tbuckley/cabot-search huggingface dataset:
Towards the next stage of novel biomarker discussion in COPD: Tekizai-Tekisho
Authors: T. Oga, K. Chin, M. Mishima
Journal: European Respiratory Journal (2014)

Forced expiratory volume in 1 s (FEV1) as a degree of airflow limit2ation has traditionally been regarded as a crucial predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). However, the situation has changed over the past 10 years. Various systemic clinical outcome measurements, such as exercise capacity, dyspnoea, health status, etc ., have been found to be associated with mortality [1, 2]. Thus, combined multidimensional disease severity grading protocols have been proposed. To date, the BODE index (body mass index, dyspnoea, exercise capacity and airflow limitation) has led the field as a predictor of disease [3].

Being liberated from the “FEV1 supremacy”, COPD has been increasingly recognised as a heterogeneous disease. “Systemic COPD” is one of phenotypes associated with elevated markers of systemic inflammation and a high prevalence of comorbidities. The systemic inflammatory phenotype yields poor clinical outcomes with increased mortality and exacerbation frequency [4]. Systemic inflammation in COPD cannot be explained simply by a “spill-over” phenomenon of inflammatory mediators from the lungs [5]. Other factors such as bronchial colonisation, obesity, hypoxia and comorbidities are involved. Therefore, a single marker does not seem to be sufficient in assessing systemic effects of COPD, and a combination of multiple markers may have advantages.

Given our recent understanding of this situation, the BODE index may not sufficiently represent factors related to such systemic inflammation. Cross-sectionally, associations between the BODE index and systemic inflammatory biomarkers were not strong [6]. Similarly, from the longitudinal point of view, some serum biomarkers have an additive predictive value of mortality with the BODE index [7, 8]. In addition, regarding comorbidities, …
Prostate-Specific Antigen Velocity for Early Detection of Prostate Cancer: Result from a Large, Representative, Population-based Cohort
Authors: Andrew J. Vickers, Tineke Wolters, Caroline J. Savage, Angel M. Cronin, M. Frank O’Brien, Kim Pettersson, Monique J. Roobol, Gunnar Aus, Peter T. Scardino, Jonas Hugosson, Fritz H. Schröder, Hans Lilja
Journal: European Urology (2009)
Reply to D. Serraino et al
Authors: Ann H. Partridge, Shari Gelber, Richard Gelber
Journal: Journal of Clinical Oncology (2013)

In their article, Partridge et al 1 concluded that "age was not strongly associated with risk of early recurrence or prediction of benefit from trastuzumab therapy." 1(p2692) In our opinion, such conclusive statement is weakly supported by the data shown in tables.In both the observation and the trastuzumab groups, the authors do not provide detailed data on the age distribution of studied women.This lack of information is, in our opinion, of particular importance with regard to the women aged over 40 years.With a reported median age of 52 years, 670/671 older women in the observation group and 669 older women in the trastuzumab group should be aged 53 years or older.There seems to be enough statistical power to expand the older than 40 years group in the Cox model (eg, 41 to 59, 60-69, 70 years or older) for comparison with women aged 40 years or younger (ie, 357 in the observation group and 365 in the trastuzumab group).We would be interested in seeing whether the findings reported by Partrdige et al will be homogenous across age strata in older women.
Selective control of type I IFN induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation
Authors: Kazuhito Gotoh, Yoshihiko Tanaka, Akihiko Nishikimi, Risa Nakamura, Hisakata Yamada, Naoyoshi Maeda, Takahiro Ishikawa, Katsuaki Hoshino, Takehito Uruno, Qinhong Cao, Sadayuki Higashi, Yasushi Kawaguchi, Munechika Enjoji, Ryoichi Takayanagi, Tsuneyasu Kaisho, Yasunobu Yoshikai, Yoshinori Fukui
Journal: The Journal of Experimental Medicine (2010)

Plasmacytoid dendritic cells (pDCs) play a key role in antiviral immunity, but also contribute to the pathogenesis of certain autoimmune diseases, by producing large amounts of type I IFNs. Although activation of pDCs is triggered by engagement of nucleotide-sensing toll-like receptors (TLR) 7 and 9, type I IFN induction additionally requires IκB kinase (IKK) α–dependent activation of IFN regulatory factor (IRF) 7. However, the signaling pathway mediating IKK-α activation is poorly defined. We show that DOCK2, an atypical Rac activator, is essential for TLR7- and TLR9-mediated IFN-α induction in pDCs. We found that the exposure of pDCs to nucleic acid ligands induces Rac activation through a TLR-independent and DOCK2-dependent mechanism. Although this Rac activation was dispensable for induction of inflammatory cytokines, phosphorylation of IKK-α and nuclear translocation of IRF-7 were impaired in Dock2-deficient pDCs, resulting in selective loss of IFN-α induction. Similar results were obtained when a dominant-negative Rac mutant was expressed in wild-type pDCs. Thus, the DOCK2–Rac signaling pathway acts in parallel with TLR engagement to control IKK-α activation for type I IFN induction. Owing to its hematopoietic cell-specific expression, DOCK2 may serve as a therapeutic target for type I IFN–related autoimmune diseases.
Overexpressed-eIF3I interacted and activated oncogenic Akt1 is a theranostic target in human hepatocellular carcinoma
Authors: Yi-Wei Wang, Kuen-Tyng Lin, Shu-Chuan Chen, De-Leung Gu, Chian-Feng Chen, Pang-Hsien Tu, Yuh-Shan Jou
Journal: Hepatology (2013)

Eukaryotic translation initiation factor 3 subunit I (eIF3I) with transforming capability is often overexpressed in human hepatocellular carcinoma (HCC) but its oncogenic mechanisms remain unknown. We demonstrate that eIF3I is overexpressed in various cancers along with activated Akt1 phosphorylation and kinase activity in an eIF3I dose-dependent manner. A novel eIF3I and Akt1 protein interaction was identified in HCC cell lines and tissues and was required for eIF3I-mediated activation of Akt1 signaling. Expression of either antisense eIF3I or dominant negative Akt1 mutant suppressed eIF3I-mediated Akt1 oncogenic signaling and various other tumorigenic effects. Oncogenic domain mapping of the eIF3I and Akt1 interaction suggested that the C-terminal eIF3I interacted with the Akt1 kinase domain and conferred the majority of oncogenic functions. In addition, eIF3I interaction with Akt1 prevented PP2A dephosphorylation of Akt1 and resulted in constitutively active Akt1 oncogenic signaling. Importantly, concordant expression of endogenous eIF3I and phospho-Akt1 was detected in HCC cell lines and tissues. Treatment of eIF3I overexpressing HCC cells with the Akt1 specific inhibitor API-2 suppressed eIF3I-mediated tumorigenesis in vitro and in vivo.We describe a constitutive Akt1 oncogenic mechanism resulting from interaction of overexpressed eIF3I with Akt1 that prevents PP2A-mediated dephosphorylation. Overexpression of eIF3I in HCC is oncogenic and is a surrogate marker and therapeutic target for treatment with Akt1 inhibitors.
Growth Curve of a Murine Leukemia Virus in Mice
Authors: Frank J. Rauscher, Barbara V. Allen
Journal: JNCI Journal of the National Cancer Institute (1964)

The growth curves of a murine leukemogenic virus in plasma and spleen of BALB/c mice were similar to those of many non-neoplastic animal viruses. Virus disappeared rapidly after inoculation, and within 1 day little or no infective virus could be demonstrated. This was followed by a stationary or eclipse phase of approximately 4 days during which virus could not be recovered from the plasma or spleen. Beginning on the 5th day after inoculation, relatively large amounts of virus were present in both plasma and spleen and increased progressively until reaching a high plateau between the 7th and 14th days. There was no significant difference between the time required for demonstrable virus to appear in plasma or spleen. The spleen was the first tissue to show histologic evidence of disease. The presence of large amounts of virus in plasma before the development of leukemia is discussed in relation to the importance of non-neoplastic cells in the early synthesis of virus.
Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers
Authors: Francis KL Chan, Joseph JY Sung, SC Sydney Chung, KF To, MY Yung, Vincent KS Leung, YT Lee, Cynthia SY Chan, Edmund KM Li, Jean Woo
Journal: The Lancet (1997)
Mechanisms of the occasional self
Authors: Don M. Tucker
Journal: Behavioral and Brain Sciences (2005)

Considered in relation to the component brain systems of appraisal-emotion interactions, dynamical systems theory blurs the divisions that seem obvious in a psychological analysis, such as between arousal, emotion, and appraisal. At the same time, the component brain mechanisms can themselves be seen to be incomplete as units of analysis, making sense only in the context of the whole organism.
REMOVAL OF EXTRAMEDULLARY TUMOUR OF CERVICAL CORD: RECOVERY: (AREA OF SUPPLY OF EIGHTH CERVICAL AND FIRST DORSAL POSTERIOR ROOTS.)
Authors: J. M. Clarke
Journal: BMJ (1912)

CERVICAL CORD.[ -TIfL raT 1'75 In disseminated sclerosis, where the symptoms are particularly variable on account of the sclerosed areas b3ing so inconstant in their distribution, the patient's leCgs are weak and spastic with all the tendon-reflexes exaggerated, while his (or her) arms, also weak, may be paraesthetic.More striking than this, however, and more important in the diagnosis, are its three cardinal symptoms, tremor, nystagmus, and staccato speech.By these it may be known, althouglh in the earlier stages, before these three have fully developed, a hysterical counterfeit may lead us astray.Compression of the cord, the result usually of caries of the spine, an aneurysm or a secondary growth, produces twofold symptoms-those of spinal root irritation followed by root paralysis, and those of a transverse lesion of the cord itself.Apart from these, however, we may expect a third set due to whatever is causing the compression.If this last group is not to be found, we are then thrown back on the possibility of some primary new growth inside the spinal canal, or a patch of chronically thickened meninges; in either case, the site of the pressure is identified by the distribution of the symptoms.The distinction between the two, however, may be a matter of difficulty.Perhaps the most suggestive differences are that in chronic meningitis the course is slower and that the pain, even from the beginning, is bilateral and spreads over a wider area.Moreover, the meningitis may improve witho-ut surgical treatment.
Multimeric forms of CD40 ligand (CD40L), 4-1BB ligand (4-1BBL), OX40 ligand (OX40L), CD27L/CD70, and other TNFSFs as tools for adoptive cell therapy
Authors: Richard S Kornbluth
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts The TNF SuperFamily (TNFSF) of ligands include 19 molecules some of which play key roles in the immune system. All of these ligands are produced as trimeric Type II membrane molecules that can be released from the cell surface as single trimers. However, more than a decade of
Nitric oxide contributes to the regulation of vasomotor tone but does not modulate O2-consumption in exercising swine
Authors: D Duncker
Journal: Cardiovascular Research (2000)

Objective: The role of nitric oxide (NO) in the regulation of vasomotor tone and tissue O2-consumption is incompletely understood. We therefore determined the contribution of endogenous NO to regulation of systemic, pulmonary and coronary vasomotor tone and myocardial (MVo2) and whole body (BVo2) O2-consumption in exercising swine. Methods and results: Exercise (1–5 km/h) up to 85% of maximum heart rate in 11 swine produced a 4-fold increase in BVo2, which was accommodated for by 2-fold increases in both cardiac output (CO) and body O2-extraction. The NO synthase inhibitor Nω-nitro-l-arginine (NLA, 20 mg/kg, i.v.) increased mean aortic pressure by 30 mmHg both at rest and during exercise, due to a decrease in systemic vascular conductance from 37±2 to 22±1 ml/min mmHg−1 at rest and from 88±3 to 60±3 ml/min mmHg−1 at 5 km/h (all P≤0.05 versus control). NLA produced vasoconstriction at rest and at 5 km/h in virtually all regional beds but did not affect the exercise-induced redistribution of CO. NLA increased mean pulmonary artery pressure from 15±1 to 21±1 mmHg at rest and from 30±2 to 40±2 mmHg at 5 km/h, due to a decrease in pulmonary vascular conductance (all P≤0.05). BVo2 remained unchanged and consequently the decrease in CO resulted in a compensatory increase in O2-extraction. NLA in a dose of 40 mg/kg produced similar responses. NLA had no significant effect on myocardial O2-demand or MVo2 either at rest or during exercise, but decreased coronary vascular conductance which resulted in a decrease in coronary venous Po2 from 24.5±1.1 to 21.9±0.8 mmHg at rest and from 23.5±0.5 to 21.0±0.6 mmHg at 5 km/h (all P≤0.05). Conclusions: Endogenous NO dilates the systemic, pulmonary and coronary vascular bed, but does not modify MVo2 or BVo2 in swine at rest and during exercise.
Clonal Architecture of Secondary Acute Myeloid Leukemia
Authors: Matthew J. Walter, Dong Shen, Li Ding, Jin Shao, Daniel C. Koboldt, Ken Chen, David E. Larson, Michael D. McLellan, David Dooling, Rachel Abbott, Robert Fulton, Vincent Magrini, Heather Schmidt, Joelle Kalicki-Veizer, Michelle O'Laughlin, Xian Fan, Marcus Grillot, Sarah Witowski, Sharon Heath, John L. Frater, William Eades, Michael Tomasson, Peter Westervelt, John F. DiPersio, Daniel C. Link, Elaine R. Mardis, Timothy J. Ley, Richard K. Wilson, Timothy A. Graubert
Journal: New England Journal of Medicine (2012)

The myelodysplastic syndromes are a group of hematologic disorders that often evolve into secondary acute myeloid leukemia (AML). The genetic changes that underlie progression from the myelodysplastic syndromes to secondary AML are not well understood.
Prevention of Hepatocellular Carcinoma Development Associated with Chronic Hepatitis by Anti-Fas Ligand Antibody Therapy
Authors: Yasunari Nakamoto, Shuichi Kaneko, Hong Fan, Takashi Momoi, Hiroko Tsutsui, Kenji Nakanishi, Kenichi Kobayashi, Takashi Suda
Journal: The Journal of Experimental Medicine (2002)

A persistent immune response to hepatitis viruses is a well-recognized risk factor for hepatocellular carcinoma. However, the molecular and cellular basis for the procarcinogenic potential of the immune response is not well defined. Here, using a unique animal model of chronic hepatitis that induces hepatocellular carcinogenesis, we demonstrate that neutralization of the activity of Fas ligand prevented hepatocyte apoptosis, proliferation, liver inflammation, and the eventual development of hepatocellular carcinoma. The results indicate that Fas ligand is involved not only in direct hepatocyte killing but also in the process of inflammation and hepatocellular carcinogenesis in chronic hepatitis. This is the first demonstration that amelioration of chronic inflammation by some treatment actually caused reduction of cancer development.
Autophagy regulates TNFα-mediated joint destruction in experimental arthritis
Authors: Neng-Yu Lin, Christian Beyer, Andreas Gießl, Trayana Kireva, Carina Scholtysek, Stefan Uderhardt, Luis Enrique Munoz, Clara Dees, Alfiya Distler, Stefan Wirtz, Gerhard Krönke, Brian Spencer, Oliver Distler, Georg Schett, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> Autophagy is a homeostatic process to recycle dispensable and damaged cell organelles. Dysregulation of autophagic pathways has recently been implicated in the pathogenesis of various diseases. Here, we investigated the role of autophagy during joint destruction in arthritis. <h3>Methods</h3> Autophagy in osteoclasts was analysed in vitro and ex vivo by transmission electron microscopy, Western blotting and immunohistochemistry for Beclin1 and Atg7. Small molecule inhibitors, LysMCre-mediated knockout of Atg7 and lentiviral overexpression of Beclin1 were used to modulate autophagy in vitro and in vivo. Osteoclast differentiation markers were quantified by real-time PCR. The extent of bone and cartilage destruction was analysed in human tumour necrosis factor α transgenic (hTNFα tg) mice after adoptive transfer with myeloid specific Atg7-deficient bone marrow. <h3>Results</h3> Autophagy was activated in osteoclasts of human rheumatoid arthritis (RA) showing increased expression of Beclin1 and Atg7. TNFα potently induced the expression of autophagy-related genes and activated autophagy in vitro and in vivo. Activation of autophagy by overexpression of Beclin1-induced osteoclastogenesis and enhanced the resorptive capacity of cultured osteoclasts, whereas pharmacologic or genetic inactivation of autophagy prevented osteoclast differentiation. Arthritic hTNFα tg mice transplanted with Atg7<sup>fl/fl</sup>×LysMCre<sup>+</sup> bone marrow cells (BMC) showed reduced numbers of osteoclasts and were protected from TNFα-induced bone erosion, proteoglycan loss and chondrocyte death. <h3>Conclusions</h3> These findings demonstrate that autophagy is activated in RA in a TNFα-dependent manner and regulates osteoclast differentiation and bone resorption. We thus provide evidence for a central role of autophagy in joint destruction in RA.
Recruitment and Activation of Natural Killer Cells<i>In vitro</i>by a Human Dendritic Cell Vaccine
Authors: Karin Gustafsson, Madeleine Ingelsten, Linda Bergqvist, Jenny Nyström, Bengt Andersson, Alex Karlsson-Parra
Journal: Cancer Research (2008)

Abstract Recruitment of circulating natural killer (NK) cells into inflamed lymph nodes is known to provide a potent, IFN-γ–dependent boost for Th1-polarized immune responses in mouse models. Such NK cell recruitment into draining lymph nodes is induced by certain s.c. injected adjuvants, including mature vaccine dendritic cells (DC), and is mediated by a CXCR3-dependent pathway. Here, we show that monocyte-derived immature human DCs stimulated with polyinosinic acid:polycytidylic acid, IFN-α, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IFN-γ, α-type 1–polarized DC (αDC1), secrete profuse amounts of the CXCR3 ligand CXCL9/MIG and substantial amounts of CXCL10/IP-10 and CXCL11/I-TAC after withdrawal of maturation stimuli. In sharp contrast, no measurable production of these chemokines was found in DCs after maturation with the current gold standard maturation cocktail for human DC-based cancer vaccines consisting of TNF-α, IL-1β, IL-6, and prostaglandin-E2 (PGE2-DC). PGE2-DCs preferentially produced the Th2 and regulatory T-cell–attracting chemokines CCL17/TARC and CCL22/MDC, whereas only marginal levels of these chemokines were produced by αDC1s. Functional studies in vitro showed that supernatants from mature αDC1s actively recruited CD3−CD56+ NK cells and that adding anti-CXCL9/MIG antibodies to the αDC1 supernatant substantially reduced this recruitment. Finally, αDC1s were able to induce IFN-γ production when cocultured with resting autologous NK cells, but only if concurrent CD40 ligation was provided. These novel findings indicate that injected human αDC1-based vaccines have the potential to recruit and activate NK cells during their arrival to draining lymph nodes and that this feature may be of relevance for efficient priming of Th1 cells and CTLs. [Cancer Res 2008;68(14):5965–71]
Lack of an Association between the TGFBR1*6A Variant and Colorectal Cancer Risk
Authors: Johanna Skoglund, Bo Song, Johan Dalén, Stefan Dedorson, David Edler, Fredrik Hjern, Jörn Holm, Claes Lenander, Ulrik Lindforss, Nils Lundqvist, Hans Olivecrona, Louise Olsson, Lars Påhlman, Jörgen Rutegård, Kennet Smedh, Anders Törnqvist, Richard S. Houlston, Annika Lindblom
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Recently a common variant of the TGFBR1 gene, TGFBR1*6A, has been proposed to act as a low-penetrance tumor susceptibility allele for colorectal cancer, but data from published studies with individually low statistical power are conflicting. To further evaluate the relationship between TGFBR1*6A and colorectal cancer risk, we have conducted a large case-control study and a meta-analysis of previously published studies. Experimental Design: A total of 1,042 colorectal cancer cases and 856 population controls were genotyped for the TGFBR1*6A polymorphism. Previously published case-control studies of the relationship between TGFBR1*6A and colorectal cancer were identified, and a meta-analysis was conducted. Results: We found no evidence that homozygosity, heterozygosity or carrier status for the TGFBR1*6A allele confers an increased risk of colorectal cancer; respective odds ratios (OR) were 1.05 [95% confidence interval (95% CI), 0.83-1.32], 0.82 (95% CI, 0.34-1.99), and 0.92 (95% CI, 0.74-1.15), respectively. A meta-analysis of our case-control study and seven other studies that provided data on 2,627 colorectal cancer cases and 3,387 controls also yielded no evidence that possession of the TGFBR1*6A allele is associated with an elevated risk of colorectal cancer; pooled estimate of the OR were 1.20 (95% CI, 0.64-2.24) for homozygosity, 1.11 (95% CI, 0.96-1.29) for heterozygosity, and 1.13 (95% CI, 0.98-1.30) for carriers of TGFBR1*6A. Conclusion: Current data provide limited support for the hypothesis that sequence variation in TGFBR1 defined by the TGFBR1*6A allele confers an elevated risk of colorectal cancer.
Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan
Authors: Tony Roscioli, Erik-Jan Kamsteeg, Karen Buysse, Isabelle Maystadt, Jeroen van Reeuwijk, Christa van den Elzen, Ellen van Beusekom, Moniek Riemersma, Rolph Pfundt, Lisenka E L M Vissers, Margit Schraders, Umut Altunoglu, Michael F Buckley, Han G Brunner, Bernard Grisart, Huiqing Zhou, Joris A Veltman, Christian Gilissen, Grazia M S Mancini, Paul Delrée, Michèl A Willemsen, Danijela Petković Ramadža, David Chitayat, Christopher Bennett, Eamonn Sheridan, Els A J Peeters, Gita M B Tan-Sindhunata, Christine E de Die-Smulders, Koenraad Devriendt, Hülya Kayserili, Osama Abd El-Fattah El-Hashash, Derek L Stemple, Dirk J Lefeber, Yung-Yao Lin, Hans van Bokhoven
Journal: Nature Genetics (2012)
Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial
Authors: C. Gridelli, F. Perron, S. Palmeri, M. D'Aprile, F. Cognetti, A. Rossi, V. Gebbia, R. Pepe, E. Veltri, G. Airoma, A. Russo, P. Incoronato, A.F. Scinto, G. Palazzolo, M. Natali, V. Leonardi, C. Gallo, S. De Placido, A.R. Bianco
Journal: Annals of Oncology (1996)
Effects of cigarette smoking on reproduction
Authors: C. Dechanet, T. Anahory, J. C. Mathieu Daude, X. Quantin, L. Reyftmann, S. Hamamah, B. Hedon, H. Dechaud
Journal: Human Reproduction Update (2010)

† Results Cigarette smoking and folliculogenesis Cigarette smoking and steroidogenesis Cigarette smoking and preimplantation embryo development Cigarette smoking and Fallopian tubes Cigarette smoking and embryo implantation Cigarette smoking and uterine flow velocity Cigarette smoking and myometrial activity Factors influencing smoke effects on reproductive tract and function
Ulcer of Stomach: Acute Haematemesis: Gastrotomy: Arrest of Haemorrhage at the Bleeding Spot: Venous Thrombosis in Both Legs: Recovery
Authors: H. B. Angus
Journal: BMJ (1901)

THE following case is of interest because it raises the ques- tion of the surgical treatment of hiematemesis due to gastric ulcer.S. S., aged i9, a domestic servant, vas admiiitted into the Newcastle Royal Infirnmary on Decem-ber x5th, I900, suffering from hnematemesis.History.-She had suffered from epigastric pain, coming on two hours