tbuckley/cabot-search huggingface dataset:
Impact of noise on hearing in the military
Authors: Jenica Yong, De-Yun Wang
Journal: Military Medical Research (2015)

Hearing plays a vital role in the performance of a soldier and is important for speech processing. Noise-induced hearing loss is a significant impairment in the military and can affect combat performance. Military personnel are constantly exposed to high levels of noise and it is not surprising that noise induced hearing loss and tinnitus remain the second most prevalent service-connected disabilities. Much of the noise experienced by military personnel exceeds that of maximum protection achievable with double hearing protection. Unfortunately, unlike civilian personnel, military personnel have little option but to remain in noisy environments in order to complete specific tasks and missions. Use of hearing protection devices and follow-up audiological tests have become the mainstay of prevention of noise-induced hearing loss. This review focuses on sources of noise within the military, pathophysiology and management of patients with noise induced hearing loss.
Mice transgenic for a soluble form of murine CTLA-4 show enhanced expansion of antigen-specific CD4+ T cells and defective antibody production in vivo.
Authors: F Ronchese, B Hausmann, S Hubele, P Lane
Journal: The Journal of Experimental Medicine (1994)

CD4+ T cell responses were analyzed in transgenic mice expressing a soluble form of murine CTLA-4, mCTLA4-H gamma 1, which blocks the interaction of the T cell activation molecules CD28 and CTLA-4 with their costimulatory ligands. Consistent with previous reports (Linsley, P. S., P. M. Wallace, J. Johnson, M. G. Gibson, J. L. Greene, J. A. Ledbetter, C. Singh, and M. A. Tepper. 1992. Science (Wash. DC). 257:792), T cell-dependent antibody production was profoundly inhibited in mCTLA4-H gamma 1 transgenic mice immunized with a protein antigen. Surprisingly, however, transgenic mice could generate quantitatively and qualitatively normal primary T cell responses, as measured by limiting dilution assays and lymphokine production. In addition, in vivo expansion of antigen-specific T cells after secondary or tertiary immunization was enhanced in mCTLA4-H gamma 1 transgenics as compared with normal mice. Although unable to deliver cognate help to B cells in vivo, T cells from mCTLA4-H gamma 1 transgenic mice were not anergic as they could help B cells to produce specific antibodies when adoptively transferred into nude hosts. Taken together, these data suggest that the engagement of CD28 and/or CTLA-4 may not be required for the induction of T cell responses, as is currently understood, but rather for the expression of T cell effector function such as the delivery of T cell help to B cells.
Molecular Imaging of Death Receptor 5 Occupancy and Saturation Kinetics <i>In Vivo</i> by Humanized Monoclonal Antibody CS-1008
Authors: Ingrid J.G. Burvenich, Fook T. Lee, Glenn A. Cartwright, Graeme J. O'Keefe, Dahna Makris, Diana Cao, Sylvia Gong, Anderly C. Chueh, John M. Mariadason, Martin W. Brechbiel, Robert A. Beckman, Kosaku Fujiwara, Reinhard von Roemeling, Andrew M. Scott
Journal: Clinical Cancer Research (2013)

CS-1008 (tigatuzumab; phase I/II), an antihuman death receptor 5 (DR5) agonist, induces apoptosis and has cytotoxic activity against human cancer cell lines. This study reports on the preclinical validation of (111)In-labeled anti-DR5 humanized antibody CS-1008 as a diagnostic tool to study the DR5 occupancy in patients with cancer and establish dose ranges for receptor saturation kinetics in vivo.CS-1008 was radiolabeled and characterized for DR5 binding and labeling efficiency on TRAIL-sensitive DR5-positive colorectal cancer cells (COLO 205 and WiDr). Pharmacokinetic and biodistribution studies were conducted in BALB/c nu/nu mice bearing COLO 205, WiDr, or DR5-negative CT26 colon tumors. Planar gamma camera imaging and computerized tomography (CT) images were obtained to study receptor occupancy in vivo.Scatchard analysis showed high and specific binding affinity (Kd, 1.05 ± 0.12 nmol/L) of (111)In-labeled CS-1008. (111)In-labeled CS-1008 was specifically taken up in mice bearing COLO 205 and WiDr tumors with prolonged tumor retention (26.25 ± 2.85%ID/g vs. 12.20 ± 2.24 at 168 hours post injection; n = 5, SD), and uptake correlated both with DR5 expression on tumor cells and antitumor activity. DR5 saturation was shown in vivo via both biodistribution studies and planar gamma camera imaging/CT imaging of (111)In-labeled CS-1008. Saturation of DR5 corresponded to maximal in vivo antitumor efficacy.Imaging of DR5 receptor occupancy in vivo correlates with tumor concentration and in vivo efficacy, and is a novel molecular imaging technique that can be used to determine receptor occupancy and effective dose levels of DR5 agonist antibodies in the clinic.
A comprehensive bibliography database using a microcomputer
Authors: D W Bullimore
Journal: BMJ (1986)

overload is common to all such units (Price DJ, IEE Colloquium 1984).The most sophisticated system will fail in the absence of data entry.Most clinical and nursing staff dislike the usual QWERTY keyboard, the means of data entry favoured by computer systems.The APACHE scoring described by Knaus et al3 shows the APACHE II system as a 9 x 12 box table.We have used this table as an overlay for a pressure sensitive graphics pad.Data entry is by box ticking, allowing direct data acquisition by a microcomputer.This approach does not need a keyboard, uses existing technology, allows data entry by a familiar method, and provides a record of the data actually entered.Nurses (and doctors) did not train to become typists.
?8?1 Integrin expression in the rat carotid artery: involvement in smooth muscle cell migration and neointima formation
Authors: R ZARGHAM, G THIBAULT
Journal: Cardiovascular Research (2004)

Objective: Migration of vascular smooth muscle cells (VSMCs) from the tunica media to the intima is a key event in neointima formation after coronary artery angioplasty. The central dogma in VSMC migration is cell modulation from the contractile to the noncontractile phenotype. Increased α8β1 integrin expression, observed in situations where the majority of cells are in the contractile phenotype, led us to hypothesize that a decrease of α8β1 integrin may play an important role in the migratory state of VSMCs.
Treatment standards not commercial interests should drive commissioning, say surgeons
Authors: A. O'Dowd
Journal: BMJ (2011)

Any new non-NHS providers who are involved in healthcare provision under the government’s proposed health reforms should adhere to new commissioning standards, claims the Royal College of Surgeons.

In its response to the government’s ongoing NHS Future Forum listening exercise published on 23 May, the college sets out principles and standards that non-NHS providers would have to meet to equal the standard of current providers.

The standards touch on training, education, audit, research, measuring outcomes, and assessing the impact of any changes made.

Overall the college welcomes the drive …
Study familial hypertrophic cardiomyopathy using patient-specific induced pluripotent stem cells
Authors: Lu Han, Yang Li, Jason Tchao, Aaron D. Kaplan, Bo Lin, You Li, Jocelyn Mich-Basso, Agnieszka Lis, Narmeen Hassan, Barry London, Glenna C.L. Bett, Kimimasa Tobita, Randall L. Rasmusson, Lei Yang
Journal: Cardiovascular Research (2014)

Familial hypertrophic cardiomyopathy (HCM) is one the most common heart disorders, with gene mutations in the cardiac sarcomere. Studying HCM with patient-specific induced pluripotent stem-cell (iPSC)-derived cardiomyocytes (CMs) would benefit the understanding of HCM mechanism, as well as the development of personalized therapeutic strategies.To investigate the molecular mechanism underlying the abnormal CM functions in HCM, we derived iPSCs from an HCM patient with a single missense mutation (Arginine442Glycine) in the MYH7 gene. CMs were next enriched from HCM and healthy iPSCs, followed with whole transcriptome sequencing and pathway enrichment analysis. A widespread increase of genes responsible for 'Cell Proliferation' was observed in HCM iPSC-CMs when compared with control iPSC-CMs. Additionally, HCM iPSC-CMs exhibited disorganized sarcomeres and electrophysiological irregularities. Furthermore, disease phenotypes of HCM iPSC-CMs were attenuated with pharmaceutical treatments.Overall, this study explored the possible patient-specific and mutation-specific disease mechanism of HCM, and demonstrates the potential of using HCM iPSC-CMs for future development of therapeutic strategies. Additionally, the whole methodology established in this study could be utilized to study mechanisms of other human-inherited heart diseases.
LRP1 shedding in human brain: roles of ADAM10 and ADAM17
Authors: Qiang Liu, Juan Zhang, Hien Tran, Marcel M Verbeek, Karina Reiss, Steven Estus, Guojun Bu
Journal: Molecular Neurodegeneration (2009)

The low-density lipoprotein receptor-related protein 1 (LRP1) plays critical roles in lipid metabolism, cell survival, and the clearance of amyloid-beta (Abeta) peptide. Functional soluble LRP1 (sLRP1) has been detected in circulating human placenta; however, whether sLRP1 is also present in the central nervous system is unclear.Here we show that abundant sLRP1 capable of binding its ligands is present in human brain tissue and cerebral spinal fluid (CSF). Interestingly, the levels of sLRP1 in CSF are significantly increased in older individuals, suggesting that either LRP1 shedding is increased or sLRP1 clearance is decreased during aging. To examine potential effects of pathological ligands on LRP1 shedding, we treated MEF cells with Abeta peptide and found that LRP1 shedding was increased. ADAM10 and ADAM17 are key members of the ADAM family that process membrane-associated proteins including amyloid precursor protein and Notch. We found that LRP1 shedding was significantly decreased in MEF cells lacking ADAM10 and/or ADAM17. Furthermore, forced expression of ADAM10 increased LRP1 shedding, which was inhibited by ADAM-specific inhibitor TIMP-3.Our results demonstrate that LRP1 is shed by ADAM10 and ADAM17 and functional sLRP1 is abundantly present in human brain and CSF. Dysregulated LRP1 shedding during aging could alter its function and may contribute to the pathogenesis of AD.
Immunity and bacterial colonisation in bronchiectasis
Authors: Deborah Whitters, Robert Stockley
Journal: Thorax (2011)

<h3>Background</h3> Non-cystic fibrosis bronchiectasis is characterised by irreversibly dilated bronchi usually associated with chronic sputum production, bacterial colonisation of the lower respiratory tract, inflammation and frequent exacerbations. Irrespective of the underlying cause, this represents failure of the host defence to maintain sterility of the respiratory tract. <h3>Objective</h3> To review the interactions and associations of non-cystic fibrosis bronchiectasis with the inate and adaptive immune systems with particular emphasis on known failure of local defences established deficiencies of the adaptive immune system. In addition we wished to explore potential subtle changes in the host defence which can lead to bacterial colonisation together with bacterial factors that aid colonisation of the lower respiratory tract and impair antibiotic response. This latter concept is considered with particular reference to Pseudomonas aeruginosa, which is often found in the airway secretions of patients with non-cystic fibrosis bronchiectasis and may act as a model for other organisms. <h3>Methods</h3> An extensive literature review was undertaken to provide a comprehensive review of immunity and bacterial colonisation in non-cystic fibrosis bronchiectasis, with focus on in vitro studies examining bacterial factors which may facilitate colonisation together with potential implications for management. <h3>Conclusion</h3> These themes provide a review of the current understanding of non-cystic fibrosis bronchiectasis together with areas for future research and potential therapeutic strategies.
Perinatal risk factors for asthma in Finnish adolescent twins
Authors: M. Rasanen
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Previous studies have suggested that, in addition to genetic liability and environment in early childhood, intrauterine life also influences the risk for asthma beyond childhood. Low birth weight, prematurity, young maternal age, and maternal smoking have all shown an association with asthma. The effect of perinatal factors on the risk for asthma in relation to familial and social risk factors was studied in a nationwide population-based sample of adolescent twins. In addition to a distribution of birth characteristics among twins which differs from that of singletons, data on twins enable a distinction to be made between genetic and environmental sources of variation. <h3>METHODS</h3> Questionnaires were sent to five consecutive birth cohorts of Finnish 16 year old twins born in 1975–9 and to their parents (3065 families). The outcome measure was life time prevalence of doctor-diagnosed asthma in these adolescents. The association between asthma and potential risk factors was assessed by multiple logistic regression and discordant twin pair analysis. <h3>RESULTS</h3> Risk for asthma increased with increasing ponderal index (p for trend &lt;0.01) and decreasing maternal age (p for trend &lt;0.05). Among the 25% of twins with the highest ponderal index, the odds ratio for asthma was 1.82 (95% confidence interval 1.18 to 2.79) compared with those in the lowest 25%. Neither birth weight, gestational age, nor Apgar score was associated with asthma. When perinatal risk factors were combined with familial and social risk factors, ponderal index, maternal smoking, parental asthma, and sibship size were all significant independent determinants of asthma in these adolescents. <h3>CONCLUSIONS</h3> The risk for asthma in adolescent twins increases with increasing ponderal index when adjusted for familial and social factors.
Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum
Authors: L Senolt, D Housa, Z Vernerova, T Jirasek, R Svobodova, D Veigl, K Anderlova, U Muller-Ladner, K Pavelka, M Haluzik
Journal: Annals of the Rheumatic Diseases (2006)

Resistin is a newly identified adipocytokine which has demonstrated links between obesity and insulin resistance in rodents. In humans, proinflammatory properties of resistin are superior to its insulin resistance-inducing effects.To assess resistin expression in synovial tissues, serum and synovial fluid from patients with rheumatoid arthritis, osteoarthritis and spondylarthropathies (SpA), and to study its relationship with inflammatory status and rheumatoid arthritis disease activity.Resistin expression and localisation in synovial tissue was determined by immunohistochemistry and confocal microscopy. Serum and synovial fluid resistin, leptin, interleukin (IL)1beta, IL6, IL8, tumour necrosis factor alpha, and monocyte chemoattractant protein-1 levels were measured. The clinical activity of patients with rheumatoid arthritis was assessed according to the 28 joint count Disease Activity Score (DAS28).Resistin was detected in the synovium in both rheumatoid arthritis and osteoarthritis. Staining in the sublining layer was more intensive in patients with rheumatoid arthritis compared with those with osteoarthritis. In rheumatoid arthritis, macrophages (CD68), B lymphocytes (CD20) and plasma cells (CD138) but not T lymphocytes (CD3) showed colocalisation with resistin. Synovial fluid resistin was higher in patients with rheumatoid arthritis than in those with SpA or osteoarthritis (both p<0.001). In patients with rheumatoid arthritis and SpA, serum resistin levels were higher than those with osteoarthritis (p<0.01). Increased serum resistin in patients with rheumatoid arthritis correlated with both CRP (r=0.53, p<0.02), and DAS28 (r=0.44, p<0.05), but not with selected (adipo) cytokines.The upregulated resistin at local sites of inflammation and the link between serum resistin, inflammation and disease activity suggest a role for resistin in the pathogenesis of rheumatoid arthritis.
Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues.
Authors: J Xu-Amano, H Kiyono, R J Jackson, H F Staats, K Fujihashi, P D Burrows, C O Elson, S Pillai, J R McGhee
Journal: The Journal of Experimental Medicine (1993)

Antigen-specific B cell responses to mucosally delivered proteins are dependent upon CD4-positive T helper (Th) cells, and the frequency of Th1 and Th2 cell responses after oral immunization may determine the level and isotype of mucosal antibody responses. We have used a protein-based vaccine, tetanus toxoid (TT), together with the mucosal adjuvant cholera toxin (CT), for oral immunization of mice to study the nature of antigen-specific Th cell subsets induced in Peyer's patches (PP) of the gastrointestinal (GI) tract and in the spleen (SP) during peak antibody responses. Mice orally immunized with TT and CT responded with antigen-specific secretory immunoglobulin A (S-IgA) antibodies in the GI tract, and with both IgG and IgA antibody responses in serum. PP and SP CD4+ T cells from mice orally immunized with TT plus CT were cultured with antigen-coated latex microspheres for induction of proliferative responses and for enumeration of cytokine producing CD4+ T cells. Interestingly, both PP and SP CD4+ T cell cultures showed increased numbers of IL-4- and IL-5 (Th2-type)-producing, spot-forming cells (SFCs) after 21 d of immunization, while essentially no interferon-gamma (IFN-gamma) or IL-2 (Th1-type) SFCs were noted. Cytokine-specific Northern blots and RT-PCR also revealed that significant IL-4 and IL-5 mRNA levels, but not IFN-gamma or IL-2 mRNA, were present in CD4+ T cells isolated from antigen-stimulated cultures. However, systemic immunization with TT and CT induced antigen-specific IgG and IgM but not IgA antibodies in serum. Further, both IL-2 and IFN-gamma-producing Th1-type cells as well as IL-4- and IL-5-secreting Th2-type cells were generated in SP. Our results show that oral immunization with TT and the mucosal adjuvant CT selectively induced antigen-specific Th2-type responses which may represent the major helper cell phenotype involved in mucosal IgA responses in the GI tract.
Effect of Exacerbation on Quality of Life in Patients with Chronic Obstructive Pulmonary Disease
Authors: TERENCE A. R. SEEMUNGAL, GAVIN C. DONALDSON, ELIZABETH A. PAUL, JANINE C. BESTALL, DONALD J. JEFFRIES, JADWIGA A. WEDZICHA
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Exacerbations occur commonly in patients with moderate or severe chronic obstructive pulmonary disease (COPD) but factors affecting their severity and frequency or effects on quality of life are unknown. We measured daily peak expiratory flow rate (PEFR) and daily respiratory symptoms for 1 yr in 70 COPD patients (52 male, 18 female, mean age [ ± SD] 67.5 ± 8.3 yr, FEV1 1.06 ± 0.45 L, FVC 2.48 ± 0.82 L, FEV1/FVC 44 ± 15%, FEV1 reversibility 6.7 ± 9.1%, PaO2 8.8 ± 1.1 kPa). Quality of life was measured by the St. George's Respiratory Questionnaire (SGRQ). Exacerbations (E) were assessed at acute visit (reported exacerbation) or from diary card data each month (unreported exacerbation). In 61 (87%) patients there were 190 exacerbations (median 3; range, 1 to 8) of which 93 (51%) were reported. There were no differences in major symptoms (increase in dyspnea, sputum volume, or purulence) or physiological parameters between reported and unreported exacerbations. At exacerbation, median peak flow fell by an average of 6.6 L/min (p = 0.0003). Using the median number of exacerbations as the cutoff point, patients were classified as infrequent exacerbators (E = 0 to 2) or frequent exacerbators (E = 3 to 8). The SGRQ Total and component scores were significantly worse in the group that had frequent exacerbations: SGRQ Total score (mean difference = 14.8, p < 0.001), Symptoms (23.1, p < 0.001), Activities (12.2, p = 0.003), Impacts (13.9, p = 0.002). However there was no difference between frequent and infrequent exacerbators in the fall in peak flow at exacerbation. Factors predictive of frequent exacerbations were daily cough (p = 0.018), daily wheeze (p = 0.011), and daily cough and sputum (p = 0.009) and frequent exacerbations in the previous year (p = 0.001). These findings suggest that patient quality of life is related to COPD exacerbation frequency.
Benefit of steroid-free treatment compared to standard therapy (ST) in pulmonary sarcoidosis
Authors: Christian Grah, Conny Thieme, Rose Seiberth, Jochens Arne, Angela McCutcheon, Stefan Schreiber, Joachim Müller-Quernheim
Journal: European Respiratory Journal (2014)

Introduction: In a case series, Havelhoehe sarcoidosis protocol (HSP) was defined to find an alternative to ST. Objective: Steroid-free treatment with HSP was compared retrospectively with a cohort undergoing ST from the GenPhenReSa trial[1] as control group (CG). We suspected beneficial trends regarding lung function, chest-X-ray, and fatigue scale. Methods: N = 56. 1 cycle HSP:

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HSP





At least 2 cycles were given. We treated 3 sub-cohorts: 1: steroid naive patients indicated for ST 2: ST but recurring symptoms or repeated ST with relapse in treatment-free interval 3: sarcoidosis related B symptoms without indication for ST and extracted 3 reference cohorts from CG with ST. CG: n = 2271. Thereof, n = 456 met the following requirements: 4 years of follow up, undergoing ST, no lost data. Results: 

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Results





It was evaluated by chest-X-ray analysis and fatigue scale. It proved a connection (p=0,000029 Fisher's exact test), a linear trend (p=0,000018 Cochran-Armitage test), and is consistent to lung function. Conclusion: HSP appears to have significant effects compared to ST and should be investigated in a prospective study.

[1] Database of trial: „Genotype-Phenotype Relationship in Sarcoidosis“ - Characterisation of the genetic background of clinically distinct courses (phenotypes) of sarcoidosis to eventually test early therapeutic interventions and identify patients who would benefit from experimental therapy.