tbuckley/cabot-search huggingface dataset:
Eradication of hantavirus infection among laboratory rats by application of caesarian section and a foster mother technique
Authors: P. McKenna, G. van der Groen, G. Hoofd, G. Beelaert, H. Leirs, R. Verhagen, J.P. Kints, F. Cormont, F. Nisol, H. Bazin
Journal: Journal of Infection (1992)
S143 The sensations provoking cough: a qualitative investigation
Authors: F. Solari, K. Sunger, J. Yorke, A. Caress, J. A. Smith
Journal: Thorax (2011)

<h3>Background</h3> Little is known about the sensations patients feel prior to or that provoke their cough. <h3>Aims</h3> To identify, from the patient9s perspective, key descriptors that relate to the sensations provoking cough in patients diagnosed with one of the following: idiopathic cough, asthma, chronic obstructive pulmonary disease (COPD), fibrotic interstitial lung disease (ILD) and cystic fibrosis. <h3>Methods</h3> One-to-one, audio recorded, semi- structured interviews were conducted with 34 participants (7 idiopathic cough: age 40–69 years, 5 female, 6 asthma: age 42–65 years, 5 female, 7 COPD: age 52–86 years, 2 female, 7 ILD: age 58–79 years, 3 female, 7 cystic fibrosis: age 20–39 years, 2 female). Words and phrases relating to 1 of 8 top level codes, derived from the interview topic guide (triggers, sensation, sputum, emotion, location, frequency, time and relief) were extracted using simple manifest content analysis. These descriptions were then organised into similar themes. Relationships between the descriptions and themes both within and between the groups were explored. <h3>Results</h3> All groups described the sensation of a "tickle" or an "irritation" that was felt most in the throat and upper chest. Cystic fibrosis and COPD participants most commonly described feeling a "need to clear" their airways. The ILD group mostly described a "dry", "tickly" sensation. The idiopathic cough and asthma groups used a very heterogeneous set of terms regarding the sensations provoking their cough. Common across the groups is a hypersensitive response to things that may trigger their urge to cough and all groups described coughing as relieving that urge. Emotionally the sensation is associated with negative emotions, however positive feelings were also described; by some who described feeling a need to clear their airways. <h3>Conclusion</h3> The extracted list of descriptions has provided some insight into what the sensations provoking cough feel like from patient9s perspective and suggest that the sensations felt relate to the pathology of the individual9s diagnosis. The distinction between the need to clear and a sensation of a tickle or irritation could be important in understanding the mechanisms driving cough and may be important for the development of targeted interventions.
Fresh fruit intake and asthma symptoms in young British adults: confounding or effect modification by smoking?
Authors: B.K. Butland, D.P. Strachan, H.r Anderson
Journal: European Respiratory Journal (1999)

Antioxidant vitamins have been postulated as a protective factor in asthma. The associations between the frequency of fresh fruit consumption in summer, and the prevalence of self-reported asthma symptoms were investigated. The analysis was based on 5,582 males and 5,770 females, born in England, Wales and Scotland between March 3-9, 1958 and aged 33 yrs at the time of survey. The 12-month period prevalence of wheeze and frequent wheeze were inversely associated with frequent intakes of fresh fruit and salad/raw vegetables and positively associated with smoking and lower social class. After adjustment for mutual confounding and sex, associations with smoking persisted, but those with social class and salad/raw vegetable consumption lost significance. The frequency of fresh fruit intake was no longer associated with wheeze after adjustment, but was inversely associated with frequent wheeze and speech-limiting attacks. The association with frequent wheeze differed significantly between smoking groups (never, former, current) and appeared to be confined to exsmokers and current smokers. These findings support postulated associations between infrequent fresh fruit consumption and the prevalence of frequent or severe asthma symptoms in adults. Associations appeared to be restricted to smokers, with effect modification as a more likely explanation of this pattern than residual confounding by smoking.
GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes
Authors: Vissia Viglietta, Sally C. Kent, Tihamer Orban, David A. Hafler
Journal: Journal of Clinical Investigation (2002)

Insulin-dependent type 1 diabetes is an autoimmune disease mediated by T lymphocytes recognizing pancreatic islet cell antigens. Glutamic acid decarboxylase 65 (GAD65) appears to be an important autoantigen in the disease. However, T cells from both patients with type 1 diabetes and healthy subjects vigorously proliferate in response to GAD65 stimulation ex vivo, leading us to postulate that the critical event in the onset of human diabetes is the activation of autoreactive T cells. Thus, we investigated whether GAD65-reactive T cells in patients with diabetes functioned as previously activated memory T cells, no longer requiring a second, costimulatory signal for clonal expansion. We found that in patients with new-onset type 1 diabetes, GAD65-reactive T cells were strikingly less dependent on CD28 and B7-1 costimulation to enter into cell cycle and proliferate than were equivalent cells derived from healthy controls. We hypothesize that these autoreactive T cells have been activated in vivo and have differentiated into memory cells, suggesting a pathogenic role in type 1 diabetes. In addition, we observed different effects with selective blockade of either B7-1 or B7-2 molecules; B7-1 appears to deliver a negative signal by engaging CTLA-4, while B7-2 engagement of CD28 upregulates T cell proliferation and cytokine secretion.
A Controlled Trial of Renal Denervation for Resistant Hypertension
Authors: Deepak L. Bhatt, David E. Kandzari, William W. O'Neill, Ralph D'Agostino, John M. Flack, Barry T. Katzen, Martin B. Leon, Minglei Liu, Laura Mauri, Manuela Negoita, Sidney A. Cohen, Suzanne Oparil, Krishna Rocha-Singh, Raymond R. Townsend, George L. Bakris
Journal: New England Journal of Medicine (2014)

Prior unblinded studies have suggested that catheter-based renal-artery denervation reduces blood pressure in patients with resistant hypertension.We designed a prospective, single-blind, randomized, sham-controlled trial. Patients with severe resistant hypertension were randomly assigned in a 2:1 ratio to undergo renal denervation or a sham procedure. Before randomization, patients were receiving a stable antihypertensive regimen involving maximally tolerated doses of at least three drugs, including a diuretic. The primary efficacy end point was the change in office systolic blood pressure at 6 months; a secondary efficacy end point was the change in mean 24-hour ambulatory systolic blood pressure. The primary safety end point was a composite of death, end-stage renal disease, embolic events resulting in end-organ damage, renovascular complications, or hypertensive crisis at 1 month or new renal-artery stenosis of more than 70% at 6 months.A total of 535 patients underwent randomization. The mean (±SD) change in systolic blood pressure at 6 months was -14.13±23.93 mm Hg in the denervation group as compared with -11.74±25.94 mm Hg in the sham-procedure group (P<0.001 for both comparisons of the change from baseline), for a difference of -2.39 mm Hg (95% confidence interval [CI], -6.89 to 2.12; P=0.26 for superiority with a margin of 5 mm Hg). The change in 24-hour ambulatory systolic blood pressure was -6.75±15.11 mm Hg in the denervation group and -4.79±17.25 mm Hg in the sham-procedure group, for a difference of -1.96 mm Hg (95% CI, -4.97 to 1.06; P=0.98 for superiority with a margin of 2 mm Hg). There were no significant differences in safety between the two groups.This blinded trial did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal-artery denervation as compared with a sham control. (Funded by Medtronic; SYMPLICITY HTN-3 ClinicalTrials.gov number, NCT01418261.).
Transcription coactivator mediator subunit MED1 Is required for the development of fatty liver in the mouse
Authors: Liang Bai, Yuzhi Jia, Navin Viswakarma, Jiansheng Huang, Aurore Vluggens, Nathan E. Wolins, Nadereh Jafari, Sambasiva M. Rao, Jayme Borensztajn, Gongshe Yang, Janardan K. Reddy
Journal: Hepatology (2011)

Peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor, when overexpressed in liver stimulates the induction of adipocyte-specific and lipogenesis-related genes and causes hepatic steatosis. We report here that Mediator 1 (MED1; also known as PBP or TRAP220), a key subunit of the Mediator complex, is required for high-fat diet-induced hepatic steatosis as well as PPARγ-stimulated adipogenic hepatic steatosis. Mediator forms the bridge between transcriptional activators and RNA polymerase II. MED1 interacts with nuclear receptors such as PPARγ and other transcriptional activators. Liver-specific MED1 knockout (MED1δLiv) mice, when fed a high-fat (60% kcal fat) diet for up to 4 months failed to develop fatty liver. Similarly, MED1δLiv mice injected with adenovirus-PPARγ (Ad/PPARγ) by tail vein also did not develop fatty liver, whereas mice with MED1 (MED1fl/fl) fed a high-fat diet or injected with Ad/PPARγ developed severe hepatic steatosis. Gene expression profiling and northern blot analyses of Ad/PPARγ-injected mouse livers showed impaired induction in MED1δLiv mouse liver of adipogenic markers, such as aP2, adipsin, adiponectin, and lipid droplet-associated genes, including caveolin-1, CideA, S3-12, and others. These adipocyte-specific and lipogenesis-related genes are strongly induced in MED1fl/fl mouse liver in response to Ad/PPARγ. Re-expression of MED1 using adenovirally-driven MED1 (Ad/MED1) in MED1δLiv mouse liver restored PPARγ-stimulated hepatic adipogenic response. These studies also demonstrate that disruption of genes encoding other coactivators such as SRC-1, PRIC285, PRIP, and PIMT had no effect on hepatic adipogenesis induced by PPARγ overexpression. Conclusion: We conclude that transcription coactivator MED1 is required for high-fat diet-induced and PPARγ-stimulated fatty liver development, which suggests that MED1 may be considered a potential therapeutic target for hepatic steatosis. (HEPATOLOGY 2011;)
Growth Suppression of Lung Cancer Cells by Targeting Cyclic AMP Response Element-Binding Protein
Authors: Sita Aggarwal, Seung-Wook Kim, Seung-Hee Ryu, Wen-Cheng Chung, Ja Seok Koo
Journal: Cancer Research (2008)

Genes regulated by cyclic AMP-response element-binding protein (CREB) have been reported to suppress apoptosis, induce cell proliferation, and mediate inflammation and tumor metastasis. However, it is not clear whether CREB is critically involved in lung carcinogenesis. We found that non-small cell lung cancer (NSCLC) cell lines exhibited elevated constitutive activity in CREB, in its immediate upstream kinases (ribosomal s6 kinase and extracellular signal kinase), and in the CREB-regulated cell survival proteins Bcl-2 and Bcl-xL. We hypothesized that constitutively active CREB is important to lung cancer cell growth and survival and therefore could be a potential therapeutic target for NSCLC. Ectopic expression of dominant repressor CREB and transfection with small interfering RNA against CREB suppressed the growth and survival of NSCLC cells and induced apoptotic cell death. Furthermore, treating H1734 NSCLC cells with an inhibitor of the CREB signaling pathway Ro-31-8220 inhibited CREB activation by blocking the activity of extracellular signal kinase and ribosomal s6 kinase, arrested the cell cycle at the G(2)-M phase, and subsequently induced apoptosis with the suppression of Bcl-2 and Bcl-xL expression. Ro-31-8220 suppressed both the anchorage-dependent and independent growth of NSCLC cells, but its cytotoxic effect was much less prominent in normal bronchial epithelial cells. Our results indicate that active CREB plays an important role in NSCLC cell growth and survival. Thus, agents that suppress CREB activation could have potential therapeutic value for NSCLC treatment.
Application of interphase cytogenetics to monitor bone marrow transplants
Authors: Vickie Vrazas, Lisa M. Ooms, Christina Rudduck, Jeffrey Szer, Lynda J. Campbell, O. Margaret Garson
Journal: American Journal of Hematology (1995)

Abstract Chromosomal in situ hybridization (ISH) has extended the scope of cytogenetic analysis to nondividing cells by the use of chromosome‐specific probes detected by nonisotopic techniques. This provides a rapid and sensitive method for identifying chromosomes in interphase cells, and is useful in gauging engraftment following bone marrow transplantation, particularly when the number of cells obtained is minimal. We have performed ISH using a Y‐heterochromatin‐specific probe to monitor patients with malignant hematological disease who have received a sex‐mismatched transplant. The results have been compared with those obtained from concurrently performed standard cytogenetic analysis. Host cells were detected by interphase cytogenetics in all patients posttransplant, at times varying from 28‐1,825 days, whereas routine analysis detected host cells in only 4 patients, 3 of whom were found to be in relapse. The significance of the persistence of host cells is unknown, but it does not appear to indicate impending relapse. © 1995 Wiley‐Liss, Inc.
Health inequalities and New Labour: how the promises compare with real progress
Authors: Mary Shaw, George Davey Smith, Danny Dorling
Journal: BMJ (2005)

Inequalities in health between rich and poor areas of Britain widened in the 1980s and 1990s, and the current government has repeatedly expressed its intention to reduce these inequalities. In this article, however, the authors report that inequalities in life expectancy have continued to widen, alongside widening inequalities in income and wealth, and argue that more potent and redistributive policies are needed
Pulmonary alveolar microlithiasis with involvement of the sympathetic nervous system and gonads
Authors: T. Coetzee
Journal: Thorax (1970)

Pulmonary alveolar microlithiasis is a relatively rare disease, of obscure aetiology, manifested by the presence of intra-alveolar laminated concretions distributed diffusely throughout the lungs. In all the recorded cases disease has been limited to the lungs and similar lesions have not been observed in other organs or tissues. The findings in a patient in whom lesions identical to those in the lungs were confirmed in the lumbar sympathetic chain and suspected to be present in the testes are recorded.
Pathological Analysis of Local Delivery of Paclitaxel Via a Polymer-Coated Stent
Authors: Andrew Farb, Phillip F. Heller, Sweta Shroff, Linda Cheng, Frank D. Kolodgie, Andrew J. Carter, Douglas S. Scott, Jeffrey Froehlich, Renu Virmani
Journal: Circulation (2001)

Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis. Early and late intimal growth and local vascular pathological changes associated with paclitaxel delivered via stents have not been fully explored.Localized drug delivery was accomplished with balloon-expandable stainless steel stents coated with a cross-linked biodegradable polymer, chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel. CSG-coated stents with paclitaxel (42.0, 20.2, 8.6, or 1.5 microgram of paclitaxel per stent), CSG-coated stents without paclitaxel, and uncoated stents (without paclitaxel or CSG) were deployed in the iliac arteries of New Zealand White rabbits, which were killed 28 days after implant. Mean neointimal thickness at stent strut sites was reduced 49% (P<0.0003) and 36% (P<0.007) with stents containing 42.0 and 20.2 microgram of paclitaxel per stent, respectively, versus CSG-coated stents without paclitaxel. However, histological findings suggested incomplete healing in the higher-dose (42.0 and 20.2 microgram) paclitaxel-containing stents consisting of persistent intimal fibrin deposition, intraintimal hemorrhage, and increased intimal and adventitial inflammation. Stents coated with CSG alone (without paclitaxel) had similar neointimal growth as uncoated stents. In a separate group of rabbits killed at 90 days, neointimal growth was no longer suppressed by CSG-coated stents containing 42.0 or 21.0 microgram of paclitaxelCSG coating appears to be a promising medium for localized drug delivery. Paclitaxel polymer-coated stents reduce neointima formation but are associated with evidence of incomplete healing at 28 days. However, neointimal suppression was not maintained at 90 days.
Liver histology in patients receiving low dose pulse methotrexate for the treatment of rheumatoid arthritis.
Authors: R.F Willkens, P.A Leonard, D.O Clegg, K.G Tolman, J.R Ward, C.R Marks, M.L Greene, G.J Roth, C.G Jackson, G.W Cannon
Journal: Annals of the Rheumatic Diseases (1990)

The liver histology of 52 patients treated with intermittent low dose pulse methotrexate for rheumatoid arthritis was evaluated using a modification of the Roenigk grading system. Patients studied had had an average of 3.2 years of treatment or had received 1.7 g methotrexate. No patient had cirrhosis; 15 (29%) patients had evidence of mild fibrosis. Histological abnormalities were not predicted by liver function test changes, with the exception that hypoalbuminaemia occurred in 60% of those with grade IV (modified criteria) findings. The need for liver biopsy in patients with rheumatoid arthritis treated with methotrexate before two years or 1500 mg of treatment has not been established. Whether serial liver biopsies will be needed beyond this time has yet to be determined.
Antioxidant consumption and repletion kinetics in nasal lavage fluid following exposure of healthy human volunteers to ozone
Authors: IS Mudway, A Blomberg, AJ Frew, ST Holgate, T Sandstrom, FJ Kelly
Journal: European Respiratory Journal (1999)

To obtain information on the real-time events occurring within human respiratory tract lining fluids (RTLFs) during ozone exposure, sequential nasal lavage was performed on 13 human volunteers exposed on separate occasions to 0.2 parts per million O3 and filtered air (2-h exposures, with intermittent exercise). Nasal lavage was performed and blood samples obtained at four time points throughout each exposure: pre-exposure (Pre-E), 1 h into exposure (1h-E), immediately post-exposure (0h-PE) and 1 h post-exposure (1h-PE). Endobronchial mucosal biopsies were obtained at 1.5 h-post exposure (1.5h-PE). Nasal RTLF neutrophilia was not apparent during, or 1.5 h after, 03 exposure. Furthermore, activation of the pre-existing neutrophil population did not occur. Airway permeability was not altered by this 03 exposure regimen. Sequential lavage resulted in significant washout of RTLF ascorbic acid, reduced glutathione, extracellular superoxide dismutase and myeloperoxidase at 1h-E, 0h-PE and 1.5h-PE relative to baseline Pre-E values. In contrast, RTLF uric acid (UA), total protein and albumin concentrations did not display washout kinetics. Of the antioxidants examined, only UA was clearly depleted by 03, concentrations, falling by 6.22 micromol x L(-1) at 1h-E, compared with 1.61 micromol x L(-1) (p&lt;0.01) during control air exposure. The establishment of a new pseudo-steady-state concentration of RTLF UA (70% of Pre-E values) during the second hour of O3 exposure was coincident with a small but significant increase in plasma UA concentration (19.27 (O3) versus 1.95 micromol x L(-1) (air), p&lt;0.05). These data demonstrate that inhalation of 0.2 parts per million 03 results in the depletion of nasal respiratory tract lining fluid uric acid and that this regional loss of uric acid leads to a small increase in plasma uric acid concentration. Whilst the reaction of uric acid with inspired 03 may confer protection locally, the role of upper airway uric acid as a sink for inhaled O3 is not supported by these findings.
NADPH Oxidase 4 Promotes Endothelial Angiogenesis Through Endothelial Nitric Oxide Synthase Activation
Authors: Siobhan M. Craige, Kai Chen, Yongmei Pei, Chunying Li, Xiaoyun Huang, Christine Chen;, Rei Shibata, Kaori Sato, Kenneth Walsh, John F. Keaney
Journal: Circulation (2011)

Background— Reactive oxygen species serve signaling functions in the vasculature, and hypoxia has been associated with increased reactive oxygen species production. NADPH oxidase 4 (Nox4) is a reactive oxygen species–producing enzyme that is highly expressed in the endothelium, yet its specific role is unknown. We sought to determine the role of Nox4 in the endothelial response to hypoxia. Methods and Results— Hypoxia induced Nox4 expression both in vitro and in vivo and overexpression of Nox4 was sufficient to promote endothelial proliferation, migration, and tube formation. To determine the in vivo relevance of our observations, we generated transgenic mice with endothelial-specific Nox4 overexpression using the vascular endothelial cadherin promoter (VECad-Nox4 mice). In vivo, the VECad-Nox4 mice had accelerated recovery from hindlimb ischemia and enhanced aortic capillary sprouting. Because endothelial nitric oxide synthase (eNOS) is involved in endothelial angiogenic responses and eNOS is activated by reactive oxygen species, we probed the effect of Nox4 on eNOS. In cultured endothelial cells overexpressing Nox4, we observed a significant increase in eNOS protein expression and activity. To causally address the link between eNOS and Nox4, we crossed our transgenic Nox4 mice with eNOS −/− mice. Aortas from these mice did not demonstrate enhanced aortic sprouting, and VECad-Nox4 mice on the eNOS −/− background did not demonstrate enhanced recovery from hindlimb ischemia. Conclusions— Collectively, we demonstrate that augmented endothelial Nox4 expression promotes angiogenesis and recovery from hypoxia in an eNOS-dependent manner.
Statins inhibit the antirheumatic effects of rituximab in rheumatoid arthritis: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry
Authors: E. E. A. Arts, T. L. Jansen, A. D. Broeder, H. E. Vonkeman, E. Dutmer, M. A. F. J. Van de Laar, P. L. C. M. Van Riel, J. Fransen
Journal: Annals of the Rheumatic Diseases (2010)

Rituximab (RTX) is used for the treatment of lymphomas and rheumatoid arthritis (RA), achieving its beneficial effect through B cell depletion.1 2 Recently it has been suggested that the effect of RTX may be inhibited by the concomitant use of statins.3,–,5 B cell depletion is achieved through apoptosis of B cells induced by hypercrosslinking of CD20 molecules with RTX. This process depends on the presence and integrity of lipid rafts in the cell membrane.3 6 7 In vitro, Winiarska et al showed that cholesterol depletion reduces apoptosis by RTX, inhibiting B cell depletion.3 However, two clinical studies that investigated concomitant statin use in patients with lymphoma reported no diminished effect on patient survival.8 9 These patients …