tbuckley/cabot-search huggingface dataset:
EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS
Authors: Peter K. Olitsky, Frederick L. Gates
Journal: The Journal of Experimental Medicine (1921)

From the filtered nasopharyngeal washings of patients in the first 36 hours of uncomplicated epidemic influenza and rarely in later stages of the disease, we have cultivated a minute bacilloid body, Bacterium pneumosintes, 0.15 to 0.3 microns in length, of constant cultural characters and capable of indefinite propagation on artificial media. This organism, not of the nature of ordinary bacteria, was also recovered in pure culture from the unfiltered and filtered lung tissue of rabbits and guinea pigs inoculated with unfiltered and filtered nasopharyngeal washings of early influenza cases, both from the first epidemic of 1918–19 and from the second one of 1920. The organism grows only under strictly anaerobic conditions, passes Berkefeld V and N filters, and withstands the action of sterile 50 percent glycerol for a period of months. It has been recovered from cultures contaminated with a variety of ordinary bacteria such as Bacillus pfeifferi, pneumococci, streptococci, and staphylococci, and has been experimentally cultivated in symbiosis with them. Similar cultivation of control materials uniformly failed to yield growths of this organism. The materials tested consisted of the unfiltered and filtered nasopharyngeal washings of persons free from influenza, some of whom were suffering from acute coryza, the lung tissue of normal rabbits and of rabbits with bacterial respiratory infections, and the uninoculated media. The intratracheal injection in rabbits and guinea pigs of mass cultures of this organism has induced effects on the blood and lungs of these animals which are not to be distinguished from those obtained with the nasopharyngeal secretions of patients in the early hours of epidemic influenza. From the pulmonary lesions thus induced the same organism has been recovered in pure culture, and has been found to cause similar lesions on subsequent animal passage. Its pathogenicity is not lost by prolonged artificial cultivation. Our experiments indicate that the cultivable bodies obtained directly from human nasopharyngeal washings and from affected rabbit lungs are strains of the same organism. This organism appears to be the source of the reactions which occur in experimental animals—rabbits and guinea pigs—as a result of the intratracheal injection of nasopharyngeal washings obtained during the early hours of uncomplicated epidemic influenza in man.
Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer
Authors: Mary Anna Venneri, Michele De Palma, Maurilio Ponzoni, Ferdinando Pucci, Cristina Scielzo, Erika Zonari, Roberta Mazzieri, Claudio Doglioni, Luigi Naldini
Journal: Blood (2007)
Outcome of heart–lung and bilateral sequential lung transplantation for cystic fibrosis: a UK national study
Authors: J. S. Ganesh, C. A. Rogers, R. S. Bonser, N. R. Banner
Journal: European Respiratory Journal (2005)

Cystic fibrosis (CF) patients requiring transplantation for respiratory failure may undergo either heart–lung (HLT) or bilateral sequential lung (BSLT) transplantation. The choice of operation varies between surgeons, centres and countries. The current authors investigated whether operation type influenced outcome in adult CF patients transplanted in the UK between July 1995 and June 2002. Propensity scores for receipt of BSLT versus HLT were derived using logistic regression. Cox regression was used to compare survival. In total, 88 BSLTs and 93 HLTs were identified. Patient characteristics were similar overall, but HLT recipients were more likely to be on long-term oxygen therapy and to have had prior resuscitation. There were 72 deaths (29 BSLT and 43 HLT) within 4 yrs. There was a trend towards higher unadjusted survival following BSLT, but, after adjustment, no difference was found (hazard ratio = 0.77; 95% confidence interval 0.29–2.06). Time to the first rejection episode and infection rates were also similar. A total of 82% of hearts from HLT recipients were used as domino heart transplants. In conclusion, after adjusting for comorbidity, donor factors and ischaemia time, it was found that heart–lung and bilateral sequential lung transplantation achieved a similar outcome. The use of domino heart transplantation ameliorated the impact of heart–lung transplantation on total organ availability.
Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes
Authors: Utz Krug, Christoph Röllig, Anja Koschmieder, Achim Heinecke, Maria Cristina Sauerland, Markus Schaich, Christian Thiede, Michael Kramer, Jan Braess, Karsten Spiekermann, Torsten Haferlach, Claudia Haferlach, Steffen Koschmieder, Christian Rohde, Hubert Serve, Bernhard Wörmann, Wolfgang Hiddemann, Gerhard Ehninger, Wolfgang E Berdel, Thomas Büchner, Carsten Müller-Tidow
Journal: The Lancet (2010)
An age-dependent diet-modified effect of the PPARγ Pro12Ala polymorphism in children
Authors: George V. Dedoussis, Yannis Manios, Georgia Kourlaba, Stavroula Kanoni, Vasiliki Lagou, Johannah Butler, Constantina Papoutsakis, Robert A. Scott, Mary Yannakoulia, Yannis P. Pitsiladis, Joel N. Hirschhorn, Helen N. Lyon
Journal: Metabolism (2010)
Lack of major involvement of human uroplakin genes in vesicoureteral reflux: Implications for disease heterogeneity
Authors: Songshan Jiang, Jordan Gitlin, Fang-Ming Deng, Feng-Xia Liang, Andy Lee, Anthony Atala, Stuart B. Bauer, Garth D. Ehrlich, Sally A. Feather, Judith D. Goldberg, Judith A. Goodship, Timothy H.J. Goodship, Monika Hermanns, Fen Ze Hu, Katrin E. Jones, Sue Malcolm, Cathy Mendelsohn, Robert A. Preston, Alan B. Retik, Francis X. Schneck, Victoria Wright, Xiang Y. Ye, Adrian S. Woolf, Xue-Ru Wu, Harry Ostrer, Ellen Shapiro, Jun Yu, Tung-Tien Sun
Journal: Kidney International (2004)
The IL-33/ST2 axis: yet another therapeutic target in inflammatory bowel disease?
Authors: Azucena Salas
Journal: Gut (2013)

Our understanding of the mechanisms and pathways involved in human inflammatory bowel disease (IBD) has grown exponentially in recent decades, leading to the identification of a seemingly never-ending list of potential ‘drugable’ targets. We have learned from the past, however, that all that glitters is not gold and we should exercise some caution when translating results from the bench to the bedside. The most recent example of a promising target gone wrong in IBD concerns IL-17.1

We tend to assume that molecules that are up-regulated during inflammation should constitute potential targets to block. While this may seem logical at first, a more in depth understanding of the mechanisms at play reveals that: (1) during inflammation many regulated genes actually exert protective, regenerative or anti-inflammatory actions; (2) a proportion of those inflammation-dependent genes remain altered even during remission in IBD patients.2 Therefore, in addition to its over-expression, obtaining evidence of the in vivo function of a given pathway is essential before considering the development of a blocking strategy for therapeutic purposes. Unfortunately, the effects of blocking cytokines in vivo have proven highly unpredictable. Cytokines are small proteins well known for their multiple cellular sources, pleiotropic nature and highly context-dependent behaviour, making the consequences of their blockage …
Origin of Oscillatory Kinetics of Respiratory Gas Exchange in Chronic Heart Failure
Authors: Darrel P. Francis, L. Ceri Davies, Massimo Piepoli, Mathias Rauchhaus, Piotr Ponikowski, Andrew J. S. Coats
Journal: Circulation (1999)

Background —Respiratory gas exchange measurements in patients with chronic heart failure (CHF) at rest and during exercise commonly reveal prominent slow oscillations in ventilation (V̇ E ), measured oxygen uptake (V̇ o 2 ), and carbon dioxide production (V̇ co 2 ), whose origin is not clear. Voluntary simulation of periodic breathing (PB) in normals has been reported to generate a different pattern of oscillations in gas exchange from that seen in spontaneous PB. This necessitates hypothesizing that PB is caused by a primary oscillation in tissue metabolism or in cardiac output. Methods and Results —We developed an automated method by which normal controls could be guided to breathe according to a PB pattern. The resultant metabolic oscillations closely matched those seen in spontaneous PB and had several interesting properties. At low workloads (including rest), the oscillations in V̇ o 2 were as prominent as those in V̇ E in both spontaneous PB (α VO2 /α VE =0.92±0.04) and voluntary PB (0.93±0.07). However, at increased workload, the oscillations in V̇ o 2 because less prominent than those in V̇ E in spontaneous PB (intermediate workload 0.63±0.05, high workload 0.57±0.04; P &lt;0.001) and voluntary PB (intermediate 0.66±0.03, high 0.48±0.03; P &lt;0.001). There was no difference in the relative size of metabolic oscillations between voluntary and spontaneous PB at matched workloads ( P &gt;0.05 at low, intermediate, and high workloads). Furthermore, V̇ o 2 peaked before V̇ E in both spontaneous and voluntary PB. This time delay varied from 6.4±0.4 s at low ventilation, to 11.3±0.9 s at high ventilation ( P &lt;0.0001). Conclusions —The magnitude and phase pattern of oscillations in gas exchange of spontaneous PB can be obtained by adequately matched voluntary PB. Therefore, the gas exchange features of PB are explicable by primary ventilatory oscillation.
Staphylococcus aureus fibronectin-binding protein specifically binds IgE from patients with atopic dermatitis and requires antigen presentation for cellular immune responses
Authors: Kavita Reginald, Kerstin Westritschnig, Birgit Linhart, Margarete Focke-Tejkl, Beatrice Jahn-Schmid, Julia Eckl-Dorna, Annice Heratizadeh, Angelika Stöcklinger, Nadja Balic, Susanne Spitzauer, Verena Niederberger, Thomas Werfel, Josef Thalhamer, Stephan Weidinger, Natalija Novak, Markus Ollert, Alexander M. Hirschl, Rudolf Valenta
Journal: Journal of Allergy and Clinical Immunology (2011)
siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells
Authors: Dae Won Kim, Kyung-Ok Kim, Mike J Shin, Jung Hee Ha, Sung Wook Seo, Jay Yang, Francis Y Lee
Journal: Molecular Cancer (2009)

High expression of P-glycoprotein is one of the well-known mechanisms of chemoresistance in chondrosarcomas. However, the role of antiapoptotic proteins, a common mechanism responsible for chemoresistance in other tumors, has not been well studied in chondrosarcomas. We examined the importance of P-glycoprotein and antiapoptotic proteins in the chemoresistance to doxorubicin of two Grade II chondrosarcoma cell lines, JJ012 and SW1353.We confirmed that both chondrosarcoma cell types expressed P-glycoprotein and antiapoptotic proteins (Bcl-2, Bcl-xL and XIAP). siRNA knockdown as well as pharmacologic inhibitors of cell survival proteins (Bcl-2, Bcl-xL and XIAP) enhanced apoptosis of chemoresistant chondrosarcoma cells by up to 5.5 fold at 0.1 micromol and 5.5 fold at 1 micromol doxorubicin. These chemosensitizing effects were comparable to those of P-glycoprotein inhibition by siRNA or pharmacologic inhibitor.These findings suggest that antiapoptotic proteins play a significant role in the chemoresistance of chondrosarcoma cells independent of P-glycoprotein. Based on the results, a new siRNA-based therapeutic strategy targeting antiapoptotic genes can be designed to overcome the chemoresistance of chondrosarcomas which is often conferred by P-glycoprotein.
Engineered Knottin Peptides: A New Class of Agents for Imaging Integrin Expression in Living Subjects
Authors: Richard H. Kimura, Zhen Cheng, Sanjiv Sam Gambhir, Jennifer R. Cochran
Journal: Cancer Research (2009)

There is a critical need for molecular imaging agents to detect cell surface integrin receptors that are present in human cancers. Previously, we used directed evolution to engineer knottin peptides that bind with high affinity ( approximately 10 to 30 nmol/L) to integrin receptors that are overexpressed on the surface of tumor cells and the tumor neovasculature. To evaluate these peptides as molecular imaging agents, we site-specifically conjugated Cy5.5 or (64)Cu-1,4,7,10-tetra-azacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) to their N termini, and used optical and positron emission tomography (PET) imaging to measure their uptake and biodistribution in U87MG glioblastoma murine xenograft models. NIR fluorescence and microPET imaging both showed that integrin binding affinity plays a strong role in the tumor uptake of knottin peptides. Tumor uptake at 1 hour postinjection for two high-affinity (IC(50), approximately 20 nmol/L) (64)Cu-DOTA-conjugated knottin peptides was 4.47% +/- 1.21% and 4.56% +/- 0.64% injected dose/gram (%ID/g), compared with a low-affinity knottin peptide (IC(50), approximately 0.4 mumol/L; 1.48 +/- 0.53%ID/g) and c(RGDyK) (IC(50), approximately 1 mumol/L; 2.32 +/- 0.55%ID/g), a low-affinity cyclic pentapeptide under clinical development. Furthermore, (64)Cu-DOTA-conjugated knottin peptides generated lower levels of nonspecific liver uptake ( approximately 2%ID/g) compared with c(RGDyK) ( approximately 4%ID/g) 1 hour postinjection. MicroPET imaging results were confirmed by in vivo biodistribution studies. (64)Cu-DOTA-conjugated knottin peptides were stable in mouse serum, and in vivo metabolite analysis showed minimal degradation in the blood or tumor upon injection. Thus, engineered integrin-binding knottin peptides show great potential as clinical diagnostics for a variety of cancers.
HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation
Authors: Nicolas Chomont, Mohamed El-Far, Petronela Ancuta, Lydie Trautmann, Francesco A Procopio, Bader Yassine-Diab, Geneviève Boucher, Mohamed-Rachid Boulassel, Georges Ghattas, Jason M Brenchley, Timothy W Schacker, Brenna J Hill, Daniel C Douek, Jean-Pierre Routy, Elias K Haddad, Rafick-Pierre Sékaly
Journal: Nature Medicine (2009)
HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death
Authors: Scott J. Brodie, Bruce K. Patterson, Deborah A. Lewinsohn, Kurt Diem, David Spach, Phillip D. Greenberg, Stanley R. Riddell, Lawrence Corey
Journal: Journal of Clinical Investigation (2000)

We have tracked the in vivo migration and have identified in vivo correlates of cytotoxic T-lymphocyte (CTL) activity in HIV-seropositive subjects infused with autologous gene-marked CD8+ HIV-specific CTL. The number of circulating gene-marked CTL ranged from 1.6 to 3.5% shortly after infusion to less than 0.5% 2 weeks later. Gene-marked CTL were present in the lymph node at 4.5- to 11-fold excess and colocalized within parafollicular regions of the lymph node adjacent to cells expressing HIV tat fusion transcripts, a correlate of virus replication. The CTL clones expressed the CCR5 receptor and localized among HIV-infected cells expressing the ligands MIP-1α and MIP-1β, CC-chemokines produced at sites of virus replication. Aggregates of apoptotic cells and cells expressing granzyme-B localized within these same sites. In contrast, lymph node sections from untreated HIV-seropositive subjects, all with significant viral burden (> 50,000 HIV RNA copies/mL plasma), showed no CC-chemokine expression and exhibited only sporadic and randomly distributed cells expressing granzymes and/or apoptotic cells. These studies show that the infused CTL specifically migrate to sites of HIV replication and retain their antigen-specific cytolytic potential. Moreover, these studies provide a methodology that will facilitate studies of both the magnitude and functional phenotype of Ag-specific CD8+ T cells in vivo.
Cutaneous malignant melanoma, sun exposure, and sunscreen use: epidemiological evidence
Authors: S. Bastuji-Garin, T.L. Diepgen
Journal: British Journal of Dermatology (2002)

Journal Article Cutaneous malignant melanoma, sun exposure, and sunscreen use: epidemiological evidence Get access S. Bastuji‐Garin, S. Bastuji‐Garin Public Health Department, Paris XII University, Henri‐Mondor Hospital, 51 avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France *Department of Clinical Social Medicine and Dermato‐Epidemiology, University Hospital Heidelberg, Bergheimer Str. 58, 69115 Heidelberg, Germany Sylvie Bastuji‐Garin, Service de Santé Publique, Hôpital Henri‐Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France. E‐mail: sylvie.bastuji‐garin@hmn.ap‐hop‐paris.fr Search for other works by this author on: Oxford Academic Google Scholar T.L. Diepgen T.L. Diepgen Public Health Department, Paris XII University, Henri‐Mondor Hospital, 51 avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France *Department of Clinical Social Medicine and Dermato‐Epidemiology, University Hospital Heidelberg, Bergheimer Str. 58, 69115 Heidelberg, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue s61, 1 April 2002, Pages 24–30, https://doi.org/10.1046/j.1365-2133.146.s61.9.x Published: 01 April 2002
The detection of human papillomavirus DNA in skin tags
Authors: None Dianzani, None Calvieri, None Pierangeli, None Imperi, None Bucci, None Degener
Journal: British Journal of Dermatology (1998)

Human papillomavirus (HPV) is associated with benign cutaneous or mucosal lesions and with malignant tumours, but none of the HPV types has so far been related to skin tags. Skin biopsy specimens from 49 Caucasian patients suffering from the presence of multiple soft fibromas were analysed by means of dot blot hybridization and by polymerase chain reaction assays aimed at detecting all known HPV types. The results revealed the presence of HPV DNA type 6/11 in 88% of the skin tags examined. This result supports the hypothesis that HPV plays a part in the progression of cutaneous soft fibromas, as previously reported for laryngeal papillomas.
Cardiovascular and Metabolic Effects of Whole or Fractionated Gram-Negative Bacterial Endotoxin in the Unanesthetized Rhesus Monkey
Authors: MICHAEL J. REICHGOTT, KENNETH L. MELMON, RALPH P. FORSYTH, DIRK GREINEDER
Journal: Circulation Research (1973)

Rhesus monkeys were infused with endotoxin lipopolysaccharide (LPS) (10 mg/kg [LPS 10 ] or 2.5 mg/kg [LPS 2.5 ]) or with fractions of LPS containing 6.3% lipid (PS 1 ) or 0.5% lipid (PS 2 ) (2.5 mg/kg). Systemic and regional hemodynamics, leukocyte counts, blood gases, pH, and plasma bradykinin concentration were measured. Monkeys receiving LPS 10 , LPS 2.5 , or PS 1 became hypotensive (mean blood pressure -37 ± 10 mm Hg) and had decreased peripheral vascular resistance (-10% to -24% of the base line), compensated metabolic acidosis, and elevated plasma bradykinin concentrations (14 ± 6 ng/ml) 2 hours after infusion. Vasodilation occurred in coronary, hepatic, and splanchnic vasculature; vasoconstriction occurred in the spleen. Cardiac output was diverted from muscle to viscera. Monkeys receiving PS 2 were normotensive with elevated peripheral vascular resistance (+46%) and no measurable plasma bradykinin concentration. By 6 hours, marked elevation of peripheral vascular resistance developed in monkeys given LPS 10 (+113%) and LPS 2.5 (+57%). Monkeys receiving PS 1 returned to base-line values, but monkeys receiving PS 2 remained unchanged. Leukopenia (-50% to -65%) was persistent only in monkeys receiving LPS or PS 1 . Toxicity of LPS apparently depends on the lipid portions of the molecule. Vasodilation and bradykinin generation are correlated with persistent granulocytopenia. Late toxicity may be independent of early cardiovascular events.
The Regulation of Exosome Secretion: a Novel Function of the p53 Protein
Authors: Xin Yu, Sandra L. Harris, Arnold J. Levine
Journal: Cancer Research (2006)

Abstract The p53 protein responds to stress signals by regulating the transcription of a variety of genes. Some of these genes encode secreted proteins that may be involved in the communication between adjacent cells. In this study, a proteomics approach was employed to identify proteins secreted by cells in a p53-dependent manner after DNA damage. In addition to the known transcriptional targets of p53, a set of proteins encoded by genes that are not transcriptional targets of p53 were found to increase in the culture medium after p53 activation. These proteins exit the cell via small, secreted vesicles called exosomes and exosome production by cells was found to be regulated by the p53 response. A p53-regulated gene product, TSAP6, was shown to enhance exosome production in cells undergoing a p53 response to stress. Thus, the p53 pathway regulates the production of exosomes into the medium and these vesicles can communicate with adjacent cells and even cells of the immune system. (Cancer Res 2006; 66(9): 4795-801)
Cocarcinogenic Effect of Capsaicin Involves Activation of EGFR Signaling but Not TRPV1
Authors: Mun Kyung Hwang, Ann M. Bode, Sanguine Byun, Nu Ry Song, Hyong Joo Lee, Ki Won Lee, Zigang Dong
Journal: Cancer Research (2010)

Epidemiologic and animal studies revealed that capsaicin can act as a carcinogen or cocarcinogen. However, the molecular mechanisms of the cancer-promoting effects of capsaicin are not clear. Here, we report that capsaicin has a cocarcinogenic effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin carcinogenesis in vivo and is mediated through the epidermal growth factor receptor (EGFR), but not the transient receptor potential vanilloid subfamily member 1 (TRPV1). Topical application of capsaicin on the dorsal skin of 7,12-dimetylbenz(a)anthracene-initiated and TPA-promoted TRPV1 wild-type (WT) and TRPV1 knockout (KO) mice induced more and larger skin tumors in TRPV1/KO mice, suggesting a TRPV1-independent mechanism. Cyclooxygenase-2 (COX-2) was highly elevated by capsaicin treatment in tumors and murine embryonic fibroblasts from TRPV1/KO mice. Inhibitors of EGFR/MEK signaling suppressed TPA/capsaicin-induced COX-2 expression in TRPV1/KO cells, indicating that activation of EGFR and its downstream signaling is involved in COX-2 elevation. Capsaicin induced a further induction of TPA-increased COX-2 expression in EGFR/WT cells, but not in EGFR/KO cells. TPA/capsaicin cotreatment caused EGFR tyrosine phosphorylation and activated EGFR downstream signaling, including ERKs and Akt in EGFR/WT, but not EGFR/KO cells. Specific inhibition of EGFR and TRPV1 indicated that capsaicin-induced ERK activation in A431 cells was dependent on EGFR, but not TRPV1. Together, these findings suggest that capsaicin might act as a cocarcinogen in TPA-induced skin carcinogenesis through EGFR-dependent mechanisms.
INDUCTION OF TH1 AND TH2 CD4<sup>+</sup>T CELL RESPONSES:The Alternative Approaches
Authors: Stephanie L. Constant, Kim Bottomly
Journal: Annual Review of Immunology (1997)

▪ Abstract T helper lymphocytes can be divided into two distinct subsets of effector cells based on their functional capabilities and the profile of cytokines they produce. The Th1 subset of CD4 + T cells secretes cytokines usually associated with inflammation, such as IFN-γ and TNF and induces cell-mediated immune responses. The Th2 subset produces cytokines such as IL-4 and IL-5 that help B cells to proliferate and differentiate and is associated with humoral-type immune responses. The selective differentiation of either subset is established during priming and can be significantly influenced by a variety of factors. One of these factors, the cytokine environment, has been put forward as the major variable influencing Th development and is already well reviewed by others. Instead, in the current review, we focus on some of the alternative approaches for skewing Th1/Th2 responses. Specifically, we discuss the effects on Th priming of (a) using altered peptide ligands as antigens, (b) varying the dose of antigen, and (c) altering costimulatory signals. The potential importance of each of these variables to influence immune responses to pathogens in vivo is discussed throughout.