tbuckley/cabot-search huggingface dataset:
Peroxisome Proliferator–activated Receptors α and γ Down-regulate Allergic Inflammation and Eosinophil Activation
Authors: Gaetane Woerly, Kohei Honda, Marc Loyens, Jean-Paul Papin, Johan Auwerx, Bart Staels, Monique Capron, David Dombrowicz
Journal: The Journal of Experimental Medicine (2003)

Allergic asthma is characterized by airway hyperresponsiveness, eosinophilia, and mucus accumulation and is associated with increased IgE concentrations. We demonstrate here that peroxisome proliferator–activated receptors (PPARs), PPAR-α and PPAR-γ, which have been shown recently to be involved in the regulation of various cell types within the immune system, decrease antigen-induced airway hyperresponsiveness, lung inflammation, eosinophilia, cytokine production, and GATA-3 expression as well as serum levels of antigen-specific IgE in a murine model of human asthma. In addition, we demonstrate that PPAR-α and -γ are expressed in eosinophils and their activation inhibits in vitro chemotaxis and antibody-dependent cellular cytotoxicity. Thus, PPAR-α and -γ (co)agonists might be of therapeutic interest for the regulation of allergic or inflammatory reactions by targeting both regulatory and effector cells involved in the immune response.
OSAS and non-restorative sleep due to the interface
Authors: Michael Westhoff, Patric Litterst
Journal: European Respiratory Journal (2014)

Introduction

There are only few data about the influence of interfaces on restorative sleep and CPAP levels in sleep apnea. Because of repeated observations of non-restorative sleep under oro-nasal masks in spite of normal AHI and of obstructive hypopneas/apneas when using oro-nasal masks, with normalisation of AHI under nasal masks we studied such events from 11/2011 to 5/2013.

Results

56 patients (3 [female]: 63.7 ± 5.2 J; BMI: 38.9 ± 10.4 kg/m2 ; 53 [male]: 63.7 ± 13.5 J; BMI 31.6 ± 5.6 kg/m2) with OSAS (n = 46) and non-restorative sleep with normal AHI (n = 10) under oro-nasal masks were included. Main complaints were daytime sleepiness, uncomfortable mask-pressure, intolerance of CPAP.

Switching to nasal masks resulted in a reduction of CPAP-levels from 9.8 ± 2.3 cm H2O to 7.2 ± 1.8 cm H20 (p < 0.001), normalization of AHI (27.5 ± 15.5/h to 6.9 ± 5.8/h [p < 0.001]) and arousal-index (p < 0.001). Simultaneously this led to an increase of the minimal SaO2 from 81.6 % to 87.3 % (p < 0.001), of slow-wave- and REM-sleep (p < 0.05). The improvement was even more obvious in patients with pathological AHI. In patients with normal AHI but discomforts under an oro-nasal masks the usage of nasal masks was associated with a significant reduction of CPAP pressures (3.6 cm H20 - p < 0.001).

Conclusion

For CPAP-therapy a nasal mask should be preferred, even if mouth breathing is reported. Oro-nasal masks can induce paradoxical obstructive events. Changing a nasal to an oro-nasal mask needs awareness of this and should not be done for no apparent reason. If necessary a further sleep study is warranted. Obstructive events or sleepiness under an oro-nasal mask should raise suspicion of an interface related problem.
Residence in a urban area close to a petrochemical complex and its impact on allergic respiratory diseases in Italian schoolchildren
Authors: Fabio Cibella, Giuseppina Cuttitta, Silvia Ruggieri, Gaspare Drago, Francesca D'Aniello, Mario Melis, Salvatore Bucchieri, Stefania La Grutta, Giovanni Viegi
Journal: European Respiratory Journal (2013)

Aim of the study was to evaluate the influence of living in a urban area close to a petrochemical complex on questionnaire-reported allergic respiratory diseases in children. Between March and December 2012 we evaluated 1,248 schoolchildren (628 M), aged 10-16 yrs, selected from all the junior high schools of Gela (GE, 77,000 inhabitants/637 evaluatet subjects), Mediterranean area of Southern Italy, and those of Niscemi (NI, 26,400/354), Mazzarino (MA, 11,800/133), and Butera (BU, 4,900/124), in rural areas respectively 15, 27, and 16 km far from GE. A petrochemical industry, operating since 1965, is located close to the Gela urban area. Parents fulfilled a respiratory questionnaire. Asthmatic bronchitis during the first 2 yrs of life was reported by 10.2% in GE, 8.2 in NI, 5.0 in MA, and 0.0 in BU (p=.033, chi2 test). Rhinitis in the last 12 months was reported by 28.5% in GE, 15.5 in NI, 19.2 in MA, and 16.7 in BU (p=.0002). Doctor diagnosed asthma (A) was reported by 10.1% in GE, 7.7 in NI, 4.4 in MA, and 2.7 in BU (p=.014). Use of drugs intended for asthma therapy in the last 12 months was reported by 6.9% in GE, 5.2 in NI, 0.8 in MA, and 1.0 in BU (p=.011). In a logistic model, when correcting for parental atopy, passive smoke exposure, mould/dampness at home, personal history for rhinitis, and socioeconomic status, children living in GE show a eightfold risk factor for A with respect to those living in BU (OR 8.2, IC 1.1-61.3, p=.04, p for trend .02). In conclusion, children living in a highly polluted area are at higher risk for developing allergic respiratory diseases.  Funded by Operational Cross-border Program Italy-Malta 2007-2013.
Effect of closure of live poultry markets on poultry-to-person transmission of avian influenza A H7N9 virus: an ecological study
Authors: Hongjie Yu, Joseph T Wu, Benjamin J Cowling, Qiaohong Liao, Vicky J Fang, Sheng Zhou, Peng Wu, Hang Zhou, Eric H Y Lau, Danhuai Guo, Michael Y Ni, Zhibin Peng, Luzhao Feng, Hui Jiang, Huiming Luo, Qun Li, Zijian Feng, Yu Wang, Weizhong Yang, Gabriel M Leung
Journal: The Lancet (2013)
Can open-source R&amp;D reinvigorate drug research?
Authors: Bernard Munos
Journal: Nature Reviews Drug Discovery (2006)

The open-source software movement has successfully pioneered several strategies that might also be applicable in drug discovery and development. Munos considers the challenges involved, and proposes a model to harness the potential of open-source drug R&D. The low number of novel therapeutics approved by the US FDA in recent years continues to cause great concern about productivity and declining innovation. Can open-source drug research and development, using principles pioneered by the highly successful open-source software movement, help revive the industry?
BAFF controls B cell metabolic fitness through a PKCβ- and Akt-dependent mechanism
Authors: Alina Patke, Ingrid Mecklenbräuker, Hediye Erdjument-Bromage, Paul Tempst, Alexander Tarakhovsky
Journal: The Journal of Experimental Medicine (2006)

B cell life depends critically on the cytokine B cell–activating factor of the tumor necrosis factor family (BAFF). Lack of BAFF signaling leads to B cell death and immunodeficiency. Excessive BAFF signaling promotes lupus-like autoimmunity. Despite the great importance of BAFF to B cell biology, its signaling mechanism is not well characterized. We show that BAFF initiates signaling and transcriptional programs, which support B cell survival, metabolic fitness, and readiness for antigen-induced proliferation. We further identify a BAFF-specific protein kinase C β–Akt signaling axis, which provides a connection between BAFF and generic growth factor–induced cellular responses.
Dietary and hormonal regulation of aldolase B gene expression.
Authors: A Munnich, C Besmond, S Darquy, G Reach, S Vaulont, J C Dreyfus, A Kahn
Journal: Journal of Clinical Investigation (1985)

Aldolase B is an enzyme of the glycolytic pathway whose activity and mRNA levels in the liver fluctuate according to dietary status. Both the enzyme activity and the mRNA concentration decline during fasting and increase four- to eightfold upon refeeding of a carbohydrate-rich diet. The mechanism, however, of the mRNA induction remains unknown. To elucidate the mechanisms that regulate this induction responsive to dietary stimuli, we have studied the roles of hormones and glycolytic substrates on aldolase B gene expression in three tissues that synthesize the enzyme. Using a cDNA probe complementary to rat aldolase B mRNA, we determined the amount of cytoplasmic RNAs in the liver, kidney, and small intestine of normal, adrenalectomized, thyroidectomized, diabetic, and glucagon- or cAMP-treated animals refed either a fructose-rich or a maltose-rich diet. The in vivo hormonal control of gene expression was found to be very different in the three organs tested. In the liver, cortisone and thyroid hormones were required for the induction of the specific mRNA by carbohydrates, while in the kidney none of the hormonal modifications tested altered the level of mRNA induction. In the liver, but not in the kidney, diabetes and glucagon administration abolished the induction of aldolase B mRNAs in animals refed the maltose-rich diets. In the small intestine, only diabetes and thyroidectomy affected the gene expression. Finally, no induction occurred when normal fasted rats were given any of the hormones. Thus, the in vivo hormonal control of liver aldolase B gene expression differs significantly from that of kidney and small intestine. In the liver, the mRNA induction requires the presence of dietary carbohydrates, of permissive hormones, and the cessation of glucagon release, while in the kidney, the induction of the mRNAs by fructose occurs regardless of the hormonal status of the animals. The hormonal control of aldolase B mRNA levels in the small intestine is intermediate.
Integrin α2 Mediates Selective Metastasis to the Liver
Authors: Kiyoshi Yoshimura, Kristen F. Meckel, Lindsay S. Laird, Christina Y. Chia, Jang-June Park, Kelly L. Olino, Ryouichi Tsunedomi, Toshio Harada, Norio Iizuka, Shoichi Hazama, Yukihiko Kato, Jesse W. Keller, John M. Thompson, Fumin Chang, Lewis H. Romer, Ajay Jain, Christine Iacobuzio-Donahue, Masaaki Oka, Drew M. Pardoll, Richard D. Schulick
Journal: Cancer Research (2009)

Abstract Cancers display distinct patterns of organ-specific metastasis. Comparative analysis of a broad array of cell membrane molecules on a liver-metastasizing subline of B16 melanoma versus the parental B16-F0 revealed unique up-regulation of integrin α2. The direct role of integrin α2 in hepatic metastasis was shown by comparison of high versus low-expressing populations, antibody blockade, and ectopic expression. Integrin α2–mediated binding to collagen type IV (highly exposed in the liver sinusoids) and collagen type IV–dependent activation of focal adhesion kinase are both known to be important in the metastatic process. Analysis of primary colorectal cancers as well as coexisting liver and lung metastases from individual patients suggests that integrin α2 expression contributes to liver metastasis in human colorectal cancer. These findings define integrin α2 as a molecule conferring selective potential for formation of hepatic metastasis, as well as a possible target to prevent their formation. [Cancer Res 2009;69(18):7320–8]
Observations ON THE NATURE AND SYMPTOMS OF CARDIAC INFECTION IN CHILDHOOD
Authors: F. J. Poynton
Journal: BMJ (1918)

THE MITRAL VALVE.THE commencenment of rlheuinmatic endocarditis of the mitral valve is botind up witlh the early acute dilatation of the heart, and the symptoms are very few.There need be no pain, and fever is not essential.An increase in the rate of tlle pulse, sonme breatlhlessness and possibly palpitation, if thie chiild is not confined to bed, are suspi-cious, but these are duie to the myocardial weakness rather than to the valvular disease.We lhave only to picture the minute lesions that constitutp an early endocarditis to realize this lack of symptoms, and it is amply borne-out clinically by tlle ease with whiclh a primary cardiac rheumatism can be overlooked.I am nevertheless opposed to any attempt to iinimize the importance of' valvular disease, for though, no doubt, in former years overmiiuclh attenltion was paid to it as the agent in cardiac failure, wve calnnot neglect its
The Treatment of Cancer by Injections of Nitric Acid
Authors: J. H. Bennett
Journal: BMJ (1866)

<h3>Summary</h3> Viruses often encode proteins that mimic host proteins in order to facilitate infection. Little work has been done to understand the potential mimicry of the SARS-CoV-2, SARS-CoV, and MERS-CoV spike proteins, particularly the receptor-binding motifs, which could be important in determining tropism of the virus. Here, we use structural bioinformatics software to characterize potential mimicry of the three coronavirus spike protein receptor-binding motifs. We utilize sequence-independent alignment tools to compare structurally known or predicted three-dimensional protein models with the receptor-binding motifs and verify potential mimicry with protein docking simulations. Both human and non-human proteins were found to be similar to all three receptor-binding motifs. Similarity to human proteins may reveal which pathways the spike protein is co-opting, while analogous non-human proteins may indicate shared host interaction partners and overlapping antibody cross-reactivity. These findings can help guide experimental efforts to further understand potential interactions between human and coronavirus proteins. <h3>Highlights</h3> Potential coronavirus spike protein mimicry revealed by structural comparison Human and non-human protein potential interactions with virus identified Predicted structural mimicry corroborated by protein-protein docking Epitope-based alignments may help guide vaccine efforts <h3>Graphical abstract</h3>
Reply to M. Rosman et al
Authors: Mitch Dowsett, Silvia Pineda, Jack Cuzick
Journal: Journal of Clinical Oncology (2010)

We welcome the opportunity to respond to the correspondence from Rosman et al in reference to our article assessing the performance of the Oncotype DX Recurrence Score (RS) in patients from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial. As requested, we have examined our data for evidence of the performance of the RS in patients with human epidermal growth factor receptor 2 (HER2) –negative disease. In our earlier analysis, we fitted a multivariate Cox proportional hazards model in a total of 1,178 patients (872 with node-negative [N0] disease; 306 with node-positive [N ] disease). In this set, the hazard ratios (HRs) for a 50-point increment in the RS element of the model were 5.25 (95% CI, 2.84 to 9.78; 2 22.7; P .001) for patients with N0 disease and 3.47 (95% CI, 1.64 to 7.38; 2 9.4; P .002) for patients with N disease. In our new analyses, the patient numbers are reduced by 18 to 1,160 (855 N0; 305 N ) because of missing HER2 status. The HRs for the RS element are nearly identical to the old values, being 5.27 and 3.38, respectively. There were 1,038 HER2-negative tumors in 764 patients with N0 disease and 274 patients with N disease. HRs for the RS element of the model for these patients are 6.08 (95% CI, 2.22 to 16.66; 2 10.8; P .001) for patients with N0 disease and 5.18 (95% CI, 1.64 to 16.37; 2 7.3; P .007) for patients with N disease. Thus the estimated HRs for the RS are somewhat larger for the HER2-negative group, and although the statistical significance of the effect of adding RS to the clinicopathologic elements of the model is less than for the whole population because of fewer events, the effect remains highly significant. The proportions of patients in the RS low-, intermediate-, and high-risk groups were 57%, 28%, and 15%, respectively, for the combined HER2 negative and HER2 positive. The respective figures for the HER2-negative population were 62%, 28%, and 10%. These analyses indicate that the RS adds substantial information on the risk of distant recurrence when restricted to the HER2negative population.
Reply to M.R. Smith et al
Authors: Douglas G. McNeel
Journal: Journal of Clinical Oncology (2009)

raise a question regarding the evaluation of changes in prostate-specific antigen (PSA) kinetics in our recent report of a phase I clinical trial of a DNA vaccine encoding prostatic acid phosphatase. 2They cite previous phase II clinical trials showing changes in PSA doubling time (PSA DT) in patients enrolled onto placebo control arms.They conclude that "post-treatment changes in PSA DT following vaccine treatment do not provide evidence of biologic activity.Additional studies are necessary to assess the relationship between PSA kinetics and clinical outcomes and to evaluate the utility of post-treatment PSA DT or PSA velocity in the development of new drugs." 1(pe58) We agree that the use of changes in PSA DT is not validated as an end point associated with known impact on clinical outcomes.We acknowledged this issue in the article, wherein we stated that "it should be highlighted that the clinical significance of changes in PSA DT from any treatment remains unknown and awaits the results of prospective randomized trials to determine whether changes are associated with changes in radiographic disease progression." 2(p4052) We would further highlight that our study was a phase I trial in which the primary end points were safety and immunologic effect in eliciting prostatic acid phosphatasespecific CD8ϩ T cells.Consequently, our specified measure of biologic effect was an immunologic end point and not a change in PSA kinetics.We believe that our immunologic analyses do provide evidence of biologic activity.However, because PSA is the only measure of disease in the setting of biochemical recurrence of prostate cancer, it is important to collect and report these data, as has been recommended by a consensus panel on this topic. 3As such, our plan moving forward is to conduct a randomized phase II clinical trial with this DNA vaccine, using time to radiographic progression as the primary clinical end point.
Hepatitis B: absence of transmission by gastrointestinal endoscopy.
Authors: D B McClelland, C J Burrell, R W Tonkin, R C Heading
Journal: BMJ (1978)

23 peripheral blood, 4-6 -of his lymphocytes being Downey cells.Five months after the start of his illness he had a CF antibody titre of 40 and an IF titre of IgM antibodies of 8 against CMV.Unfortunately bacterial contamination spoilt our attempt to isolate CMV from his urine. CommentCMV can be isolated from urine during and sometimes many months after a clinical illness associated with this virus.For technical reasons we could not establish whether our patient's husband was a CMV excretor, but CMV was isolated from his wife's urine during her illness and both had serum antibodies against CMV.It seems clinically highly probable, though it was not virologically proved, that the man's illness was associated with a CMV infection.He fell ill within the incubation period for a post-transfusion CMV infection3 and his clinical picture resembled that which appears in association with CMV infection.i-3Our patient became ill 15 weeks after her husband had recovered clinically, but only four weeks after his "haematological recovery."The virological findings showed that she had a current CMV infection, evidently a primary one,5 during the period she was ill with a mononucleosis-like syndrome of septic type.The couple lived alone in their house.A spread of CMV infection from the husband to his wife seems very likely, though we cannot explain why the virus transmission from husband to wife did not occur earlier.This case history shows that clinicians must be aware of the possibility of a spread of CMV from a patient who has undergone heart surgery or renal transplantation to other members of the family.Even if most of the primary CMV infections are asymptomatic, a few may cause a longlasting fever.
Quality of Life of Children After Repair of Transposition of the Great Arteries
Authors: Erin L. Culbert, David A. Ashburn, Geraldine Cullen-Dean, Jay A. Joseph, William G. Williams, Eugene H. Blackstone, Brian W. McCrindle
Journal: Circulation (2003)

We sought to assess quality of life of children with transposition of the great arteries (TGA) enrolled during transition in management strategy from atrial to arterial switch operation.Neonates enrolled by the Congenital Heart Surgeons Society in a prospective study of TGA between 1985 and 1989 were eligible. A Child Health Questionnaire was sent for completion by the child between February and June 2000. Data were compared with published normative values. Child Health Questionnaires were completed by 306 of 708 survivors at a mean age of 13+/-1 years. Diagnosis included TGA (n=202, 66%), TGA/ventricular septal defect (VSD) (n=84, 27%), and TGA/VSD/pulmonary stenosis (n=20, 7%). Repair type was arterial switch (n=189, 62%), atrial switch (n=105, 34%; Senning=58, Mustard=47), or Rastelli (n=12, 4%). Children with TGA scored significantly higher than published norms in all categories except self-esteem. TGA/VSD/pulmonary stenosis was associated with lower scores than TGA and TGA/VSD in physical functioning (P=0.002), general health perceptions (P=0.012), and mental health (P=0.048). Arterial repair was associated with higher scores than atrial or Rastelli repair in physical functioning (P<0.001), pain (P=0.004), mental health (P=0.019), self-esteem (P=0.004), and general health perceptions (P<0.001). By multivariable analyses, the most common independent factors impacting scores were repair type, perfusion parameters, and gender.Quality of life and health status as perceived by children 11 to 15 years after TGA repair is excellent when compared with published normative data and is better after arterial switch operation than after atrial repair.
Asthma, allergy, and atopy in three south-east Asian populations.
Authors: R Leung, P Ho
Journal: Thorax (1994)

Whilst many recent reports have suggested a rise in the prevalence of asthma and allergic disease in Western countries, little is known about the epidemiology of these common conditions in south-east Asia. This study compared the prevalence of asthma and allergic disease amongst secondary school students in three south-east Asian populations--Hong Kong, Kota Kinabalu in Malaysia, and San Bu in China--and investigated the associations with atopy and family history.Secondary school students were given standard questionnaires on respiratory and allergic symptoms for completion by parents with response rates of 89.2% in Hong Kong (611 male, 451 female; mean (SD) age = 13.9 (1.8 years), 87.6% in Kota Kinabalu (134 male, 275 female; 15.5 (2.1) years), and 98.6% in San Bu (492 male, 245 female; 16.4 (1.8) years). Skin tests were performed in a subsample of students to determine atopic status.The respective prevalence (and 95% CI) for hayfever, eczema, and wheeze or asthma were 15.7% (13.5, 17.9), 20.1% (17.7, 22.5), 11.6% (9.3, 13.9) in Hong Kong, 11.2% (8.2, 14.3), 7.6% (5.0, 10.1), 8.2% (5.5, 10.9) in Kota Kinabalu, and 2.1% (1.2, 3.1), 7.2% (5.4, 9.1), 1.9% (0.7, 3.1) in San Bu. Atopy was common and was present in 49.0-63.9% of subjects in the three populations. Dust mite and cockroach were the commonest allergens that gave positive reactions in 42.8-60.5% and 25.7-35.9% of students respectively. A higher proportion of students in Hong Kong had severe degree of reactivity on skin test than the other two populations. Family history was associated with asthma and allergic symptoms in the three populations conferring a 3-80-fold increase in risk to family members and was a stronger predictor for asthma and allergy than atopy.Prevalence of asthma and allergic disease is low compared with Western countries, but considerable differences exist between the three south-east Asian populations despite similar rates of atopy. Asthma and allergic disease are more strongly associated with family history than atopy, which suggests that genetic and environmental factors common to the family, other than aeroallergen sensitisation, are important in the pathogenesis of asthma and allergy in the region.
Evaluating potential for whole-genome studies in Kosrae, an isolated population in Micronesia
Authors: Penelope E Bonnen, Itsik Pe'er, Robert M Plenge, Jackie Salit, Jennifer K Lowe, Michael H Shapero, Richard P Lifton, Jan L Breslow, Mark J Daly, David E Reich, Keith W Jones, Markus Stoffel, David Altshuler, Jeffrey M Friedman
Journal: Nature Genetics (2006)