tbuckley/cabot-search huggingface dataset:
Severe pulmonary hypertension in histiocytosis X: long-term improvement with bosentan
Authors: L. Kiakouama, V. Cottin, B. Etienne-Mastroïanni, C. Khouatra, M. Humbert, J.F. Cordier
Journal: European Respiratory Journal (2010)

Severe pulmonary hypertension in histiocytosis X: long-term improvement with bosentanTo the Editors:Pulmonary Langerhans' cell histiocytosis (LCH)/histiocytosis X is a rare smoking-related interstitial lung disease that predominantly affects adults aged 20-40 yrs.It is commonly associated with irreversible airflow obstruction and highly variable clinical outcomes.The disease may regress spontaneously or following smoking cessation; however, in 20-30% of cases it progresses to chronic respiratory insufficiency.Despite encouraging results in case series and reports [1], no established efficacy on disease outcomes has been demonstrated with corticosteroids, vinblastine or cladribine.Although rare in patients with early disease, severe precapillary pulmonary hypertension (PH; group 5 in the clinical classification of PH) [2] is frequent in patients with advanced pulmonary LCH.Precapillary PH was present in all 21 consecutive pulmonary LCH patients [3], and in 92% of 39 patients referred for lung transplantation [4] in two series.Lung transplantation is considered the therapy of choice for end-stage pulmonary LCH and chronic respiratory insufficiency, especially among patients who exhibit severe PH [4].Whether therapy for PH may affect long-term outcomes of disease and impact timing of transplantation is currently unknown.Here, we report the long-term improvement of LCH-associated PH in a patient treated using the dual endothelin receptor antagonist bosentan, obviating the need for lung transplantation.
Stent-Based Approach for Ventricle–to–Coronary Artery Bypass
Authors: Peter Boekstegers, Philip Raake, Rasul Al Ghobainy, Jan Horstkotte, Rabea Hinkel, Torleif Sandner, Reinhard Wichels, Franz Meisner, Eckehard Thein, Keith March, Dieter Boehm, Hermann Reichenspurner
Journal: Circulation (2002)

Ventricle-to-coronary artery bypass (VCAB) is an experimental revascularization procedure that provides predominantly systolic instead of diastolic blood flow to a coronary artery.In a pig model, a stent-based procedure (VSTENT) was developed to create a VCAB. After thoracotomy, a covered VSTENT was implanted between the left ventricle and the left anterior descending coronary artery (LAD). Distal LAD flow, regional myocardial function, and intracoronary pressures were determined at different degrees of LAD stenosis and during complete LAD occlusion. During 3 hours of LAD occlusion, VSTENT preserved net forward flow at 70+/-6% and regional myocardial function at 71+/-8% of baseline. Preservation of net flow was influenced by the positioning of the VSTENT, with higher preservation also under conditions of increased oxygen demand if a "valve-like mechanism" was present during diastole. At a hemodynamically relevant level of LAD stenosis (>70%), systolic inflow was predominant after VSTENT implantation. Changes in mean diastolic intracoronary pressure that resulted from different degrees of LAD stenosis were linearly correlated to net flow after VSTENT implantation (r=0.88; P<0.001).VSTENT for ventricle-to-coronary artery bypass was feasible and preserved 70+/-6% of baseline flow during complete LAD occlusion. The degree of preservation was dependent on the position of the VSTENT creating a valve-like mechanism during diastole. Residual diastolic blood flow through a high-grade LAD stenosis influenced net flow favorably, because diastolic backflow decreased with increasing mean diastolic intracoronary pressure.
The Critical Role of 15-Lipoxygenase-1 in Colorectal Epithelial Cell Terminal Differentiation and Tumorigenesis
Authors: Imad Shureiqi, Yuanqing Wu, Dongning Chen, Xiu L. Yang, Baoxiang Guan, Jeffrey S. Morris, Peiying Yang, Robert A. Newman, Russell Broaddus, Stanley R. Hamilton, Patrick Lynch, Bernard Levin, Susan M. Fischer, Scott M. Lippman
Journal: Cancer Research (2005)

Abstract Terminal differentiation is an important event for maintaining normal homeostasis in the colorectal epithelium, and the loss of apoptosis is an important mechanism underlying colorectal tumorigenesis. The very limited current data on the role of lipoxygenase (LOX) metabolism in tumorigenesis suggests that the oxidative metabolism of linoleic and arachidonic acid possibly shifts from producing antitumorigenic 15-LOX-1 and 15-LOX-2 products to producing protumorigenic 5-LOX and 12-LOX products. We examined whether this shift occurs in vitro in the human colon cancer cell line Caco-2 in association with the loss of terminal differentiation and apoptosis, or in vivo during the formation of colorectal adenomas in patients with familial adenomatous polyposis (FAP). Restoring terminal differentiation and apoptosis of Caco-2 cells increased the mRNA levels of 5-LOX, 15-LOX-2, and 15-LOX-1, but the only significant increases in protein expression and enzymatic activity were of 15-LOX-1. In FAP patients, 15-LOX-1 expression and activity were significantly down-regulated in adenomas (compared with paired nonneoplastic epithelial mucosa), whereas 5-LOX and 15-LOX-2 protein expressions and enzymatic activities were not. We conducted a validation study with immunohistochemical testing in a second group of FAP patients; 15-LOX-1 expression was down-regulated in colorectal adenomas (compared with nonneoplastic epithelial mucosa) in 87% (13 of 15) of this group. We confirmed the mechanistic relevance of these findings by demonstrating that ectopically restoring 15-LOX-1 expression reestablished apoptosis in Caco-2 cells. Therefore, 15-LOX-1 down-regulation rather than a shift in the balance of LOXs is likely the dominant alteration in LOX metabolism which contributes to colorectal tumorigenesis by repressing apoptosis. (Cancer Res 2005; 65(24): 11486-92)
THE WISKOTT-ALDRICH SYNDROME PROTEIN (WASP): Roles in Signaling and Cytoskeletal Organization
Authors: Scott B. Snapper, Fred S. Rosen
Journal: Annual Review of Immunology (1999)

▪ Abstract The Wiskott-Aldrich Syndrome (WAS) is a rare X-linked primary immunodeficiency that is characterized by recurrent infections, hematopoietic malignancies, eczema, and thrombocytopenia. A variety of hematopoietic cells are affected by the genetic defect, including lymphocytes, neutrophils, monocytes, and platelets. Early studies noted both signaling and cytoskeletal abnormalities in lymphocytes from WAS patients. Following the identification of WASP, the gene mutated in patients with this syndrome, and the more generally expressed WASP homologue N-WASP, studies have demonstrated that WASP-family molecules associate with numerous signaling molecules known to alter the actin cytoskeleton. WASP/N-WASP may depolymerize actin directly and/or serve as an adaptor or scaffold for these signaling molecules in a complex cascade that regulates the cytoskeleton.
REGULATION OF THE IMMUNE RESPONSE
Authors: John W. Kappler, Michael Hoffmann, Richard W. Dutton
Journal: The Journal of Experimental Medicine (1971)

The effect of passively transfered antiserum against sheep erythrocytes (SRBC) on the antigen stimulated increase of SRBC-specific plaque-forming cells (anti-SRBC-PFC) and SRBC-specific thymus-derived lymphocytes (SRBC-specific T-cells) in the mouse spleen was examined. A dose of antiserum which severely suppressed the development of anti-SRBC-PFC did not prevent the increase in SRBC-specific T-cells, as measured by their ability to cooperate in the in vitro response to trinitrophenylated (TNP) SRBC. It was shown that the insensitivity of these T-cells to antiserum could not be explained by their low antigen requirement as compared to that of PFC. In the in vivo response of mice to TNP-SRBC, antibody specific for TNP suppressed the appearance of both anti-TNP- and anti-SRBC-PFC. The presence of free SRBC specifically prevented the suppression of the anti-SRBC-PFC. These observations are consistent with opsonization by phagocytic cells as the primary means of the observed suppression of PFC development by antibody.
A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial
Authors: Patrick W Serruys, Bernard Chevalier, Dariusz Dudek, Angel Cequier, Didier Carrié, Andres Iniguez, Marcello Dominici, René J van der Schaaf, Michael Haude, Luc Wasungu, Susan Veldhof, Lei Peng, Peter Staehr, Maik J Grundeken, Yuki Ishibashi, Hector M Garcia-Garcia, Yoshinobu Onuma
Journal: The Lancet (2014)
Circulatory heat sources for canine respiratory heat exchange.
Authors: J Solway, A R Leff, I Dreshaj, N M Munoz, E P Ingenito, D Michaels, R H Ingram, J M Drazen
Journal: Journal of Clinical Investigation (1986)

We assessed the roles of the pulmonary and bronchial circulations as potential heat sources to the pulmonary airways during respiratory heat loss, by observing the changes in airstream temperature that accompanied temporary occlusion of the pulmonary or bronchial circulations. Baseline end-expiratory and end-inspiratory airstream temperatures were 35.4 +/- 0.2 degrees C (SEM) and 30.9 +/- 0.3 degrees C, respectively, among all trials. With occlusion of the lower lobe pulmonary arteries for 3 min ipsilateral end-expiratory and end-inspiratory airstream temperatures fell by 2.8 +/- 0.2 and 1.1 +/- 0.2 degrees C, respectively, during hyperpnea with room temperature air, and by 3.5 +/- 0.5 and 1.8 +/- 0.2 degrees C, respectively, during hyperpnea with frigid air. In marked contrast, interruption of the bronchial circulation for 3 min had no effect on airstream temperatures. These data indicate that under these conditions, the pulmonary circulation, but not the bronchial circulation, serves as an important local heat source for respiratory heat exchange within the pulmonary airways.
Enhanced tuberculosis outbreak investigation using whole genome sequencing and IGRA
Authors: Pieter W. Smit, Tuula Vasankari, Hanna Aaltonen, Marjo Haanperä, Nicola Casali, Harri Marttila, Jane Marttila, Päivi Ojanen, Aino Ruohola, Petri Ruutu, Francis Drobniewski, Outi Lyytikäinen, Hanna Soini
Journal: European Respiratory Journal (2014)

Whole genome sequencing (WGS) is a new powerful technology for characterisation of bacterial genomes and has been used successfully to investigate Mycobacterium tuberculosis isolates associated with tuberculosis (TB) outbreaks and to elucidate mutations conferring drug resistance [1–6]. Enhanced contact investigation and improved diagnosis and treatment of latent TB infection (LTBI) are an important strategy for TB control and elimination [7–10]. TB outbreak investigation can be enhanced by using whole genome sequencing, IGRA and social network analysis <http://ow.ly/AzxfH> We would like to thank Freek de Bruin (Leiden University Medical Centre, Leiden, the Netherlands) for creating the figures, Androulla Efstratiou (Public Health England, Colindale, UK) and Aftab Jasir (European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden) for critically reading the manuscript, and the technicians of THL Mycobacterial Reference Laboratory for excellent technical assistance. We also thank the personnel from the Infection Control Unit, School Health and Occupational Health of the City of Turku, the Chest Clinic and the Hospital Hygiene and Infection Control of Turku University Hospital.
A Content-Centric Organization of the Genetic Code
Authors: Jun Yu
Journal: Genomics Proteomics & Bioinformatics (2007)

The codon table for the canonical genetic code can be rearranged in such a way that the code is divided into four quarters and two halves according to the variability of their GC and purine contents, respectively. For prokaryotic genomes, when the genomic GC content increases, their amino acid contents tend to be restricted to the GC-rich quarter and the purine-content insensitive half, where all codons are fourfold degenerate and relatively mutation-tolerant. Conversely, when the genomic GC content decreases, most of the codons retract to the AU-rich quarter and the purine-content sensitive half; most of the codons not only remain encoding physico-chemically diversified amino acids but also vary when transversion (between purine and pyrimidine) happens. Amino acids with sixfold-degenerate codons are distributed into all four quarters and across the two halves; their fourfold-degenerate codons are all partitioned into the purine-insensitive half in favorite of robustness against mutations. The features manifested in the rearranged codon table explain most of the intrinsic relationship between protein coding sequences (the informational content) and amino acid compositions (the functional content). The renovated codon table is useful in predicting abundant amino acids and positioning the amino acids with related or distinct physico-chemical properties.
Purified Influenza Virus Vaccine
Authors: F. Bruce Peck
Journal: JAMA (1968)

The development of procedures for the use of the K-II continuous flow zonal ultracentrifuge has resulted, for the first time, in the availability of large quantities of highly purified influenza virus vaccine essentially free of nonviral egg-derived material. With these vaccines, it was determined that the inherent toxicity of purified virus strains and combinations thereof is uniformly low, and that the variable side effects frequently seen with conventionally produced vaccines are not virus related. Purified vaccines are equal in antigenicity to equivalent doses of conventional vaccines, demonstrating that nonviral components of conventional vaccine have no beneficial effects on vaccine antigenicity. Purified vaccine of twice normal potency is no more reactogenic than the same vaccine in standard doses, indicating that future vaccines of even higher potency and low reactivity are well within the realm of possibility.
Aspartate Protease From Alternaria Induced Cytokine Production, And Calcium Signaling In Human Airway Epithelial Cells Through A Protease-activated Receptor-2 (par-2)
Authors: Y. Matsuwaki, T. White, K. Hotta, Y. Inoue, C.B. Lawrence, H. Kita
Journal: Journal of Allergy and Clinical Immunology (2007)
Epitope-specific Evolution of Human CD8+ T Cell Responses from Primary to Persistent Phases of Epstein-Barr Virus Infection
Authors: Andrew D. Hislop, Nicola E. Annels, Nancy H. Gudgeon, Alison M. Leese, Alan B. Rickinson
Journal: The Journal of Experimental Medicine (2002)

Primary virus infection often elicits a large CD8+ T cell response which subsequently contracts to a smaller memory T cell pool; the relationship between these two virus-specific populations is not well understood. Here we follow the human CD8+ T cell response to Epstein-Barr virus (EBV) from its primary phase in infectious mononucleosis (IM) through to the persistent carrier state. Using HLA-A2.1 or B8 tetramers specific for four lytic cycle and three latent cycle epitopes, we find marked differences in the epitope-specific composition of the T cell populations between the two phases of infection. The primary response is dominated by lytic epitope specificities which are severely culled (and in one case extinguished) with resolution of the acute infection; in contrast latent epitope specificities are less abundant, if present at all, in acute IM but often then increase their percentage representation in the CD8 pool. Even comparing epitopes of the same type, the relative size of responses seen in primary infection does not necessarily correlate with that seen in the longer term. We also follow the evolution of phenotypic change in these populations and show that, from a uniform CD45RA−RO+CCR7− phenotype in IM, lytic epitope responses show greater reversion to a CD45RA+RO− phenotype whereas latent epitope responses remain CD45RA−RO+ with a greater tendency to acquire CCR7. Interestingly these phenotypic distinctions reflect the source of the epitope as lytic or latent, and not the extent to which the response has been amplified in vivo.
CTLA4Ig Gene Transfer Prolongs Survival and Induces Donor-Specific Tolerance in a Rat Renal Allograft
Authors: SUSANNA TOMASONI, NADIA AZZOLLINI, FEDERICA CASIRAGHI, MAURIZIO C. CAPOGROSSI, GIUSEPPE REMUZZI, ARIELA BENIGNI
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Organ transplantation requires lifelong antirejection therapy, which carries the risk of infection and cancer. A revolutionary approach is to transduce the organ graft with immunomodulatory genes to render them tolerated with no need of systemic immunosuppression. Prolonged allograft survival was achieved by adenovirus-mediated transduction of the cold-preserved kidney with sequences encoding CTLA4Ig, a recombinant fusion protein that blocks T cell activation. Organ expression of the transgene was achieved associated with mild infiltration of mononuclear cells in the transfected kidney. Mixed lymphocyte reaction as well as the production of both Th1 and Th2 cytokines were reduced. Thus, the gene transfer technique to prolong graft survival is indeed effective and safe and can induce donor-specific unresponsiveness. Pending appropriate large animal testing, ex vivo genetic manipulation of the organ before surgery may hopefully represent a major step forward in human transplant medicine.
Twist1-Mediated Adriamycin-Induced Epithelial-Mesenchymal Transition Relates to Multidrug Resistance and Invasive Potential in Breast Cancer Cells
Authors: Qing-Quan Li, Jing-Da Xu, Wen-Juan Wang, Xi-Xi Cao, Qi Chen, Feng Tang, Zhong-Qing Chen, Xiu-Ping Liu, Zu-De Xu
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Besides its therapeutic effects, chemotherapeutic agents also enhance the malignancy of treated cancers in clinical situations. Recently, epithelial-mesenchymal transition (EMT) has attracted attention in studies of tumor progression. We aimed to test whether transient Adriamycin treatment induces EMT and apoptosis simultaneously in cancer cells, clarify why the same type of cells responds differentially (i.e., apoptosis, EMT) to Adriamycin treatment, and elucidate the role of Twist1, the master regulator of EMT, in this process. Experimental Design: In unsynchronized MCF7 cells or cells synchronized at different phases, apoptosis, EMT, and concurrent events [multidrug resistance (MDR) and tumor invasion] after Adriamycin or/and Twist1 small interfering RNA treatment were examined in vitro and in vivo. The Adriamycin-induced Twist1 expression and the interaction of Twist1 with p53-Mdm2 were examined by immunoblotting and immunoprecipitation, respectively. Results: We showed in vitro that Adriamycin induced EMT and apoptosis simultaneously in a cell cycle–dependent manner. Only the cells undergoing EMT displayed enhanced invasion and MDR. Twist1 depletion completely blocked the mesenchymal transformation, partially reversed MDR, and greatly abolished invasion induced by Adriamycin. Also, we confirmed in vivo that Twist1 RNA interference improved the efficacy of Adriamycin for breast cancers. Further, Twist1 reduction in Adriamycin-treated cells promoted p53-dependent p21 induction and disrupted the association of p53 with Mdm2. Conclusions: Our studies show the diverse responses to Adriamycin treatment in cells at different phases, suggest an unrecognized role of EMT in regulating MDR and invasion, and show the efficacy of Twist1 RNA interference in Adriamycin-based chemotherapies for breast cancer.
The Effect of Macrolide Resistance on the Presentation and Outcome of Patients Hospitalized for <i>Streptococcus pneumoniae</i> Pneumonia
Authors: Catia Cilloniz, Richard K. Albert, Adamanthia Liapikou, Albert Gabarrus, Ernesto Rangel, Salvador Bello, Francesc Marco, Josep Mensa, Antoni Torres
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: There are conflicting reports describing the effect of macrolide resistance on the presentation and outcomes of patients with Streptococcus pneumoniae pneumonia.Objectives: We aimed to determine the effect of macrolide resistance on the presentation and outcomes of patients with pneumococcal pneumonia.Methods: We conducted a retrospective, observational study in the Hospital Clinic of Barcelona of all adult patients hospitalized with pneumonia who had positive cultures for S. pneumoniae from January 1, 2000 to December 31, 2013. Outcomes examined included bacteremia, pulmonary complications, acute renal failure, shock, intensive care unit admission, need for mechanical ventilation, length of hospital stay, and 30-day mortality.Measurements and Main Results: Of 643 patients hospitalized for S. pneumoniae pneumonia, 139 (22%) were macrolide resistant. Patients with macrolide-resistant organisms were less likely to have bacteremia, pulmonary complications, and shock, and were less likely to require noninvasive mechanical ventilation. We found no increase in the incidence of acute renal failure, the frequency of intensive care unit admission, the need for invasive ventilatory support, the length of hospital stay, or the 30-day mortality in patients with (invasive or noninvasive) macrolide-resistant S. pneumoniae pneumonia, and no effect on outcomes as a function of whether treatment regimens did or did not comply with current guidelines.Conclusions: We found no evidence suggesting that patients hospitalized for macrolide-resistant S. pneumoniae pneumonia were more severely ill on presentation or had worse clinical outcomes if they were treated with guideline-compliant versus noncompliant regimens.
Immunological Tolerance: The Modified Self-Recognition Hypothesis
Authors: Delta E. Uphoff
Journal: JNCI Journal of the National Cancer Institute (1969)

The functional capacity of marrow from donors in which neonatal tolerance had been induced was altered. Marrow from tolerant donors protected more lethally irradiated allogeneic recipients than syngeneic recipients. There were more long-term survivors among allogeneic recipients of tolerant marrow than among syngeneic recipients. Late mortality among syngeneic recipients of either tolerant or preinoculated nontolerant marrow resulted from a syndrome indistinguishable from the secondary disease that resulted from a graft-versus-host reaction. To explain these results a hypothesis was proposed in which immunological tolerance resulted from a modified ability to recognize “self” and “nonself.” Although tolerance was not transmitted to progeny of tolerant parents, both the modified ability to recognize “self” and the ability to be recognized as “self” were transmitted. These results were discussed in relation to the induction of tolerance by in vitro incubation of marrow with allogeneic erythrocytes before transplantation into lethally irradiated recipients.
Another Counter-Blaste
Authors: David H. Hollander
Journal: JAMA (1973)

<h3>To the Editor.—</h3> A recent note inThe Journal(220:1172, 1972) compares "the right to be free from smoke" with "the right to smoke." I have two further comments. <h3>Cigar and Pipe Smoking and Cancer.—</h3> As early as 1955, Ochsner wrote: "Prominent cancer investigators sobered by their own findings, have switched from cigarettes to pipes or cigars to reduce the risk of lung carcinomas,"1 but actually, smokers who have switched from cigarettes to cigars and pipes to avoid cancer of the lung do not avoid the risk of cancer. An association between smoking and cancer was recognized long before the invention of cigarettes. In 1851 Sir James Paget saw a patient with leukoplakia (then known as "Smoker's Patch") near the middle of the dorsal surface of the tongue where he always rested the end of his pipe, and "told him he certainly would have cancer of the tongue if he