tbuckley/cabot-search huggingface dataset:
Bone Marrow Is a Reservoir for CD4+CD25+ Regulatory T Cells that Traffic through CXCL12/CXCR4 Signals
Authors: Linhua Zou, Brian Barnett, Hana Safah, Vincent F. LaRussa, Melina Evdemon-Hogan, Peter Mottram, Shuang Wei, Odile David, Tyler J. Curiel, Weiping Zou
Journal: Cancer Research (2004)

Abstract CD4+CD25+ regulatory T cells (Tregs) mediate peripheral T-cell homeostasis and contribute to self-tolerance. Their homeostatic and pathologic trafficking is poorly understood. Under homeostatic conditions, we show a relatively high prevalence of functional Tregs in human bone marrow. Bone marrow strongly expresses functional stromal-derived factor (CXCL12), the ligand for CXCR4. Human Tregs traffic to and are retained in bone marrow through CXCR4/CXCL12 signals as shown in chimeric nonobese diabetic/severe combined immunodeficient mice. Granulocyte colony-stimulating factor (G-CSF) reduces human bone marrow CXCL12 expression in vivo, associated with mobilization of marrow Tregs to peripheral blood in human volunteers. These findings show a mechanism for homeostatic Treg trafficking and indicate that bone marrow is a significant reservoir for Tregs. These data also suggest a novel mechanism explaining reduced acute graft-versus-host disease and improvement in autoimmune diseases following G-CSF treatment.
High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial
Authors: Gordon Cook, Cathy Williams, Julia M Brown, David A Cairns, Jamie Cavenagh, John A Snowden, A John Ashcroft, Marie Fletcher, Chris Parrish, Kwee Yong, Jim Cavet, Hanna Hunter, Jenny M Bird, Anna Chalmers, Sheila O'Connor, Mark T Drayson, Treen C M Morris
Journal: The Lancet Oncology (2014)
Evolutionary Origins of Human Herpes Simplex Viruses 1 and 2
Authors: Joel O. Wertheim, Martin D. Smith, Davey M. Smith, Konrad Scheffler, Sergei L. Kosakovsky Pond
Journal: Molecular Biology and Evolution (2014)

Herpesviruses have been infecting and codiverging with their vertebrate hosts for hundreds of millions of years. The primate simplex viruses exemplify this pattern of virus-host codivergence, at a minimum, as far back as the most recent common ancestor of New World monkeys, Old World monkeys, and apes. Humans are the only primate species known to be infected with two distinct herpes simplex viruses: HSV-1 and HSV-2. Human herpes simplex viruses are ubiquitous, with over two-thirds of the human population infected by at least one virus. Here, we investigated whether the additional human simplex virus is the result of ancient viral lineage duplication or cross-species transmission. We found that standard phylogenetic models of nucleotide substitution are inadequate for distinguishing among these competing hypotheses; the extent of synonymous substitutions causes a substantial underestimation of the lengths of some of the branches in the phylogeny, consistent with observations in other viruses (e.g., avian influenza, Ebola, and coronaviruses). To more accurately estimate ancient viral divergence times, we applied a branch-site random effects likelihood model of molecular evolution that allows the strength of natural selection to vary across both the viral phylogeny and the gene alignment. This selection-informed model favored a scenario in which HSV-1 is the result of ancient codivergence and HSV-2 arose from a cross-species transmission event from the ancestor of modern chimpanzees to an extinct Homo precursor of modern humans, around 1.6 Ma. These results provide a new framework for understanding human herpes simplex virus evolution and demonstrate the importance of using selection-informed models of sequence evolution when investigating viral origin hypotheses.
Fair Allocation of Intensive Care Unit Resources
Authors: Paul N. Lanken, Peter B. Terry, Diane C. Adler, Jo Ann Brooks-Brunn, Stephen W. Crawford, Marion Danis, Anthony J. Fedullo, Jonathan E. Gottlieb, John Hansen-Flaschen, Marin H. Kollef, Francois Lemaire, John M. Luce, Molly L. Osborne, Harold L. Paz, John Popovitch, Thomas A. Raffin, Charles L. Rice, Terry R. Rogers, Mark J. Rosen, Gordon D. Rubenfeld, James H. Shelhamer, William J. Sibbald, Gordon L. Snider, John L. Stauffer, Robert D. Truog, Joseph E. Vincent, Benjamin S. Wilfond, George J. Annas, John D. Arras, David A. Asch, Arthur L. Caplan
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

T HIS OFFICIAL STATEMENT OF THE A MERICAN T HORACIC S OCIETY WAS ADOPTED BY THE ATS B OARD OF D IRECTORS , M ARCH 1997. SUMMARY American Thoracic Society (ATS) members, as health care practitioners caring for critically ill patients in intensive care units (ICUs) or as ICU directors, commonly must make decisions that allocate ICU resources. Some decisions necessitate prioritization of ICU beds while others limit access to particular scarce resources. Although these decisions arise when providing medical care for ICU patients, they occur in a larger context that includes ethical, economic, social, and legal considerations. In this context health care systems in the United States and in other countries face the consequences of increasing demand for expensive health care services in times of limited financial resources and competing societal needs. If one accepts the premise that demand for health care resources will inevitably outstrip financial constraints, one then must face the basic question of how to allocate those resources fairly. How health care organizations will meet increasing demand for services within financial constraints raises specific questions relating to the fair allocation of ICU resources:
Increased Mortality Among Persons Infected With Hepatitis C Virus
Authors: Lars Haukali Omland, Peter Jepsen, Henrik Krarup, Kristian Schønning, Bent Lind, Hans Kromann–Andersen, Keld Mikkelsen Homburg, Peer Brehm Christensen, Henrik Toft Sørensen, Niels Obel
Journal: Clinical Gastroenterology and Hepatology (2010)
Tumor-Promoting Effects of Myeloid-Derived Suppressor Cells Are Potentiated by Hypoxia-Induced Expression of miR-210
Authors: Muhammad Zaeem Noman, Bassam Janji, Shijun Hu, Joseph C. Wu, Fabio Martelli, Vincenzo Bronte, Salem Chouaib
Journal: Cancer Research (2015)

Myeloid-derived suppressor cells (MDSC) contribute significantly to the malignant characters conferred by hypoxic tumor microenvironments. However, selective biomarkers of MDSC function in this critical setting have not been defined. Here, we report that miR-210 expression is elevated by hypoxia-inducible factor-1α (HIF1α) in MDSC localized to tumors, compared with splenic MDSC from tumor-bearing mice. In tumor MDSC, we determined that HIF1α was bound directly to a transcriptionally active hypoxia-response element in the miR-210 proximal promoter. miR-210 overexpression was sufficient to enhance MDSC-mediated T-cell suppression under normoxic conditions, while targeting hypoxia-induced miR-210 was sufficient to decrease MDSC function against T cells. Mechanistic investigations revealed that miR-210 modulated MDSC function by increasing arginase activity and nitric oxide production, without affecting reactive oxygen species, IL6, or IL10 production or expression of PD-L1. In splenic MDSC, miR-210 regulated Arg1, Cxcl12, and IL16 at the levels of both mRNA and protein, the reversal of which under normoxic conditions decreased T-cell-suppressive effects and IFNγ production. Interestingly, miR-210 overexpression or targeting IL16 or CXCL12 enhanced the immunosuppressive activity of MDSC in vivo, resulting in increased tumor growth. Taken together, these results provide a preclinical rationale to explore miR-210 inhibitory oligonucleotides as adjuvants to boost immunotherapeutic responses in cancer patients.
A Phase I Study of OGX-011, a 2′-Methoxyethyl Phosphorothioate Antisense to Clusterin, in Combination with Docetaxel in Patients with Advanced Cancer
Authors: Kim N. Chi, Lillian L. Siu, Hal Hirte, Sebastien J. Hotte, Jennifer Knox, Christian Kollmansberger, Martin Gleave, Emma Guns, Jean Powers, Wendy Walsh, Dongsheng Tu, Elizabeth Eisenhauer
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Clusterin is a cytoprotective chaperone protein that promotes cell survival and confers broad-spectrum treatment resistance. OGX-011 is a 2′-methoxyethyl–modified phosphorothioate antisense oligonucleotide that is complementary to clusterin mRNA, has a prolonged tissue half life, enhances drug efficacy in xenograft models, and reduces clusterin expression in humans with a biologically effective dose of 640 mg. The objective of this study was to determine a recommended phase II dose of OGX-011 in combination with docetaxel. Experimental Design: Patients with cancers known from the literature to express clusterin were eligible. OGX-011 was given by 2-h i.v. infusion starting at 40 mg weekly after loading doses on days 1, 3, and 5. Docetaxel was given i.v. 30 mg/m2 weekly for 5 of 6 weeks (schedule A) or 75 mg/m2 every 3 weeks (schedule B). All patients had serial samples of peripheral blood mononuclear cells and serum assessed for clusterin expression. Results: Forty patients were enrolled to eight cohorts. OGX-011 could be given at the full biologically effective single-agent dose of 640 mg with both docetaxel schedules. Toxic effects were primarily myelosuppression, fatigue, hair loss, gastrointestinal effects (expected docetaxel effects), as well as dose-related chills and fever (expected OGX-011 effects). OGX-011 AUC and Cmax increased proportionally with no apparent effect on docetaxel pharmacokinetics. At the end of cycle 1, serum clusterin showed mean decreases of 34% and 38% (range, 15-99%) at the 640-mg dose levels. Conclusions: OGX-011 can be given at a biologically effective dose with standard doses of docetaxel. Phase II trials of combined OGX-011 and chemotherapy are ongoing in patients with prostate, breast, and lung cancers.
Profiles of Intermediary Metabolites in Insulki-dependent Pregnant Diabetic Women With or Without Endogenous Insulin Production
Authors: M Stangenberg, B Persson, B B Fredholm, N O Lunell
Journal: Diabetes Care (1982)

The levels of glucose, free fatty acids (FFA), glycerol, 3-hydroxybutyrate (3-HB), cyclic AMP, and Cpeptide immunoreactivity (CPR) were determined in venous plasma samples taken every half hour during an 8-h period under standardized conditions in 10 insulin-dependent pregnant women. The metabolic profiles were determined in each trimester of pregnancy. The women were divided into two groups, one with (group I: 3B, 1C, and ID according to White's classification) and one without (group II: IB, 3C, and ID) measurable plasma CPR levels. Plasma glucose values were significantly higher (P &amp;lt; 0.01) with greater variability in group II than in group I in the first and second trimesters, while no such difference was found in the third trimester of pregnancy. FFA, glycerol, 3-HB, and cyclic AMP levels were not different between the groups in any trimester of pregnancy. Amniotic fluid CPR was higher and skinfold thickness of the newborn greater in group II than in group I. Neonatal complications occurred only in infants of group II mothers. It is concluded that determination of plasma CPR in diabetic women in early pregnancy could give additional prognostic information to that obtained by the White classification.
Effects of antihypertensive treatment after acute stroke in the Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial
Authors: Thompson G Robinson, John F Potter, Gary A Ford, Christopher J Bulpitt, Julia Chernova, Carol Jagger, Martin A James, Joanne Knight, Hugh S Markus, Amit K Mistri, Neil R Poulter
Journal: The Lancet Neurology (2010)
Health-Related Quality-of-Life Findings for the Prostate Cancer Prevention Trial
Authors: C. M. Moinpour, A. K. Darke, G. W. Donaldson, D. Cespedes, C. R. Johnson, P. A. Ganz, D. L. Patrick, J. E. Ware, S. A. Shumaker, F. L. Meyskens, I. M. Thompson
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundThe Prostate Cancer Prevention Trial (PCPT)—a randomized placebo-controlled study of the efficacy of finasteride in preventing prostate cancer—offered the opportunity to prospectively study effects of finasteride and other covariates on the health-related quality of life of participants in a multiyear trial.
Disgust, politics, and responses to threat
Authors: Yoel Inbar, David Pizarro
Journal: Behavioral and Brain Sciences (2014)

Abstract We address two questions regarding the relationship between political ideology and responses to threatening or aversive stimuli. The first concerns the reason for the connection between disgust and specific political and moral attitudes; the second concerns the observation that some responses to threat (i.e., neuroticism/anxiety) are associated with a more left-wing political orientation.
AN APPRECIATION OF PAUL DUDLEY WHITE, 1886-1973
Authors: J. WILLIS HURST
Journal: Circulation (1974)

Dr. J. Willis Hurst was the last Cardiac Fellow of Dr. White at the Massachusetts General Hospital (1947-49). He is a recent past president of the American Heart Association and a Member of the National Advisory Heart and Lung Council. He is presently professor and chairman of the Department of Medicine at Emory University. The article which follows contains Dr. Hurst's remnarks at the Memorial Service for Dr. White in the Harvard Memorial Chapel, Cambridge, Massachusetts on November 13, 1973. Dr. White died on October 31, 1973.
Bidirectional Crosstalk between Leptin and Insulin-like Growth Factor-I Signaling Promotes Invasion and Migration of Breast Cancer Cells via Transactivation of Epidermal Growth Factor Receptor
Authors: Neeraj K. Saxena, LaTonia Taliaferro-Smith, Brandi B. Knight, Didier Merlin, Frank A. Anania, Ruth M. O'Regan, Dipali Sharma
Journal: Cancer Research (2008)

Abstract Obesity is an independent risk factor for breast cancer, and obese breast cancer patients exhibit a higher risk for larger tumor burden and increased metastasis. Obesity, as associated with metabolic syndrome, results in an increase in circulating insulin-like growth factor (IGF), which acts as a mitogen. In addition, higher plasma level of adipocytokine leptin is associated with obesity. In the present study, we show that cotreatment with leptin and IGF-I significantly increases proliferation as well as invasion and migration of breast cancer cells. We found a novel bidirectional crosstalk between leptin and IGF-I signaling; IGF-I induced phosphorylation of leptin receptor (Ob-Rb) and leptin induced phosphorylation of IGF-I receptor (IGF-IR), whereas cotreatment induced synergistic phosphorylation and association of Ob-Rb and IGF-IR along with activation of downstream effectors, Akt and extracellular signal–regulated kinase. Leptin increased phosphorylation of IGF signaling molecules insulin-receptor substrate (IRS)-1 and IRS-2. Interestingly, we found that leptin and IGF-I cotreatment synergistically transactivated epidermal growth factor receptor (EGFR), depending on the proteolytic release of EGFR ligands, as the broad-spectrum matrix metalloproteinase inhibitor GM6001 could inhibit this effect. Using clinically relevant EGFR inhibitors, erlotinib and lapatinib, we found that inhibition of EGFR activation effectively inhibited leptin- and IGF-I–induced invasion and migration of breast cancer cells. Taken together, these data suggest a novel bidirectional crosstalk between leptin and IGF-I signaling that transactivates EGFR and promotes the metastatic properties as well as invasion and migration of breast cancer cells. Our findings indicate the possibility of using EGFR inhibitors erlotinib and lapatinib to counter the procancerous effects of leptin and IGF-I in breast cancers. [Cancer Res 2008;68(23):9712–22]
37 SUSTAINED VIROLOGIC RESPONSE (SVR) FOLLOWING RG7128 1500MG BID/PEG-IFN/RBV FOR 28 DAYS IN HCV GENOTYPE 2/3 PRIOR NON-RESPONDERS
Authors: E.J. Gane, M. Rodriguez-Torres, D.E. Nelson, I.M. Jacobson, J.G. McHutchison, A. Duca, R. Hyland, G. Hill, E. Albanis, W.T. Symonds, M.M. Berrey
Journal: Journal of Hepatology (2010)
Hypermethylation of <i>ASC/TMS1</i> Is a Sputum Marker for Late-Stage Lung Cancer
Authors: Emi Ota Machida, Malcolm V. Brock, Craig M. Hooker, Jun Nakayama, Akiko Ishida, Jun Amano, Maria A. Picchi, Steven A. Belinsky, James G. Herman, Shun'ichiro Taniguchi, Stephen B. Baylin
Journal: Cancer Research (2006)

Abstract DNA hypermethylated gene promoter sequences are extremely promising cancer markers. Their use for risk assessment, early diagnosis, or prognosis depends on the timing of this gene change during tumor progression. We studied this for the proapoptotic gene ASC/TMS1 in lung cancer and used the findings to develop a sputum marker. ASC/TMS1 protein levels are reduced in all lung cancer types (30 of 40; 75%) but not in 10 preinvasive lesions. Hypermethylation of ASC/TMS1 is also associated with invasive cancers (41 of 152 or 27.0% of all lung cancer types) with variation in incidence between histopathologic types including 32.1% (26 of 81) of adenocarcinomas, 13.2% (7 of 53) of squamous cell carcinomas, 38.5% (5 of 13) of large-cell carcinomas, and 60% (3 of 5) of small-cell lung cancers. The hypermethylation is particularly correlated with late tumor stages being present in only 14% of stage I but 60% of later-stage tumors. The incidence of ASC/TMS1 hypermethylation in sputum DNA fully mimics the tissue findings being present in only 2% (2 of 85) of high-risk, cancer-free smokers, 15% (3 of 18) of patients with stage I non–small-cell lung cancer (NSCLC), but 41% of patients with stage III NSCLC (18 of 44), including 56% (10 of 18) of those with adenocarcinoma. Importantly, sputum is positive for this marker in 24% (10 of 42) of very high risk, clinically cancer-free individuals previously resected for stage I NSCLC. Thus, hypermethylation of ASC/TMS1 is a marker for late-stage lung cancer and, in sputum, could predict prognosis in patients resected for early-stage disease. (Cancer Res 2006; 66(12): 6210-8)
Mobilization of the Active MITE Transposons mPing and Pong in Rice by Introgression from Wild Rice (Zizania latifolia Griseb.)
Authors: Xiaohui Shan, Zhenlan Liu, Zhenying Dong, Yongming Wang, Yu Chen, Xiuyun Lin, Likun Long, Fangpu Han, Yingshan Dong, Bao Liu
Journal: Molecular Biology and Evolution (2005)

Hybridization between different species plays an important role in plant genome evolution, as well as is a widely used approach for crop improvement. McClintock has predicted that plant wide hybridization constitutes a "genomic shock" whereby cryptic transposable elements may be activated. However, direct experimental evidence showing a causal relationship between plant wide hybridization and transposon mobilization has not yet been reported. The miniature-Ping (mPing) is a recently isolated active miniature inverted-repeat transposable element transposon from rice, which is mobilized by tissue culture and γ-ray irradiation. We show herein that mPing, together with its putative transposase-encoding partner, Pong, is mobilized in three homologous recombinant inbred lines (RILs), derived from hybridization between rice (cultivar Matsumae) and wild rice (Zizania latifolia Griseb.), harboring introgressed genomic DNA from wild rice. In contrast, both elements remain immobile in two lines sharing the same parentage to the RILs but possessing no introgressed DNA. Thus, we have presented direct evidence that is consistent with McClintock's insight by demonstrating a causal link between wide hybridization and transposon mobilization in rice. In addition, we report an atypical behavior of mPing/Pong mobilization in these lines, i.e., the exclusive absence of footprints after excision.
Laboratory exercise tests are not representative of the real physical activity in more severe COPD patients
Authors: Francesco Costa, Laura Malagrinò, Gianna Decusatis, Sandra Antonelli, Claudia De Simone, Sabrina Santerini, Barbara Vagaggini, Pierluigi Paggiaro
Journal: European Respiratory Journal (2012)

Background: Cardiopulmonary exercise test (CPET) is the gold standard to evaluate the exercise tolerance. Incremental shuttle walking test (ISWT) has ventilatory and metabolic responses similar to those of CPET in moderate-severe COPD. Sensewear Armband is a new device to quantify the physical activity of daily life.

AIM: to evaluate the correlations among CPET, ISWT and daily physical activity, measured by Armband, in patients with COPD of different severity.

Subject and methods: in cross sectional study 45 COPD patients (FEV1%: 52.5±17, 36 male) evaluated: CPET, ISWT, pulmonary function test (PFT), dyspnea scale (MRC), steps/day and total energy expenditure (TEE) by Armband (as a mean of a 7-day monitoring period). The patients were divided according to FEV1 (>50 % or ≤ 50 %) and MRC (≤ 2 or > 2).

Results: CPET and ISWT significantly correlated between them, better in patients with FEV1   2. In COPD patients with FEV1 >50%, steps/day (r=0.405, r=0.582) and TEE (r=0.494, r=0.615) significantly correlated with CPET and ISWT, respectively, while this did not occur in COPD patients with FEV1   2.

Conclusion: Exercise tolerance evaluated in laboratory by CPET and ISWT is representative of the real physical activity, as expressed by steps/day and TEE, in patients with moderate COPD but not in patients with severe COPD. In these patients, physical activity evaluation may offer complementary informations to the laboratory exercise assessment.
Synovial biopsy in haemochromatosis arthropathy. Histological findings and iron deposition in relation to total body iron overload.
Authors: R.J Walker, I.W Dymock, I.D Ansell, E.B Hamilton, R Williams
Journal: Annals of the Rheumatic Diseases (1972)

The existence of a specific disorder of the joints in patients with idiopathic haemochromatosis was first suggested by Schumacher (1964) and in a recent survey of our patients we found evidence of an arthropathy in 31 of 54 male patients (Dymock, Hamilton, Laws, and Williams, 1970).The joints most frequently involved were the metacarpophalangeals but larger joints were also affected and such patients may be severely disabled.Chondrocalcinosis was present in 22 ofthe 54 male patients and, although it was occasionally found without signs of joint involvement, we did find a correlation between such hyaline cartilage calcification and joint damage.Deposits of haemosiderin in the cartilage and synovium were recorded by Sheldon (1935) and these could be directly responsible for initiating joint damage.In this paper we describe the histological appear- ances and the incidence of iron deposition in the synovium obtained mainly by needle biopsy in 27 patients.Some of them were untreated and others at varying stages during or after completion of vene- section therapy.The findings are related to clinical and radiological evidence of arthropathy and to measurenients of liver and total body iron stores.
High pathological response rate in locally advanced esophageal cancer after neoadjuvant combined modality therapy: dose finding of a weekly chemotherapy schedule with protracted venous infusion of 5-fluorouracil and dose escalation of cisplatin, docetaxel and concurrent radiotherapy
Authors: F. Pasini, G. de Manzoni, C. Pedrazzani, A. Grandinetti, E. Durante, M. Gabbani, A. Tomezzoli, C. Griso, A. Guglielmi, G. Pelosi, S. Maluta, G.L. Cetto, C. Cordiano
Journal: Annals of Oncology (2005)