tbuckley/cabot-search huggingface dataset:
Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity
Authors: Ya-Jen Chang, Hye Young Kim, Lee A. Albacker, Hyun Hee Lee, Nicole Baumgarth, Shizuo Akira, Paul B. Savage, Shin Endo, Takashi Yamamura, Janneke Maaskant, Naoki Kitano, Abel Singh, Apoorva Bhatt, Gurdyal S. Besra, Peter van den Elzen, Ben Appelmelk, Richard W. Franck, Guangwu Chen, Rosemarie H. DeKruyff, Michio Shimamura, Petr Illarionov, Dale T. Umetsu
Journal: Journal of Clinical Investigation (2010)

Infection with influenza A virus represents a major public health threat worldwide, particularly in patients with asthma. However, immunity induced by influenza A virus may have beneficial effects, particularly in young children, that might protect against the later development of asthma, as suggested by the hygiene hypothesis. Herein, we show that infection of suckling mice with influenza A virus protected the mice as adults against allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma. The protective effect was associated with the preferential expansion of CD4-CD8-, but not CD4+, NKT cells and required T-bet and TLR7. Adoptive transfer of this cell population into allergen-sensitized adult mice suppressed the development of allergen-induced AHR, an effect associated with expansion of the allergen-specific forkhead box p3+ (Foxp3+) Treg cell population. Influenza-induced protection was mimicked by treating suckling mice with a glycolipid derived from Helicobacter pylori (a bacterium associated with protection against asthma) that activated NKT cells in a CD1d-restricted fashion. These findings suggest what we believe to be a novel pathway that can regulate AHR, and a new therapeutic strategy (treatment with glycolipid activators of this NKT cell population) for asthma.
Pleiotrophin triggers inflammation and increased peritoneal permeability leading to peritoneal fibrosis
Authors: Hideki Yokoi, Masato Kasahara, Kiyoshi Mori, Yoshihisa Ogawa, Takashige Kuwabara, Hirotaka Imamaki, Tomoko Kawanishi, Kenichi Koga, Akira Ishii, Yukiko Kato, Keita P. Mori, Naohiro Toda, Shoko Ohno, Hisako Muramatsu, Takashi Muramatsu, Akira Sugawara, Masashi Mukoyama, Kazuwa Nakao
Journal: Kidney International (2011)
Pulmonary artery sling.
Authors: H A King, D Walker
Journal: Thorax (1984)

Pulmonary artery sling is a rare cause of respiratory distress the embryological origin of which is not known. Two patients with this abnormality, both of whom are now thriving, are described. Surgery was necessary at the age of 5 1/2 years in one child, who also had an atrial septal defect. The other child, at the age of 2 years, shows improvement of her wheezing, cough, and breathlessness despite having had neither surgical nor medical treatment.
The leukotriene-receptor antagonist MK-0679 blocks airway obstruction induced by inhaled lysine-aspirin in aspirin-sensitive asthmatics
Authors: B Dahlen, M Kumlin, DJ Margolskee, C Larsson, H Blomqvist, VC Williams, O Zetterstrom, SE Dahlen
Journal: European Respiratory Journal (1993)

Drugs which block the action or formation of the cysteinyl leukotrienes (LTC4, LTD4 and LTE4) inhibit asthmatic responses evoked by allergen, exercise and cold dry air. The purpose of this study was to determine whether the specific leukotriene-receptor antagonist MK-0679 could block the airway obstruction induced by aspirin (acetylsalicylic acid (ASA)) in aspirin-intolerant asthmatics. Eight asthmatics (mean age 45 yrs), with an average history of asthma and ASA-sensitivity of about 10 yrs duration, were subjected to bronchial provocation with lysine-ASA. Baseline ASA-sensitivity was first determined in an open prestudy session by inhalation of cumulative doses of lysine-ASA to establish the dose of ASA decreasing forced expiratory volume in one second (FEV1) by 20% (PD20). Rechallenge with lysine-ASA was performed on two different occasions, 1 h after oral administration of placebo, or 750 mg of MK-0679, under double-blind conditions, in a randomized, cross-over design. Leukotriene formation was estimated by the measurement of urinary LTE4. The lysine-ASA challenge was highly reproducible (geometric mean for group PD20 being identical for the open prestudy and the placebo session), and was associated with a post-challenge increase in urinary LTE4. In contrast, after MK-0679, there was a rightward shift in the dose response relationship for all eight subjects (median shift being 4.4 fold), with three of the subjects failing to produce a 20% decrease in FEV1 despite inhalation of the highest dose of lysine-ASA feasible to deliver.(ABSTRACT TRUNCATED AT 250 WORDS)
The inhibition of vascular smooth muscle cell migration by peptide and antibody antagonists of the alphavbeta3 integrin complex is reversed by activated calcium/calmodulin- dependent protein kinase II.
Authors: C Bilato, K A Curto, R E Monticone, R R Pauly, A J White, M T Crow
Journal: Journal of Clinical Investigation (1997)

The migration of vascular smooth muscle cells (VSMCs) is thought to play a key role in the pathogenesis of many vascular diseases and is regulated by soluble growth factors/ chemoattractants as well as interactions with the extracellular matrix. We have studied the effects of antibodies to rat beta3 and human alphavbeta3 integrins on the migration of VSMCs. Both integrin antibodies as well as cyclic RGD peptides that bind to the vitronectin receptors alphavbeta3 and alphavbeta5 significantly inhibited PDGF-directed migration. This resulted in a reduction in the accumulation of inositol (1,4,5) trisphosphate and the activation of calcium/calmodulin-dependent protein kinase II (CamKII), an important regulatory event in VSMC migration identified previously. PDGF-directed VSMC migration in the presence of the anti-integrin antibodies and cyclic RGD peptides was restored when intracellular CamKII activity was elevated by either raising intracellular calcium levels with the ionophore, ionomycin, or infecting with a replication-defective recombinant adenovirus expressing a constitutively activated CamKII cDNA (AdCMV.CKIID3). Rescue of rat VSMCs was also observed in stably transfected cell lines expressing constitutively activated but not wild-type CamKII. These observations identify a key intermediate in the regulation of VSMC migration by outside-in signaling from the integrin alphavbeta3.
Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13
Authors: Arnaud Bonnefoy, Kim Daenens, Hendrik B. Feys, Rita De Vos, Petra Vandervoort, Jos Vermylen, Jack Lawler, Marc F. Hoylaerts
Journal: Blood (2005)
Essential role of endogenous tissue plasminogen activator through matrix metalloproteinase 9 induction and expression on heparin-produced cerebral hemorrhage after cerebral ischemia in mice
Authors: Bing-Qiao Zhao, Yasuhiko Ikeda, Hayato Ihara, Tetsumei Urano, WenYing Fan, Sumiko Mikawa, Yasuhiro Suzuki, Kazunao Kondo, Kohji Sato, Nobuo Nagai, Kazuo Umemura
Journal: Blood (2003)
Enhanced cardiac PI3Kα signalling mitigates arrhythmogenic electrical remodelling in pathological hypertrophy and heart failure
Authors: Kai-Chien Yang, Patrick Y. Jay, Julie R. McMullen, Jeanne M. Nerbonne
Journal: Cardiovascular Research (2011)

AimsCardiac hypertrophy and heart failure are associated with QT prolongation and lethal ventricular arrhythmias resulting from decreased K+ current densities and impaired repolarization. Recent studies in mouse models of physiological cardiac hypertrophy revealed that increased phosphoinositide-3-kinase-α (PI3Kα) signalling results in the up-regulation of K+ channels and the normalization of ventricular repolarization. The experiments here were undertaken to test the hypothesis that increased PI3Kα signalling will counteract the adverse electrophysiological remodelling associated with pathological hypertrophy and heart failure.
THE RESPONSE OF THE SWEAT GLAND TO ACETYLCHOLINE IN ATOPIC SUBJECTS
Authors: J. A. WARNDORFF
Journal: British Journal of Dermatology (1970)

The sweat gland response to acetylcholine was measured in atopic and non‐atopic subjects throughout 1969. Atopic patients showed both an increased sensitivity and a higher production of sweat throughout the year. These findings support the assumption of a defect in the autonomic vegetative system in atopics.
A Prospective Study of Posttraumatic Stress and Depressive Reactions Among Treated and Untreated Adolescents 5 Years After a Catastrophic Disaster
Authors: Armen K Goenjian, David Walling, Alan M Steinberg, Ida Karayan, Louis M Najarian, Robert Pynoos
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: This study evaluated 1) the natural course of posttraumatic stress and depressive reactions among untreated adolescents from two cities in an earthquake zone (Gumri and Spitak) and one at the periphery (Yerevan) who were differentially exposed to the 1988 Spitak earthquake in Armenia and 2) the effectiveness of brief trauma/grief-focused psychotherapy among adolescents from Gumri. METHOD: One hundred twenty-five adolescents were assessed with the Child Posttraumatic Stress Disorder Reaction Index (CPTSD-RI) and the Depression Self-Rating Scale (DSRS) at 1.5 and 5 years postearthquake. At 1.5 years, trauma/grief-focused group and individual psychotherapy was provided over 6 weeks to a group of students in Gumri. RESULTS: CPTSD-RI scores among untreated adolescents from Gumri and Spitak subsided significantly but mildly at follow-up, with scores from Spitak, the city at the epicenter, remaining above the cutoff for a diagnosis of PTSD. DSRS scores increased mildly in both earthquake cities but only significantly in Gumri. Among treated adolescents in Gumri, improvement in CPTSD-RI scores was three times that of the untreated Gumri comparison group. The treated group also tended to improve on their DSRS scores, whereas these scores worsened significantly among untreated subjects. CONCLUSIONS: Untreated adolescents exposed to severe trauma are at risk for chronic PTSD and depressive symptoms. Brief trauma/grief-focused psychotherapy is effective in reducing PTSD symptoms and halting the progression of depression. This study supports the implementation of mental health intervention programs in schools after disasters to reduce trauma-related psychopathology.
Response to: ‘Comorbidities in a Mexican mestizo cohort with established rheumatoid arthritis’ by Vega-Morales <i>et al</i>
Authors: Maxime Dougados
Journal: Annals of the Rheumatic Diseases (2013)

On behalf of the investigators of the COMORA study,1 we would like to congratulate you for the study you have conducted in Mexican mestizo …
Syk contributes to PDGF-BB-mediated migration of rat aortic smooth muscle cells via MAPK pathways
Authors: C LEE, H LEE, H KIM, H PARK, K WON, H ROH, W CHOI, B JEON, T PARK, B KIM
Journal: Cardiovascular Research (2007)

Here we investigated the role of spleen tyrosine kinase (Syk) in the migration induced by platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells (RASMC).Cell migration was determined using a Boyden chamber, by wound-healing, and by aortic ring assays. Activity of Syk, mitogen-activated protein kinase (MAPK), and heat shock protein 27 (HSP27) were tested using immunoblotting with kinase inhibitors and small interference RNAs.PDGF-BB induced binding of Syk to the PDGFbeta receptor and increased the phosphorylation of Syk and migration in RASMC. These effects of PDGF-BB were inhibited by piceatannol, an inhibitor of Syk. PDGF-BB increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38 MAPK, and HSP27, which were significantly inhibited by piceatannol and in Syk-knockdown cells. The p38 MAPK inhibitor SB203580 and ERK1/2 inhibitor PD98059 inhibited the migration, which was further inhibited by the combination of these inhibitors. SB203580, but not PD98059, inhibited the phosphorylation of HSP27 induced by PDGF-BB in RASMC. PDGF-BB-induced migration was attenuated in HSP27-knockdown cells. Kinase inhibitors and Syk-knockdown diminished PDGF-BB-induced sprout outgrowth in the aortic ring assay.These results imply that Syk is an upstream signal of the p38 MAPK/HSP27 and ERK1/2 pathways that contributes to PDGF-BB-mediated migration in RASMC.
Long‐term efficacy and safety of infliximab maintenance therapy in patients with plaque‐type psoriasis in real‐world practice
Authors: N.H. Shear, M. Hartmann, M. Toledo‐Bahena, A. Katsambas, L. Connors, Q. Chang, R. Yao, K. Nograles, Z. Popmihajlov
Journal: British Journal of Dermatology (2014)

Journal Article Long‐term efficacy and safety of infliximab maintenance therapy in patients with plaque‐type psoriasis in real‐world practice Get access N.H. Shear, N.H. Shear University of Toronto and Sunnybrook Health Sciences Centre 2075 Bayview Ave. Room M1‐737 Toronto ON Canada M4N 3M5 Correspondence Neil H. Shear. E‐mail: neil.shear@sunnybrook.ca Search for other works by this author on: Oxford Academic Google Scholar M. Hartmann, M. Hartmann Universitäts Hautklinik Heidelberg Heidelberg Germany Search for other works by this author on: Oxford Academic Google Scholar M. Toledo‐Bahena, M. Toledo‐Bahena Hospital Infantil de México Federico Gómez México City Mexico Search for other works by this author on: Oxford Academic Google Scholar A. Katsambas, A. Katsambas Hygeia Hospital Athens Greece Search for other works by this author on: Oxford Academic Google Scholar L. Connors, L. Connors Merck Sharp and Dohme Kenilworth NJU.S.A Search for other works by this author on: Oxford Academic Google Scholar Q. Chang, Q. Chang Merck Sharp and Dohme Kenilworth NJU.S.A Search for other works by this author on: Oxford Academic Google Scholar R. Yao, R. Yao Merck Sharp and Dohme Kenilworth NJU.S.A Search for other works by this author on: Oxford Academic Google Scholar K. Nograles, K. Nograles Merck Sharp and Dohme Kenilworth NJU.S.A Search for other works by this author on: Oxford Academic Google Scholar Z. Popmihajlov, Z. Popmihajlov Merck Sharp and Dohme Kenilworth NJU.S.A Search for other works by this author on: Oxford Academic Google Scholar on behalf of All REALITY investigators on behalf of All REALITY investigators Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 3, 1 September 2014, Pages 631–641, https://doi.org/10.1111/bjd.13004 Published: 01 September 2014
A Novel FRET-Based Biosensor for the Measurement of BCR-ABL Activity and Its Response to Drugs in Living Cells
Authors: Tatsuaki Mizutani, Takeshi Kondo, Stephanie Darmanin, Masumi Tsuda, Shinya Tanaka, Minoru Tobiume, Masahiro Asaka, Yusuke Ohba
Journal: Clinical Cancer Research (2010)

Abstract Purpose: To develop a novel diagnostic method for the assessment of drug efficacy in chronic myeloid leukemia (CML) patients individually, we generated a biosensor that enables the evaluation of BCR-ABL kinase activity in living cells using the principle of fluorescence resonance energy transfer (FRET). Experimental Design: To develop FRET-based biosensors, we used CrkL, the most characteristic substrate of BCR-ABL, and designed a protein in which CrkL is sandwiched between Venus, a variant of YFP, and enhanced cyan fluorescent protein, so that CrkL intramolecular binding of the SH2 domain to phosphorylated tyrosine (Y207) increases FRET efficiency. After evaluation of the properties of this biosensor by comparison with established methods including Western blotting and flow cytometry, BCR-ABL activity and its response to drugs were examined in CML patient cells. Results: After optimization, we obtained a biosensor that possesses higher sensitivity than that of established techniques with respect to measuring BCR-ABL activity and its suppression by imatinib. Thanks to its high sensitivity, this biosensor accurately gauges BCR-ABL activity in relatively small cell numbers and can also detect &amp;lt;1% minor drug-resistant populations within heterogeneous ones. We also noticed that this method enabled us to predict future onset of drug resistance as well as to monitor the disease status during imatinib therapy, using patient cells. Conclusion: In consideration of its quick and practical nature, this method is potentially a promising tool for the prediction of both current and future therapeutic responses in individual CML patients, which will be surely beneficial for both patients and clinicians. Clin Cancer Res; 16(15); 3964–75. ©2010 AACR.
Gene-gene interaction in regulatory T–cell function in atopy and asthma development in childhood
Authors: Renske W.B. Bottema, Marjan Kerkhof, Naomi E. Reijmerink, Carel Thijs, Henriette A. Smit, Constant P. van Schayck, Bert Brunekreef, Antoon J. van Oosterhout, Dirkje S. Postma, Gerard H. Koppelman
Journal: Journal of Allergy and Clinical Immunology (2010)
Nitric Oxide Inactivates the Retinoblastoma Pathway in Chronic Inflammation
Authors: Lei Ying, Anne B. Hofseth, Darren D. Browning, Mitzi Nagarkatti, Prakash S. Nagarkatti, Lorne J. Hofseth
Journal: Cancer Research (2007)

Abstract Patients with chronic inflammatory bowel disease have a high risk of colon cancer. The molecules that initiate and promote colon cancer and the cancer pathways altered remain undefined. Here, using in vitro models and a mouse model of colitis, we show that nitric oxide (NO) species induce retinoblastoma protein (pRb) hyperphosphorylation and inactivation, resulting in increased proliferation through the pRb-E2F1 pathway. NO-driven pRb hyperphosphorylation occurs through soluble guanylyl cyclase/guanosine 3′,5′-cyclic monophosphate signaling and is dependent on the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase MEK/ERK and phosphatidylinositol 3-kinase/AKT pathways. Our results reveal a link between NO and pRb inactivation and provide insight into molecules that can be targeted in the prevention of the inflammation-to-cancer sequence. [Cancer Res 2007;67(19):9286–93]
Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2
Authors: Yaoyao Du, Yue Wang, Li Wang, Bo Liu, Qingyun Tian, Chuan-ju Liu, Tao Zhang, Qingbo Xu, Yi Zhu, Oldberg Ake, Yongfen Qi, Chaochu Tang, Wei Kong, Xian Wang
Journal: Circulation Research (2011)

Vascular calcification is a significant contributor to cardiovascular morbidity and mortality. We recently reported that cartilage oligomeric matrix protein (COMP) is pivotal for maintaining the homeostasis of vascular smooth muscle cells (VSMCs). Whether COMP affects the process of vascular calcification is unknown.We aimed to test whether COMP modulates vascular calcification.VSMC calcification in vitro was induced by calcifying media containing high inorganic phosphate or calcium. In vivo medial vessel calcification was induced in rats by 5/6 nephrectomy with a high-phosphate diet or by periadventitial application of CaCl(2) to the abdominal aorta. COMP protein level was markedly reduced in both calcified VSMCs and arteries. COMP deficiency remarkably exacerbated VSMC calcification, whereas ectopic expression of COMP greatly reduced calcification. Furthermore, COMP knockdown facilitated osteogenic markers expression by VSMCs even in the absence of calcifying media. By contrast, COMP overexpression significantly inhibited high phosphate- or high calcium-induced VSMC osteochondrogenic transition. Induction of osteogenic marker expression by COMP silencing was reversed by a soluble form of bone morphogenetic protein (BMP)-2 receptor IA, which suggests a BMP-2-dependent mechanism. Our data revealed that COMP bound directly to BMP-2 through the C terminus, inhibited BMP-2 receptor binding, and blocked BMP-2 osteogenic signaling, indicating COMP inhibits osteochondrogenic transition of VSMCs at least partially through inhibiting BMP-2.Our data strongly suggest that COMP is a novel inhibitor of vascular calcification. The imbalance between the effects of COMP and BMP-2 may provide new insights into the pathophysiology of vascular calcification.
Ionizing Radiation and the Physician
Authors: J R Brown, A A Jarvis
Journal: JAMA (1963)

The increasing awareness of the medical profession and the general public of the dangers associated with ionizing radiation necessitates a thorough understanding by the physician of the uses and dangers of this hazard. In addition to their application in the fields of diagnosis and therapeutic radiology, x-rays and radioisotopes are increasingly used in research laboratories and in various industries. The effects of low levels of ionizing radiation are still uncertain and it is possible that there is a "threshold" dose at which cellular damage is evident. With the increased number of atmospheric nuclear tests the concentrations of strontium-90, cesium-137, and the shorter lived isotopes such as iodine-131 in food will increase. The present levels of these isotopes do not merit concern and their early efficient removal will assure continued low fallout levels in our major food supplies.
First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension
Authors: F. Grimminger, G. Weimann, R. Frey, R. Voswinckel, M. Thamm, D. Bölkow, N. Weissmann, W. Mück, S. Unger, G. Wensing, R. T. Schermuly, H.A. Ghofrani
Journal: European Respiratory Journal (2009)

Pulmonary hypertension (PH) is associated with impaired production of the vasodilator nitric oxide (NO). Riociguat (BAY 63-2521; Bayer Healthcare AG, Wuppertal, Germany) acts directly on soluble guanylate cyclase, stimulating the enzyme and increasing sensitivity to low NO levels. The present study evaluates riociguat safety, tolerability and efficacy in patients with moderate-to-severe PH (pulmonary arterial hypertension, distal chronic thromboembolic PH or PH with mild to moderate interstitial lung disease). The optimal tolerated dose was identified by incremental dosing in four patients with PH; pharmacodynamic and pharmacokinetic parameters were assessed following single-dose administration (2.5 mg or 1 mg) in 10 and five patients with PH, respectively. All subjects (n = 19) were analysed for safety and tolerability. Riociguat had a favourable safety profile at single doses ≤2.5 mg. It significantly improved pulmonary haemodynamic parameters and cardiac index in patients with PH in a dose-dependent manner, to a greater extent than inhaled NO. Although riociguat also had significant systemic effects and showed no pulmonary selectivity, mean systolic blood pressure remained &gt;110 mmHg. The present report is the first to describe the use of riociguat in patients with pulmonary hypertension. The drug was well-tolerated and superior to nitric oxide in efficacy and duration. Riociguat, therefore, has potential as a novel therapy for pulmonary hypertension and warrants further investigation.
Act d 12 and Act d 13: Two novel, masked, relevant allergens in kiwifruit seeds
Authors: Sofía Sirvent, Belén Cantó, Javier Cuesta-Herranz, Francisca Gómez, Natalia Blanca, Gabriela Canto, Miguel Blanca, Rosalía Rodríguez, Mayte Villalba, Oscar Palomares
Journal: Journal of Allergy and Clinical Immunology (2014)