 alpha (EF-1 alpha) in the honeybee, Apis mellifera (Hymenoptera: Apidae). This copy differs from a previously described copy in the positions of five introns and in 25% of the nucleotide sites in the coding regions. The existence of two paralogous copies of EF-1 alpha in Drosophila and Apis suggests that two copies of EF-1 alpha may be widespread in the holometabolous insect orders. To distinguish between a single, ancient gene duplication and parallel, independent fly and bee gene duplications, we performed a phylogenetic analysis of hexapod EF-1 alpha sequences. Unweighted parsimony analysis of nucleotide sequences suggests an ancient gene duplication event, whereas weighted parsimony analysis of nucleotides and unweighted parsimony analysis of amino acids suggests the contrary: that EF-1 alpha underwent parallel gene duplications in the Diptera and the Hymenoptera. The hypothesis of parallel gene duplication is supported both by congruence among nucleotide and amino acid data sets and by topology-dependent permutation tail probability (T-PTP) tests. The resulting tree topologies are also congruent with current views on the relationships among the holometabolous orders included in this study (Diptera, Hymenoptera, and Lepidoptera). More sequences, from diverse orders of holometabolous insects, will be needed to more accurately assess the historical patterns of gene duplication in EF-1 alpha.
The complexity of bladder cancer: long noncoding RNAs are on the stage
Authors: Quanan Zhang, Mo Su, Guangming Lu, Jiangdong Wang
Journal: Molecular Cancer (2013)

Abstract The mammalian genome encodes thousands of long noncoding RNAs (lncRNAs) and it is increasingly clear that lncRNAs are key regulators of cellular function and development. Gain and/or loss of function studies in cell culture indicate that lncRNAs can regulate gene transcription indirectly through the targeting and recruitment of chromatin-modifying complexes as well as directly at the transcriptional or posttranscriptional levels. LncRNA biology is attracting great attention in cancer research because dysregulated lncRNAs occur in a variety of cancers, placing lncRNAs on the stage of cancer genome research. We briefly describe the latest lncRNA biology and discuss the oncogenic lncRNAs involved in core pathways in bladder cancer and the application of lncRNAs to its diagnosis and targeted treatment. LncRNAs are becoming essential components of the gene regulatory circuitry in the complexity of bladder cancer.
Levofloxacin vs. ciprofloxacin plus phenethicillin for the prevention of bacterial infections in patients with haematological malignancies
Authors: G.J. Timmers, A.M. Simoons-Smit, M.E. Leidekker, J.J.W.M. Janssen, C.M.J.E. Vandenbroucke-Grauls, P.C. Huijgens
Journal: Clinical Microbiology and Infection (2007)