tbuckley/cabot-search huggingface dataset:
Toll-like Receptor 7–triggered Immune Response in the Lung Mediates Acute and Long-Lasting Suppression of Experimental Asthma
Authors: Charoula Xirakia, Ourania Koltsida, Athanasios Stavropoulos, Artemis Thanassopoulou, Vassilis Aidinis, Paschalis Sideras, Evangelos Andreakos
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Toll-like receptor (TLR) 7/8 ligands are promising candidate drugs for the treatment of allergic asthma and rhinitis. Although their clinical application depends on the development of strategies for topical administration to the lung, this has not been explored in preclinical disease models.Objectives: To examine the therapeutic effectiveness, persistence of effect, and mode of action of intranasal TLR7 ligand administration in allergic airway disease.Methods: Wild-type, IFN-α receptor (IFN-αR)−/−, IFN-γ−/−, CD8−/−, TLR7−/−, and radiation-induced chimeric mice deficient in hematopoietic TLR7 expression were subjected to an established model of allergic airway disease. R-848, a specific TLR7 agonist in mice, was administered prophylactically or therapeutically and effects of treatment on helper T-cell type 2 (Th2) responses, eosinophilia, goblet cell metaplasia, and airway hyperresponsiveness were assessed.Measurements and Main Results: Intranasal R-848 administration induced a transient immune response characterized by type I interferon production and infiltration of innate immune cells into the lung. This conferred long-term suppression of allergic airway disease via two complementary molecular processes, one mediated by type I interferons and providing acute protection by directly inhibiting effector Th2 responses, and one mediated by immunoregulatory CD8+ T cells and inducing long-lasting protection by suppressing Th2 responses in an IFN-γ–dependent manner.Conclusions: Intranasal R-848 administration is an effective treatment for allergic airway disease. It hijacks an otherwise proinflammatory immune process triggered by TLR7 to mediate long-lasting disease suppression. This provides important insight into the efficacy and mode of action of TLR7 ligands in murine models of allergic airway disease and paves the way for their clinical application in humans.
Gliclazide protects 3T3L1 adipocytes against insulin resistance induced by hydrogen peroxide with restoration of GLUT4 translocation
Authors: Tatsuhiro Shimoyama, Shinya Yamaguchi, Kazuto Takahashi, Hidenori Katsuta, Eisuke Ito, Hiroyuki Seki, Kenji Ushikawa, Hiroshi Katahira, Katsuhiko Yoshimoto, Hideki Ohno, Shinya Nagamatsu, Hitoshi Ishida
Journal: Metabolism (2006)
The role of polyamines in gastric mucus synthesis inhibited by cigarette smoke or its extract
Authors: L Ma, W P Wang, J Y C Chow, S K Lam, C H Cho
Journal: Gut (2000)

Cigarette smoking was shown to delay gastric ulcer healing and reduce synthesis of mucus, which is important for gastric ulcer protection and healing. Polyamines are important in these processes.To study the effects of cigarette smoking on the synthesis of mucus and to investigate if such an effect is acting by interference with the polyamine pathway.Gastric mucosal ornithine decarboxylase activity, mucous secreting layer thickness, and ulcer size were determined after different concentrations of cigarette smoke exposure (0, 2, or 4%) in intact animals and animals with ulcers. Synthesis of mucus and ornithine decarboxylase activity and mRNA expression were also assessed in cigarette smoke extract treated MKN-28 cells.Exposure to cigarette smoke significantly reduced the thickness of the mucous secreting layer and gastric mucosal ornithine decarboxylase activity in animals with or without ulcers. Spermidine not only reversed inhibition of mucus synthesis in both intact and ulcer bearing animals but also reversed the delay in ulcer healing. Cigarette smoke extract significantly reduced mucus synthesis and ornithine decarboxylase activity but not its mRNA expression in MKN-28 cells. The reduction in mucus synthesis was restored by spermidine.Cigarette smoke and its extract repress mucus synthesis in vivo and in vitro, respectively. Reduction of ornithine decarboxylase activity in gastric mucosa is closely associated with this effect.
Partially Matched Related Donor Transplantation Can Achieve Outcomes Comparable with Unrelated Donor Transplantation for Patients with Hematologic Malignancies
Authors: Huang Xiao-Jun, Xu Lan-Ping, Liu Kai-Yan, Liu Dai-Hong, Wang Yu, Chen Huan, Chen Yu-Hong, Han Wei, Wang Jing-Zhi, Chen Yao, Zhang Xiao-Hui, Shi Hong-Xia, Wang Feng-Rong, Tang Fei-Fei
Journal: Clinical Cancer Research (2009)

The study aimed to compare the outcomes of patients undergoing hematopoietic stem cell transplantation (HSCT) from partially matched related donors (PMRD) and unrelated donors (URD) for hematologic malignancies without the use of in vitro T cell depletion.HSCT was done on 297 consecutive patients from URDs (n = 78) and PMRDs (n = 219) during the same time period. Incidences of graft-versus-host disease (GVHD), relapse, nonrelapse mortality, overall survival, and leukemia-free survival between the PMRD and URD groups were compared.All patients achieved full engraftment. The cumct65ulative incidences of grades II to IV acute GVHD in the PMRD and URD cohorts were 47% [95% confidence interval (95% CI), 33-62%] versus 31% (CI, 20-42%; P = 0.033), with a relative risk of 1.72 (95% CI, 1.01-2.94; P = 0.046). The incidence of chronic GVHD did not differ significantly between the two cohorts (P = 0.17). The 2-year incidences of nonrelapse mortality and relapse were 20% (CI, 15-26%) versus 18% (CI, 10-27%), with P = 0.98, and 12% (CI, 8-16%) versus 18% (CI, 10-27%), with P = 0.12, for the PMRD versus the URD cohort, respectively. The 4-year overall survival and leukemia-free survival were 74% (CI, 67-80%) versus 74% (CI, 62-85%), with P = 0.98, and 67% (CI, 59-75%) versus 61% (CI, 47-74%), with P = 0.74, respectively.Our comparisons show that every major end point, including relapse, nonrelapse mortality, overall survival, and leukemia-free survival, was comparable between the PMRD and the URD groups.
Arterial pulse wave velocity and left ventricular tension period in cardiac arrhythmias
Authors: J. Weinman, D. Sapoznikov, M. Eliakim
Journal: Cardiovascular Research (1971)

Journal Article Arterial pulse wave velocity and left ventricular tension period in cardiac arrhythmias Get access J. Weinman, J. Weinman From the Rogoff Laboratory for Medical Electronics, Hebrew University—Hadassah Medical School and the Department of Medicine A, Hadassah University Hospital, Jerusalem, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Sapoznikov, D. Sapoznikov 1 From the Rogoff Laboratory for Medical Electronics, Hebrew University—Hadassah Medical School and the Department of Medicine A, Hadassah University Hospital, Jerusalem, Israel 1Part of this work is included in a Ph.D thesis (by D.s.) at the Hebrew University. Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Eliakim M. Eliakim From the Rogoff Laboratory for Medical Electronics, Hebrew University—Hadassah Medical School and the Department of Medicine A, Hadassah University Hospital, Jerusalem, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 5, Issue 4, October 1971, Pages 513–523, https://doi.org/10.1093/cvr/5.4.513 Published: 01 October 1971
Immunization and Infection Change the Number of Recombination Activating Gene (Rag)-Expressing B Cells in the Periphery by Altering Immature Lymphocyte Production
Authors: Hitoshi Nagaoka, Gloria Gonzalez-Aseguinolaza, Moriya Tsuji, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2000)

Recombination activating gene (RAG) expression in peripheral B cells increases after immunization with (4-hydroxy-3-nitrophenyl) acetyl coupled to chicken gamma globulin (NP-CGG) in alum. This increase could result from reinduction of RAG expression or, alternatively, from accumulation of RAG-expressing immature B cells in the periphery. We have used mice that carry a green fluorescent protein (GFP) RAG indicator transgene (RAG2-GFP) to characterize the RAG-expressing B cells in immunized spleens. Most of the RAG2-GFP-expressing B cells in unimmunized spleen are immature B cells. Injection with NP-CGG in alum initially suppresses lymphopoiesis in the bone marrow and decreases the number of immature RAG2-GFP-expressing B cells in the spleen. Recovery of lymphopoiesis in the bone marrow coincides with accumulation of RAG-expressing immature B cells in the spleen. Most of the RAG-expressing cells that accumulate in the spleen after immunization do not proliferate and they are not germinal center cells. Neither the initial suppression of lymphopoiesis nor the subsequent accumulation of RAG-expressing cells in the spleen is antigen dependent, since similar changes are seen with alum alone. Furthermore, such changes in the numbers of developing and circulating immature lymphoid cells are seen after injection with complete Freund's adjuvant or malaria infection. Our experiments suggest that adjuvants and infectious agents cause previously unappreciated alterations in lymphopoiesis resulting in the accumulation of RAG-expressing immature B cells in the spleen.
Phase I Study of a Novel Taxane BMS-188797 in Adult Patients with Solid Malignancies
Authors: Christopher R. Garrett, Mayer N. Fishman, Randall R. Rago, Charles C. Williams, Anne M. Dellaportas, J. Joseph Mahany, Richard M. Lush, William S. Dalton, Ashwin Gollerkeri, Marvin B. Cohen, Daniel M. Sullivan
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Preclinical studies show that BMS-188797 has a broad spectrum of antitumor activity in in vitro cytotoxicity assays and tumor xenograft models. We did a phase I trial designed to determine the maximum tolerated dose and the pharmacokinetics of BMS-188797 when administered i.v. Materials and Methods: BMS-188797 was administered i.v. over 60 minutes once every 21 days to 51 patients. The initial dose cohort of 3.75 mg/m2 was set at approximately one third the lethal dose in dogs. Doses were subsequently escalated in cohorts according to a modified Fibonacci design. Results: Fifty-one patients received a total of 160 cycles of therapy. The dose-limiting toxicity of febrile neutropenia occurred in two patients at the 200 mg/m2 cohort. Moderate to severe sensory neuropathy occurred in 12 patients (24%). Four radiographic partial responses based on the Response Evaluation Criteria in Solid Tumors occurred: two in subjects with breast cancer, one in a subject with non–small cell lung cancer, and one in a subject with renal cell carcinoma. The duration of the partial responses observed were 24.1 months (renal cell carcinoma), 5.7 and 4.3 months (breast cancer), and 4.5 months (non–small cell lung cancer). Pharmacokinetics appear linear at doses through 110 mg/m2 but not at higher doses. Conclusion: The dose-limiting toxicity in this single-agent study of BMS-188797 was febrile neutropenia. The recommended phase II dose of BMS-188797 as a single agent is 175 mg/m2 i.v. for 1 hour administered every 3 weeks.
Constitutive and modulated expression of the human alpha 1 antitrypsin gene. Different transcriptional initiation sites used in three different cell types.
Authors: W Hafeez, G Ciliberto, D H Perlmutter
Journal: Journal of Clinical Investigation (1992)

alpha 1-Antitrypsin (alpha 1 AT) is plasma glycoprotein that constitutes the principle inhibitor of neutrophil elastase in tissue fluids. It has been considered a prototype for liver-derived acute phase proteins in that its concentration in plasma increases three- to fourfold during the host response to inflammation/tissue injury. However, recent studies have shown that alpha 1 AT is expressed in several types of extrahepatic cells, including mononuclear phagocytes and enterocytes, and that there are distinct transcriptional units used in hepatocytes and at least one extra-hepatic cell type, blood monocytes. In this study, we have used a combination of ribonuclease protection assays, primer elongation analysis, and transcriptional run-on assays to further characterize mechanisms of basal and modulated alpha 1 AT gene expression in hepatocytes, enterocytes, and macrophages. The hepatoma cell line HepG2, intestinal epithelial cell line Caco2, and primary cultures of human peripheral blood monocytes were used as examples of the cell types. The results indicate that there are three macrophage-specific transcriptional initiation sites upstream from a single hepatocyte-specific transcriptional initiation site. Macrophages use these sites during basal and modulated expression. Hepatoma cells use the hepatocyte-specific transcriptional initiation site during basal and modulated expression but also switch on transcription from the upstream macrophage transcriptional initiation sites during modulation by the acute phase mediator interleukin 6 (IL-6). Caco2 cells use the hepatocyte-specific transcriptional initiation site during basal expression. There is a marked increase in the use of this site and an increase in the rate of transcriptional elongation of alpha 1 AT mRNA during differentiation of Caco2 cells from crypt-type to villous-type enterocytes. Caco2 cells also switch on transcription from the upstream macrophage transcriptional initiation sites during modulation by IL-6. These results provide further evidence that there are differences in the mechanisms of constitutive and regulated expression of the alpha 1 AT gene in at least three different cell types, HepG2-derived hepatocytes, Caco2-derived enterocytes and mononuclear phagocytes.
Is shift work a risk factor for rheumatoid arthritis? The Finnish Public Sector study
Authors: S. Puttonen, T. Oksanen, J. Vahtera, J. Pentti, M. Virtanen, P. Salo, M. Kivimaki
Journal: Annals of the Rheumatic Diseases (2010)

Rheumatoid arthritis (RA) is a chronic inflammatory disease with both environmental and genetic determinants.1 Shift work, defined here as working outside regular day shifts, has been found to induce changes in the biomarkers of systemic inflammation such as leucocyte count2 3 and T cell responses.4 5 We examined whether shift work also predicts development of RA.

Participants were drawn from the Finnish Public Sector Study,6 a prospective cohort study of 70 376 local government employees who responded to a survey in 1997–2004. We excluded those who had a history of RA at baseline (n=939) or had missing data on age, sex, or self-reported work schedule (n=2035), leaving …
Once-daily fluticasone furoate (FF)/vilanterol reduces risk of severe exacerbations in asthma versus FF alone
Authors: Eric D Bateman, Paul M O'Byrne, William W Busse, Jan Lötvall, Eugene R Bleecker, Leslie Andersen, Loretta Jacques, Lucy Frith, Jessica Lim, Ashley Woodcock
Journal: Thorax (2013)

Combination therapy with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) is recommended for patients with asthma symptomatic on ICS alone. However, there is ongoing debate regarding the risk-benefit ratio of using LABA in asthma.To evaluate the effect of the addition of a novel LABA, vilanterol (VI), to a once-daily ICS, fluticasone furoate (FF), on the risk of severe asthma exacerbations in patients with uncontrolled asthma.This randomised double-blind comparative study of variable duration (≥ 24-78 weeks) was designed to finish after 330 events (each patient's first on-treatment severe asthma exacerbation). 2019 patients with asthma aged ≥ 12 years with ≥ 1 recorded exacerbation within 1 year were randomised and received FF/VI 100/25 μg or FF 100 μg, administered once daily in the evening. The primary endpoint was time to first severe exacerbation; secondary endpoints were rate of severe asthma exacerbations per patient per year and change in trough evening forced expiratory volume in 1 s (FEV1) from baseline.Compared with FF, FF/VI delayed the time to first severe exacerbation (HR 0.795, 95% CI 0.642 to 0.985) and reduced the annualised rate of severe exacerbations (rate reduction 25%, 95% CI 5% to 40%). Significantly greater improvements in trough FEV1 (p<0.001) were observed with FF/VI than with FF at weeks 12, 36, 52 and at endpoint. Both treatments were well tolerated with similar rates of treatment-related adverse events and on-treatment serious adverse events.Once-daily FF/VI reduced the risk of severe asthma exacerbations and improved lung function compared with FF alone, with good tolerability and safety profile in adolescents and adults with asthma currently receiving ICS.NCT01086384.
Association Analysis of CD40 Polymorphisms with Asthma and the Level of Serum Total IgE
Authors: Ju Hyun Park, Hun Soo Chang, Choon-Sik Park, An-Soo Jang, Byung Lae Park, Tai Youn Rhim, Soo-Taek Uh, Yong Hoon Kim, Il Yup Chung, Hyung Doo Shin
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: The CD40 protein plays important roles in cell-mediated and humoral immune responses, especially in immunoglobulin class-switching to IgE.Objectives: We tested the association of CD40 polymorphisms with the risk of asthma and the level of serum IgE and investigated the functional effect of associated polymorphisms on the expression of CD40.Methods: We identified 17 CD40 single-nucleotide polymorphisms (SNPs) in the Korean population by direct sequencing, and we genotyped 7 of these in 487 subjects with asthma and in 161 normal subjects. Cell-surface expression of CD40 for B-cell lines of various SNP genotypes was measured using flow cytometry. The effects of SNPs in the promoter and 5′-untranslated regions (UTRs) of CD40 were assessed using pGL3 luciferase and enhanced green fluorescent protein (EGFP) reporter systems, respectively.Measurements and Results: None of the SNPs was associated with asthma risk, but total serum IgE levels were associated with the −580G>A and −1C>T polymorphisms in subjects with asthma (p = 0.007 and 0.005, respectively). The total amount of IgE was highest in the −580A or −1C homozygotes. More CD40 was expressed in B cells with the −1C allele than in those with the −1T allele (p < 0.001). EGFP expression from the CD40 5′-UTR–EGFP construct was higher for the −1C allele than the −1T allele. The −580G>A SNP did not affect promoter activity, even after IFN-γ stimulation.Conclusions: CD40 gene polymorphisms exert a genetic effect on IgE production in patients with asthma through translational regulation of CD40 expression on B cells.
A rapprochement between emotion and cognition: Amygdala, emotion, and self-relevance in episodic-autobiographical memory
Authors: Angelica Staniloiu, Hans J. Markowitsch
Journal: Behavioral and Brain Sciences (2012)

Abstract Lindquist et al. remark that not all fear instances lead to heightened amygdalar activity and, instead, point to roles of the amygdala in detecting “motivationally salient “or “emotionally impactful” stimuli. By reviewing research on the amygdala's functions in episodic-autobiographical memory, we further emphasize the involvement of the amygdala in coding the subjective relevance and extracting the biological and social significance of the stimuli.
Vascular and Extravascular Volumes of the Kidney of Man
Authors: RICHARD M. EFFROS, JEROME LOWENSTEIN, DAVID S. BALDWIN, FRANCIS P. CHINARD
Journal: Circulation Research (1967)

Indicator dilution techniques were used to determine the vascular and extravascular volumes of the normal human kidney. Renal volumes were corrected to 1.73 m 2 and refer to one kidney. The renal blood volume (V IG ) averaged 34.8±3.1 ml; the water contained in the distribution volume of labeled inulin (V IN W ) averaged 48.8±9.0 ml, and that of tritiated water (V THO W ) 152±20 ml. V IN W was used as an index of the extracellular space of the kidney exclusive of the tubular lumina. V THO W was interpreted to represent the total exchangeable water content of the kidney. The interstitial volume (ΔV INT W ) and tubular-cellular volume (ΔV C W ) were derived and averaged 27.4±6.2 ml and 93.7±14.3 ml, respectively. Correction for recirculation by exponential extrapolation was studied and appears satisfactory. Evidence is presented for the existence of significant fluctuations in renal blood flow during the indicator collection intervals, and it is suggested that renal volumes be based on flows determined from the recoveries of each indicator.
Renal Effects of Aliskiren Compared With and in Combination With Irbesartan in Patients With Type 2 Diabetes, Hypertension, and Albuminuria
Authors: Frederik Persson, Peter Rossing, Henrik Reinhard, Tina Juhl, Coen D.A. Stehouwer, Casper Schalkwijk, A.H. Jan Danser, Frans Boomsma, Erik Frandsen, Hans-Henrik Parving
Journal: Diabetes Care (2009)

OBJECTIVE We investigated whether the antiproteinuric effect of the direct renin inhibitor aliskiren is comparable to that of irbesartan and the effect of the combination. RESEARCH DESIGN AND METHODS This was a double-blind, randomized, crossover trial. After a 1-month washout period, 26 patients with type 2 diabetes, hypertension, and albuminuria (&amp;gt;100 mg/day) were randomly assigned to four 2-month treatment periods in random order with placebo, 300 mg aliskiren once daily, 300 mg irbesartan once daily, or the combination using identical doses. Patients received furosemide in a stable dose throughout the study. The primary end point was a change in albuminuria. Secondary measures included change in 24-h blood pressure and glomerular filtration rate (GFR). RESULTS Placebo geometric mean albuminuria was 258 mg/day (range 84–2,361), mean ± SD 24-h blood pressure was 140/73 ± 15/8 mmHg, and GFR was 89 ± 27 ml/min per 1.73 m2. Aliskiren treatment reduced albuminuria by 48% (95% CI 27–62) compared with placebo (P &amp;lt; 0.001), not significantly different from the 58% (42–79) reduction with irbesartan treatment (P &amp;lt; 0.001 vs. placebo). Combination treatment reduced albuminuria by 71% (59–79), more than either monotherapy (P &amp;lt; 0.001 and P = 0.028). Fractional clearances of albumin were significantly reduced (46, 56, and 67% reduction vs. placebo). Twenty-four-hour blood pressure was reduced 3/4 mmHg by aliskiren (NS/P = 0.009), 12/5 mmHg by irbesartan (P &amp;lt; 0.001/P = 0.002), and 10/6 mmHg by the combination (P = 0.001/P &amp;lt; 0.001). GFR was significantly reduced 4.6 (95% CI 0.3–8.8) ml/min per 1.73 m2 by aliskiren, 8.0 (3.6–12.3) ml/min per 1.73 m2 by irbesartan, and 11.7 (7.4–15.9) ml/min per 1.73 m2 by the combination. CONCLUSIONS The combination of aliskiren and irbesartan is more antiproteinuric in type 2 diabetic patients with albuminuria than monotherapy.
ASSOCIATIONS BETWEEN DUAL ANTIPLATELET THERAPY CESSATION AND MACE DUE TO STOPPING ONE OR BOTH DRUGS: INSIGHTS FROM THE PARIS REGISTRY
Authors: Usman Baber, Mikkel Schoos, Samantha Sartori, Philippe Steg, Cono Ariti, Giora Weisz, Bernhard Witzenbichler, Timothy Henry, Annapoorna Kini, Thomas Stuckey, David Cohen, Peter B. Berger, Ioannis Iakovou, George Dangas, Ron Waksman, Mitchell Krucoff, James Hermiller, Fayaz Shawl, C Michael Gibson, Alaide Chieffo, Maria Alu, David Moliterno, Antonio Colombo, Stuart Pocock, Roxana Mehran
Journal: Journal of the American College of Cardiology (2014)
Heme oxygenase-1 protects human hepatocytes in vitro against warm and cold hypoxia
Authors: Eda Tüzüner, Liegang Liu, Masashi Shimada, Eser Yilmaz, Matthias Glanemann, Utz Settmacher, Jan M. Langrehr, Sven Jonas, Peter Neuhaus, Andreas K. Nussler
Journal: Journal of Hepatology (2004)