tbuckley/cabot-search huggingface dataset:
Cellular and molecular mechanisms involved in the regulation of eosinophil traffickingin vivo
Authors: Simon P. Hogan, Paul S. Foster
Journal: Medicinal Research Reviews (1996)

The recruitment of eosinophils to sites of allergic inflammation is a complex process that is primarily regulated by inflammatory cytokines and chemokines. These molecules act in concert to stimulate peripheral eosinophilia, regulate homing of eosinophils to the inflammed organ, and promote eosinophil-vascular endothelium interactions, extravasation, chemotaxis, and localization to the site of the inflammatory stimulus. The essential and specific role of IL-5 in regulating blood and tissue eosinophilia, and the subsequent involvement of this leukocyte in the induction of lung damage and airway dysfunction identifies IL-5 as a primary therapeutic target. Developing strategies to inhibit IL-5 production and action, such as by the delivery of inhibitory cytokines to the lung, which specifically down-regulate CD4+ TH2 cell responses and eosinophilic inflammation, may be more beneficial than the current drugs of choice for preventive treatment and in the relief of acute and chronic asthma and allergic disease.
Chemosensitivity Profiles Identify Polymorphisms in the p53 Network Genes 14-3-3τ and CD44 That Affect Sarcoma Incidence and Survival
Authors: Alexei Vazquez, Lukasz F. Grochola, Elisabeth E. Bond, Arnold J. Levine, Helge Taubert, Thomas H. Müller, Peter Würl, Gareth L. Bond
Journal: Cancer Research (2009)

The p53 regulatory network responds to cellular stresses by initiating processes such as cell cycle arrest and apoptosis. These responses inhibit cellular transformation and mediate the response to many forms of cancer therapies. Functional variants in the genes comprising this network could help identify individuals at greater risk for cancer and patients with poorer responses to therapies, but few such variants have been identified as yet. We use the NCI60 human tumor cell line anticancer drug screen in a scan of single nucleotide polymorphisms (SNP) in 142 p53 stress response genes and identify 7 SNPs that exhibit allelic differences in cellular responses to a large panel of cytotoxic chemotherapeutic agents. The greatest differences are observed for SNPs in 14-3-3tau (YWHAQ; rs6734469, P=5.6x10(-47)) and CD44 (rs187115, P=8.1x10(-24)). In soft-tissue sarcoma patients, we find that the alleles of these SNPs that associate with weaker growth responses to chemotherapeutics associate with poorer overall survival (up to 2.89 relative risk, P=0.011) and an earlier age of diagnosis (up to 10.7 years earlier, P=0.002). Our findings define genetic markers in 14-3-3tau and CD44 that might improve the treatment and prognosis of soft-tissue sarcomas.
Spontaneous regression of Friend virus-induced erythroleukemia. I. The role of the helper murine leukemia virus component.
Authors: M Dietz, S P Fouchey, C Longley, M A Rich, P Furmanski
Journal: The Journal of Experimental Medicine (1977)

The RFV strain of the Friend virus complex induces an erythroleukemia that spontaneously regresses. The tropism of regressing Friend virus complex (RFV), which is conferred by its helper MuLV component, MuLV-RF, is different from that of the conventional virus strain, CFV. RFV is NB-tropic and CFV is N-tropic. Passage of nonregressing CFV through Fv-1 incompatible Swiss/ICR mice changed the tropism of CFV from N to NB and resulted in a virus strain which induced erythroleukemia that regressed. Passage of NB-tropic CFV back through Fv-1 compatible mice maintained NB-tropism and regression. Altering the quantity or type of helper MuLV in RFV complex by addition of Ri-MuLV inhibited regression in proportion to the amount of added Ri-MuLV. These studies indicate a relationship between a change in virus tropism to NB by passage in certain hosts (e.g., Swiss/ICR mice) and the ability of Friend virus to induce erythroleukemia that spontaneously regresses. MuLV-RF isolated from the RFV complex induced lymphocytic leukemia in newborn mice which regressed and caused the regression of CFV-induced erythroleukemia. MuLV-RF is NB-tropic, contains no spleen focus-forming virus (SFFV) activity and helps SFFV form spleen foci in genetically restrictive mice. Pseudotype viruses were prepared, consisting of MuLV-RF, or other MuLV's, and SFFV derived from FV-B. The pseudotype viruses each acquired the tropism of the MuLV used in rescue. The pseudotype prepared with MuLV-RF or another NB-tropic MuLV-F, but not the virus obtained by rescue with N-tropic MuLV-F, induced erythroleukemia that spontaneously regressed. These studies demonstrate that the ability of RFV to induce erythroleukemia that spontaneously regresses is due to its helper MuLV component.
Portal Hypertension–Related Complications After Acute Portal Vein Thrombosis: Impact of Early Anticoagulation
Authors: Juan Turnes, Juan Carlos García–Pagán, Monica González, Carles Aracil, José Luís Calleja, Cristina Ripoll, Juan G. Abraldeṣ, Rafael Bañares, Cándido Villanueva, Agustín Albillos, Juan Ramón Ayuso, Rosa Gilabert, Jaime Bosch
Journal: Clinical Gastroenterology and Hepatology (2008)
Novel functional role of heat shock protein 90 in ATP-sensitive K+ channel-mediated hypoxic preconditioning
Authors: J.-D. Jiao, V. Garg, B. Yang, K. Hu
Journal: Cardiovascular Research (2007)

AimsATP-sensitive K+ (KATP) channels are implicated in the protective effect of ischaemic preconditioning (IPC). Kir6.2 has been shown to be involved in the cardioprotection of IPC. However, the mechanism by which Kir6.2-containing KATP channels protect the heart is still largely unknown. The present study was designed to explore the potential mechanism involved in KATP channel-mediated cardioprotection.
S77. Proffered paper: In vitro induced response patterns of antileukemic T-cells – characterization by combination of functional assays, spectratyping and next generation sequencing
Authors: S Reuther, P Krell, FR Schuster, C Grabrucker, A Liepert, T Kroell, HJ Kolb, A Borkhardt, R Buhmann, H Schmetzer
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts T-cell receptor (TCR) diversity is characterised by somatic alterations in the complementary determining region 3 (CDR3) of the human TCR β-chain. Complemented with the TCR alpha-chain, TCR diversity can hypothetically result in up to 1018 different TCR molecules. Myeloid
Phase I Study of Inhaled Doxorubicin for Patients with Metastatic Tumors to the Lungs
Authors: Gregory A. Otterson, Miguel A. Villalona-Calero, Sunil Sharma, Mark G. Kris, Anthony Imondi, Mirjam Gerber, Dorothy A. White, Mark J. Ratain, Joan H. Schiller, Alan Sandler, Michael Kraut, Sridhar Mani, John R. Murren
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To evaluate the toxicity profile of inhalational doxorubicin in patients with malignant disease in the lung. Experimental Design: The OncoMyst Model CDD-2a inhalation device aerosolizes compounds to particles of 2 to 3 μm and prevents exhaled aerosol from escaping into the environment. Deposition efficiency of inhaled Technetium 99m was used to predict deposition of doxorubicin and calculate dose. Treatment was repeated every 3 weeks. No more than moderate pulmonary dysfunction was permitted (forced expiratory volume in 1 s, forced vital capacity, and diffusing capacity for carbon monoxide, all &amp;gt;50% predicted; resting SaO2 &amp;gt;90%). Results: Fifty-three patients were enrolled at 13 dose levels ranging from 0.4 to 9.4 mg/m2. The most common histologic diagnoses were sarcoma (n = 19) and non–small cell lung cancer (n = 16). Dose-limiting toxicity (DLT) was observed at the 9.4 mg/m2 dose level when two of four patients experienced pulmonary DLT. Of 11 patients treated at the 7.5 mg/m2 dose level, only one showed DLT consisting of a decline in forced vital capacity of &amp;gt;20% from baseline. No significant systemic drug-related toxicity was observed. Several patients experienced declines in pulmonary function test variables, which were attributed to progressive disease. Observed activity included a partial response in a patient with metastatic soft tissue sarcoma previously treated with i.v. doxorubicin and ifosfamide. Conclusions: Inhaled doxorubicin is safe up to a dose of 7.5 mg/m2 every 3 weeks in patients with cancer who had normal to moderately impaired pulmonary function.
High Resolution Analysis and Phylogenetic Network Construction Using Complete mtDNA Sequences in Sardinian Genetic Isolates
Authors: Cristina Fraumene, Elise M. S. Belle, Loredana Castrì, Simona Sanna, Gianmaria Mancosu, Massimiliano Cosso, Francesca Marras, Guido Barbujani, Mario Pirastu, Andrea Angius
Journal: Molecular Biology and Evolution (2006)

For mitochondrial phylogenetic analysis, the best result comes from complete sequences. We therefore decided to sequence the entire mitochondrial DNA (mtDNA) (coding and D-loop regions) of 63 individuals selected in 3 small Ogliastra villages, an isolated area of eastern Sardinia: Talana, Urzulei, and Perdasdefogu. We studied at least one individual for each of the most frequent maternal genealogical lineages belonging to haplogroups H, V, J, K, T, U, and X. We found in our 63 samples, 172 and 69 sequence changes in the coding and in the D-loop region, respectively. Thirteen out of 172 sequence changes in the coding region are novel. It is our hypothesis that some of them are characteristic of the Ogliastra region and/or Sardinia. We reconstructed the phylogenetic network of the 63 complete mtDNA sequences for the 3 villages. We also drew a network including a large number of European sequences and calculated various indices of genetic diversity in Ogliastra. It appears that these small populations remained extremely isolated and genetically differentiated compared with other European populations. We also identified in our samples a never previously described subhaplogroup, U5b3, which seems peculiar to the Ogliastra region.
Are current back protectors suitable to prevent spinal injury in recreational snowboarders?
Authors: Kai-Uwe Schmitt, Bendicht Liechti, Frank I Michel, Rolf Stämpfli, Paul A Brühwiler
Journal: British Journal of Sports Medicine (2010)

Objective Back protectors for snowboarders were analysed with respect to their potential to prevent spinal injury. Design In 20 Swiss skiing resorts, athletes were interviewed on the slope. In addition, an online survey was conducted. The performance of 12 commercially available back protectors was investigated by means of mechanical testing. A currently used drop test according to standard EN1621 (motorcycle protectors), testing energy damping was supplemented by penetration tests according to standard EN1077, which reflects snowsport safety concerns. Results 6 out of 12 back protectors fulfilled the higher safety level defined in EN1621. Protectors making use of energy-absorbing layers performed particularly well. In contrast, hard shell protectors exhibited a higher potential to withstand the penetration test. The surveys confirmed that approximately 40–50% of snowboarders use a back protector. A large majority of users expect protection from severe spinal injury such as vertebral fractures or spinal cord injury. Conclusions The currently used test standards are fulfilled by many back protectors. Users, however, expect protectors to be efficient in impact scenarios that result in spinal injury, which are more severe than impacts as addressed in the current standards. This study highlights that there is a mismatch between the capabilities of current back protectors to prevent spinal injury in snowboarding and the expectations users have of these protectors.
Differences in circulating dendritic cell subtypes in cord blood and peripheral blood of healthy and allergic children
Authors: M.M. Hagendorens, D.G. Ebo, A.J. Schuerwegh, A. Huybrechs, H.P. Van Bever, C.H. Bridts, L.S. De Clerck, W.J. Stevens
Journal: Journal of Allergy and Clinical Immunology (2003)
Impact of Environmental Tobacco Smoke on the Incidence of Mutations in Epidermal Growth Factor Receptor Gene in Never-Smoker Patients With Non–Small-Cell Lung Cancer
Authors: Young Joo Lee, Byoung Chul Cho, Sun Ha Jee, Jin Wook Moon, Se Kyu Kim, Joon Chang, Kyung Young Chung, In Kyu Park, Sung Ho Choi, Joo-Hang Kim
Journal: Journal of Clinical Oncology (2009)

Purpose Active tobacco smoking has been associated with the incidence of epidermal growth factor receptor (EGFR) mutations. However, the impact of environmental tobacco smoke (ETS) on EGFR mutations has been unknown. We investigated an association between ETS exposure and EGFR mutations in never smokers with non–small-cell lung cancer (NSCLC). Patients and Methods We enrolled 179 consecutive never smokers who were newly diagnosed with NSCLC. The history of ETS exposure was obtained with a standardized questionnaire that included exposure period, place, and duration. The nucleotide sequences of exons 18 to 21 on EGFR gene were determined using nested polymerase chain reaction amplification. Results The incidence of EGFR mutations was significantly lower in patients with ETS exposure than in those without (38.5% v 61.4%; P = .008). In a logistic regression model that adjusted for sex and histology, an adjusted odds ratio (AOR) for the risk of EGFR mutations with exposure to ETS was 0.40 (95% CI, 0.20 to 0.81; P = .011). In quartile groups based on total smoker-year, the AORs for the lowest- to highest-quartile groups were 0.59 (95% CI, 0.23 to 1.49), 0.50 (95% CI, 0.17 to 1.50), 0.48 (95% CI, 0.20 to 1.18), and 0.22 (95% CI, 0.08 to 0.62; P trend = .028). Among the types of ETS exposure, adulthood ETS and household ETS were significantly associated with the incidence of EGFR mutations. Patients with ETS exposure showed a lower response rate to EGFR tyrosine kinase inhibitors than did patients without ETS exposure (24.6% v 44.8%; P = .053). Conclusion ETS exposure is negatively associated with EGFR mutations in never smokers with NSCLC.
Free-riding and the prisoner's dilemma: problems in funding economic analyses of phase III cancer clinical trials.
Authors: C L Bennett, T J Smith, S L George, B E Hillner, S Fleishman, H B Niell
Journal: Journal of Clinical Oncology (1995)

PURPOSE Both economic and clinical data on new agents are important to policy-makers who approve pharmaceuticals for widespread use. Randomized clinical trials have been used to evaluate both clinical results and total medical costs associated with new agents. With new expensive pharmaceutical agents, early assessments of economic benefit have taken on greater importance to physicians and patients. Who should provide financial support to these integrated economic and clinical analyses in clinical trials? Here we describe issues that hinder funding of economic analyses and propose potential support mechanisms. RESULTS The Cancer and Leukemia Group B (CALGB), a large, national cooperative group of academic and community hospitals in the United States, designed a non-small-cell lung cancer (NSCLC) treatment trial to compare two widely used supportive care regimens that varied 20-fold in cost. One important objective of this trial was to compare the cost-effectiveness of the two regimens. While funding for the clinical trial was supported by grants from the National Cancer Institute and the pharmaceutical companies involved in the trial, no specific funding agency was willing and/or able to provide financial support for the economic analyses. After 2 years of planning, the clinical trial was retracted when the funding for the economic analyses could not be secured. The prisoner's dilemma, individual reluctance to support a common social good, explains the lack of funding. CONCLUSION Economic theory predicts difficulties in evaluating cost-effectiveness of new pharmaceuticals and reluctance to support economic analyses of clinical trials. Economic analyses will require new sources of funds that will not take scarce resources from clinical trials groups. Options for funding include a new federal agency, coordinated work by existing agencies, or academic centers for economic analysis.
Association between self-reported childhood socioeconomic position and adult lung function: findings from the British Women's Heart and Health Study
Authors: D A Lawlor
Journal: Thorax (2004)

<b>Background:</b> A study was undertaken to assess the associations between indicators of early life socioeconomic position and lung function in older adulthood. <b>Methods:</b> The associations of self-reported indicators of childhood socioeconomic position with adult lung function (forced expiratory volume in 1 second (FEV<sub>1</sub>), forced vital capacity (FVC), and forced expiratory flow rate during mid expiration (FEF<sub>25–75</sub>), all measured using standard procedures) were assessed in a cross sectional study of 3641 British women aged 60–79 years. <b>Results:</b> In confounder adjusted analyses, each individual indicator of childhood circumstances was inversely associated with each measure of lung function. In the fully adjusted models (including mutual adjustment for each of the other indicators of childhood socioeconomic circumstances), only childhood occupational social class and access to a car were associated with lung function in adulthood. However, there were strong linear trends of worsening lung function with greater numbers of indicators of childhood poverty (all p values &lt;0.001). <b>Conclusions:</b> Childhood poverty is associated with poorer lung function in women aged 60–79 years. Adverse childhood circumstances that affect both lung growth and development and cardiovascular disease in later life may explain some of the well known associations between poor lung function and cardiovascular disease, or lung function may be an important mediating factor in this association.
Antagonist HIV-1 Gag Peptides Induce Structural Changes in HLA B8
Authors: Scott W. Reid, Steve McAdam, Kathrine J. Smith, Paul Klenerman, Chris A. O'Callaghan, Karl Harlos, Bent K. Jakobsen, Andrew J. McMichael, John I. Bell, David I. Stuart, E. Yvonne Jones
Journal: The Journal of Experimental Medicine (1996)

In the cellular immune response, recognition by CTL-TCRs of viral antigens presented as peptides by HLA class I molecules, triggers destruction of the virally infected cell (Townsend, A.R.M., J. Rothbard, F.M. Gotch, G. Bahadur, D. Wraith, and A.J. McMichael. 1986. Cell. 44:959–968). Altered peptide ligands (APLs) which antagonise CTL recognition of infected cells have been reported (Jameson, S.C., F.R. Carbone, and M.J. Bevan. 1993. J. Exp. Med. 177:1541–1550). In one example, lysis of antigen presenting cells by CTLs in response to recognition of an HLA B8–restricted HIV-1 P17 (aa 24–31) epitope can be inhibited by naturally occurring variants of this peptide, which act as TCR antagonists (Klenerman, P., S. Rowland Jones, S. McAdam, J. Edwards, S. Daenke, D. Lalloo, B. Koppe, W. Rosenberg, D. Boyd, A. Edwards, P. Giangrande, R.E. Phillips, and A. McMichael. 1994. Nature (Lond.). 369:403– 407). We have characterised two CTL clones and a CTL line whose interactions with these variants of P17 (aa 24–31) exhibit a variety of responses. We have examined the high resolution crystal structures of four of these APLs in complex with HLA B8 to determine alterations in the shape, chemistry, and local flexibility of the TCR binding surface. The variant peptides cause changes in the recognition surface by three mechanisms: changes contributed directly by the peptide, effects transmitted to the exposed peptide surface, and induced effects on the exposed framework of the peptide binding groove. While the first two mechanisms frequently lead to antagonism, the third has more profound effects on TCR recognition.
Engraftment of Bone Marrow Progenitor Cells in a Rat Model of Asbestos-Induced Pulmonary Fibrosis
Authors: Jeffrey L. Spees, Derek A. Pociask, Deborah E. Sullivan, Mandolin J. Whitney, Joseph A. Lasky, Darwin J. Prockop, Arnold R. Brody
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Bone marrow-derived cells have been shown to engraft during lung fibrosis. However, it is not known if similar cells engraft consequent to inhalation of asbestos fibers that cause pulmonary fibrosis, or if the cells proliferate and differentiate at sites of injury.We examined whether bone marrow-derived cells participate in the pulmonary fibrosis that is produced by exposure to chrysotile asbestos fibers.Adult female rats were lethally irradiated and rescued by bone marrow transplant from male transgenic rats ubiquitously expressing green fluorescent protein (GFP). Three weeks later, the rats were exposed to an asbestos aerosol for 5 hours on three consecutive days. Controls were bone marrow-transplanted but not exposed to asbestos.One day and 2.5 weeks after exposure, significant numbers of GFP-labeled male cells had preferentially migrated to the bronchiolar-alveolar duct bifurcations, the specific anatomic site at which asbestos produces the initial fibrogenic lesions. GFP-positive cells were present at the lesions as monocytes and macrophages, fibroblasts, and myofibroblasts or smooth muscle cells. Staining with antibodies to PCNA demonstrated that some of the engrafted cells were proliferating in the lesions and along the bronchioles. Negative results for TUNEL at the lesions confirmed that both PCNA-positive endogenous pulmonary cells and bone marrow-derived cells were proliferating rather than undergoing apoptosis, necrosis, or DNA repair.Bone marrow-derived cells migrated into developing fibrogenic lesions, differentiated into multiple cell types, and persisted for at least 2.5 weeks after the animals were exposed to aerosolized chrysotile asbestos fibers.
EXPERIMENTAL STUDIES ON THE DEVELOPMENT OF THE THYMUS
Authors: M. A. S. Moore, J. J. T. Owen
Journal: The Journal of Experimental Medicine (1967)

Experiments utilizing chromosome marker and histological techniques in combination with parabiosis and transplanatation procedures have demonstrated an inflow of blood-home stem cells into the chick embryo thymic rudiment. There is close similarity between the histological picture in the chick and in the mouse thymic rudiment, and it is proposed that a similar developmental process takes place in both. It may be concluded that the epithelial component of the thymic rudiment, rather than producing lymphoid cells itself, furnishes an inductive environment for the proliferation and differentiation of stem cells derived extrinsically.