tbuckley/cabot-search huggingface dataset:
Endothelial Nitric Oxide Synthase Gene/Gender Interactions and the Renal Hemodynamic Response to Angiotensin II
Authors: Andrea Page, Heather Reich, Joyce Zhou, Vesta Lai, Daniel C Cattran, James W Scholey, Judith A Miller
Journal: Journal of the American Society of Nephrology (2005)

Endothelial function is dependent on the generation of nitric oxide (NO) by the enzyme endothelial NO synthase (eNOS). One functional coding polymorphism of the eNOS gene (G894-->T) is associated with reduced enzyme activity, increased coronary heart disease, and the development of end-stage renal failure. Because gender and renin-angiotensin system activation also play key roles in the development of renal and cardiovascular disease and because NO plays a role in the response to angiotensin II (AngII), it was hypothesized that the eNOS gene G894-->T polymorphism would be a determinant of the systemic and renal vascular response to AngII. Fifty young, healthy, normotensive individuals who were on a controlled sodium and protein diet for 1 wk underwent assessment of BP and renal hemodynamic function at baseline and during AngII infusion (4 ng/kg per min for 45 min). Participants were genotyped for the eNOS gene G894-->T polymorphism and then segregated into groups on the basis of gender and genotype (GG versus GT/TT). Baseline values for renal blood flow, effective renal plasma flow, and GFR were lower in men with the T allele compared with men who were homozygous for the G allele (P = 0.03), but the polymorphism was not associated with renal hemodynamic function in women. The BP responses to AngII were similar in men and women regardless of genotype. Both multivariate linear regression and analysis of covariance (ANCOVA) revealed a relationship between gender and genotype. Men with the GT/TT genotype exhibited a significantly greater decrease in GFR (P = 0.04) in response to AngII than did those with the GG genotype. This association was not observed in women. The eNOS gene G894-->T polymorphism is a determinant of both baseline renal hemodynamic function and the hemodynamic response to AngII in men but not in women.
Environmental micro-organisms and childhood asthma: the more the merrier?
Authors: K Srikanthan
Journal: Thorax (2011)

Epidemiological studies have shown that children who grow up on traditional farms are protected from atopic conditions, including asthma. However, how this protection arises is not clearly understood. It has been postulated that immunological responses to an increased microbial exposure in early childhood is important. This study investigates, specifically, whether it is the …
Drug industry pledge on access to trial data is met with scepticism
Authors: A. O'Dowd
Journal: BMJ (2013)

Promises of far greater transparency and access to clinical trial data set out in new drug industry-wide principles have been met with scepticism by clinicians and researchers.

Two of the largest trade bodies representing the pharmaceutical industry—the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA)—published joint principles for responsible clinical trial data sharing on 18 July.1

The European federation collectively speaks for 1900 companies, while the US association has 32 member organisations.

The principles, which come into effect from next January, promise that biopharmaceutical companies will dramatically increase the amount of information available to researchers, patients, and members of the public.

The principles have been agreed to by all of the two associations’ member organisations.

They say that all drug companies will set up independent “scientific review boards” (made up of scientists and healthcare professionals not employed by the companies) to review requests from researchers for access to clinical trial protocols, patient level clinical trial data and study level clinical trial data.

Information will then be shared with “qualified scientific and medical researchers upon request and subject to terms necessary to protect patient privacy and confidential commercial information.”

In addition, drug companies will make publicly …
The diagnosis and management of interstitial lung diseases
Authors: A. Wallis, K. Spinks
Journal: BMJ (2015)

#### The bottom line

The interstitial lung diseases comprise a complex group of pulmonary disorders principally affecting the pulmonary interstitium. The group includes idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, sarcoidosis, and connective tissue disease associated interstitial lung disease.

#### Sources and selection criteria

We carried out an electronic search of Medline and Embase for relevant original papers and systematic reviews using the search terms “pulmonary fibrosis”, “interstitial lung disease”, and “diffuse parenchymal lung disease”, prioritising those published from 2010. Relevant articles from the Cochrane databases and personal references were also included.

Recent years have witnessed an expansion of research studies, large randomised controlled trials, and novel treatments in interstitial lung diseases with the potential to change the treatment landscape for patients. For some patients the aim will be to control symptoms, whereas for others it may be possible to stabilise disease or even achieve remission. 

The aim of this review is to highlight the salient features in the history and examination that can suggest a specific interstitial lung disease, and …
PMO-175 Can a 3-month “stopping rule” for pegylated-interferon-α be applied to a UK population of chronic hepatitis B infected patients of mixed genotype?
Authors: U S Gill, L Payaniandy, J Schulz, V Ross, Y Kallis, P Kooner, R Marley, I Ushiro-Lumb, G R Foster, P T F Kennedy
Journal: Gut (2012)

<h3>Introduction</h3> Stopping rules have been proposed for the early discontinuation of Pegylated-Interferon-α (PEG-IFN-α) therapy in those patients who are considered unlikely to respond. Recent studies have shown that no reduction in quantitative HBsAg and the absence of &gt;2 log decline in HBV DNA at 12 weeks therapy can predict non-response. However, these data are almost exclusively from genotype A and D cohorts. Here we test how robust this strategy would be in clinical practice and whether this rule could be applied to a UK population of diverse HBV genotypes. <h3>Methods</h3> 49 patients (male=35) were treated with PEG-IFNα for CHB over the course of the study. Ten patients remain on therapy and eight patients discontinued due to poor compliance or intolerance. 31 patients (male=20), HBeAg positive (n=24), median age 31 (range 18–55) completed 48 weeks PEG-IFNα and were included in the analysis. HBV genotype was recorded for all patients (A=6, B=5, C=10, D=9, E=1). ALT, HBV DNA and HBsAg was quantified at baseline and longitudinally at 12-week intervals. <h3>Results</h3> Of the 31 patients, 10 were considered responders; seven were HBeAg positive and seroconverted on therapy and three were HBeAg negative pre-therapy and considered responders with sustained immune control off treatment. The decline in HBV DNA and qHBsAg by 12 weeks was 3.99 log, 0.17 log (HBeAg positive group) and 2.9 log, 0.5 log (HBeAg negative group) respectively. 16/31 patients were non-genotype A or D. Of the responders from this group there was a decline in HBV DNA and qHBsAg of 4.10 log and 0.58 log respectively by 12 weeks. On sub-group analysis by genotype, there was no statistically significant difference in HBV DNA and qHBsAg decline at 12 weeks across all genotypes, when comparing HBV DNA and qHBsAg between genotype A and D and non A and D patients (p=0.40 and 1.0 respectively). More over adopting the rule of &gt;2 log decline in HBV DNA and no decline in qHBsAg by 12 weeks, reveals we would not exclude those likely to respond; as all responders achieve the outlined viral response by 12 weeks therapy. <h3>Conclusion</h3> These data highlight the utility of this stopping rule for PEG-IFNα across all genotypes. The absence of &gt;2 log decline in HBV DNA and reduction in qHBsAg at 12 weeks therapy makes a favourable response unlikely. This rule should be adopted in clinical practice to avoid poorly tolerated side effects and the cost of completing 48 weeks therapy. Furthermore, this 12-week milestone would allow the early switch to an oral antiviral in PEG-IFNα non-responders. <h3>Competing interests</h3> None declared.
Mucosal colonisation with Lactobacillus casei mitigates barrier injury induced by exposure to trinitronbenzene sulphonic acid
Authors: M Llopis
Journal: Gut (2005)

<b>Background:</b> Trinitrobenzene sulphonic acid (TNBS) induces chronic transmural inflammatory lesions in the rat colon. Injury is facilitated by barrier disruption and invasion of commensal bacteria. However, certain bacteria have shown anti-inflammatory properties in in vitro models. <b>Aim:</b> To investigate in vivo the anti-inflammatory effect of <i>Lactobacillus casei</i> DN-114 001. <b>Methods:</b> Rats with a colonic segment excluded from faecal transit were surgically prepared. After washing the lumen with antibiotics, the excluded segment was recolonised (control group: standard flora of rat origin; test group: standard flora and <i>L casei</i>). Microbial colonisation was confirmed by culture of segment washing, and colitis was then induced by instillation of TNBS. One day after, intestinal lesions were blindly graded by macro- and microscopic scores, and myeloperoxidase activity measured in tissue homogenates. Translocation of bacteria to mesenteric lymph nodes, spleen and liver was investigated. <b>Results:</b> Test rats showed a smaller area of mucosal injury than control rats (p&lt;0.05). Maximum depth lesion scores were similar in both groups but myeloperoxidase activity was lower in test than in control rats (p&lt;0.05). Remarkably, bacterial translocation was quantitatively lower (p&lt;0.01) and less frequent (p&lt;0.05) in test than in control rats. <b>Conclusion:</b> In rats colonised with <i>L casei</i>, mucosal injury, inflammatory response, and barrier disruption after TNBS challenge were attenuated. Bacterial communities colonising the mucosa can modify inflammatory responses to luminal challenges.
Inheritance of antibody specificity V. Anti-2-phenyloxazolone in the mouse.
Authors: O Näkelä, M Kaartinen, J L Pelkonen, K Karjalainen
Journal: The Journal of Experimental Medicine (1978)

Antibodies to hapten 2-phenyloxazolone (phOx) of all BALB/c and DBA/2 mice have the same idiotype and the same major (public) isoelectric focusing pattern whose main spectrotype is called Ox-1. Neither of these characteristics could be readily demonstrated in anti-phOx antibodies of C57BL, C3H or LP mice; these antibodies were heterogeneous, and lacked public spectrotypes. Also, a fine specificty difference could be demonstrated between anti-phOx antibodies of BALB/c and C5MBL mice; the latter have a higher relative affinity than the former for a structural analogue of phOx (2-o-iodophenyloxazolone). The three BALB/c characteristics were inherited in congenic and recombinant inbred strains as an allotype-linked block, defining a new VH marker, VHphOx. Murine anti-phOx antibodies were found to exhibit three types of conservatism: (a) Every individual mouse of strains BALB/c, DBA/2 or BAB-14 had an almost indistinguishable IEF pattern. (b) These patterns (and the cross-reactive idiotype) remained virtually unchanged during an immunization course of 70 days. (c) An identical idiotype (and in some cases IEF pattern) was present in mouse strains of five different allogroups.
Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD)
Authors: Winston Dunn, Arun J. Sanyal, Elizabeth M. Brunt, Aynur Unalp-Arida, Michael Donohue, Arthur J. McCullough, Jeffrey B. Schwimmer
Journal: Journal of Hepatology (2012)
Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia
Authors: Christopher T Johansen, Jian Wang, Matthew B Lanktree, Henian Cao, Adam D McIntyre, Matthew R Ban, Rebecca A Martins, Brooke A Kennedy, Reina G Hassell, Maartje E Visser, Stephen M Schwartz, Benjamin F Voight, Roberto Elosua, Veikko Salomaa, Christopher J O'Donnell, Geesje M Dallinga-Thie, Sonia S Anand, Salim Yusuf, Murray W Huff, Sekar Kathiresan, Robert A Hegele
Journal: Nature Genetics (2010)
Enhanced expression of membrane type-1 matrix metalloproteinase in mesangial proliferative glomerulonephritis.
Authors: K Hayashi, S Osada, K Shofuda, S Horikoshi, I Shirato, Y Tomino
Journal: Journal of the American Society of Nephrology (1998)

Matrix metalloproteinase-2 (MMP-2, gelatinase A) is involved in the inflammatory and sclerotic events of glomerular diseases. Newly identified membrane-type matrix metalloproteinases (MT-MMP) have been shown to activate specifically proMMP-2. To date, several types of MT-MMP have been cloned; however, their expressions in glomerular diseases have not been evaluated. To investigate the role of MT-MMP in glomerular diseases, the glomerular gene expression and enzymatic activity of MT-MMP were examined during the time course of nephritis induced in rats by anti-Thy1.1 antibody injection. Both MT1-MMP and MMP-2 mRNA expression increased prominently 5 and 10 d after anti-Thy1.1 antibody injection and decreased thereafter, as assayed by semiquantitative reverse transcription-PCR. In contrast, there were no remarkable changes in the gene expression of MT2-MMP between normal and diseased tissue, and that of MT3-MMP was not detected in isolated glomeruli by reverse transcription-PCR analysis. The activation of proMMP-2 as analyzed by gelatin zymography correlated with the glomerular MT1-MMP gene expression, suggesting that proMMP-2 was activated by MT1-MMP. Protein and mRNA expression of fibronectin, one of the major mesangial matrix proteins and substrate of MMP-2, were also synchronized with MT1-MMP and MMP-2 expression. In situ hybridization revealed intense MT1-MMP mRNA expression in the proliferating mesangial cells. Interestingly, MT1-MMP gene expression exhibited a similar distribution as alpha-smooth muscle actin expression, which was closely associated with mesangial phenotypic change. These results suggest that among the newly identified MT-MMP, MT1-MMP may play the central role in activation of proMMP-2. Furthermore, the enhancement of MT1-MMP and MMP-2 expression associated with mesangial phenotypic change may contribute to the development of anti-Thy1.1 antibody-induced glomerulonephritis and remodeling of extracellular matrices.
General Trends in the Utilization of Structural Factors Contributing to Biological Complexity
Authors: Dong Yang, Fan Zhong, Dong Li, Zhongyang Liu, Handong Wei, Ying Jiang, Fuchu He
Journal: Molecular Biology and Evolution (2012)

During evolution, proteins containing newly emerged domains and the increasing proportion of multidomain proteins in the full genome-encoded proteome (GEP) have substantially contributed to increasing biological complexity. However, it is not known how these two potential structural factors are preferentially utilized at given physiological states. Here, we classified proteins according to domain number and domain age and explored the general trends across species for the utilization of proteins from GEP to various certain-state proteomes (CSPs, i.e., all the proteins expressed at certain physiological states). We found that multidomain proteins or only older domain-containing proteins are significantly overrepresented in CSPs compared with GEP, which is a trend that is stronger in multicellular organisms than in unicellular organisms. Interestingly, the strengths of overrepresentation decreased during evolution of multicellular eukaryotes. When comparing across CSPs, we found that multidomain proteins are more overrepresented in complex tissues than in simpler ones, whereas no difference among proteins with domains of different ages is evident between complex and simple tissues. Thus, biological complexity under certain conditions is more significantly realized by diverse domain organization than by the emergence of new types of domain. In addition, we found that multidomain or only older domain-containing proteins tend to evolve slowly and generally are under stronger purifying selection, which may partly result from their general overrepresentation trends in CSPs.
Blocking effect of lyt-2 antibodies on T cell functions.
Authors: N Hollander, E Pillemer, I L Weissman
Journal: The Journal of Experimental Medicine (1980)

Monoclonal anti-Lyt-2 antibodies blocked effector function of cytotoxic thymus-derived (T) cells in the absence of added complement. Cytolysis of both allogeneic cells and syngeneic lymphoma or sarcoma target cells was inhibited at the level of the effector lymphocytes. Anti-Lyt-1 and anti-Thy-1 antibodies did not block killer cells. Proliferation of T cells in mixed lymphocyte culture was also inhibited by anti-Lyt-2, but not affected by anti-Lyt-1 or anti-Thy-1 antibodies. Although Lyt-1+ lymphocytes were required in the mixed lymphocyte reaction as helper cells for proliferation of Lyt-2+ lymphocytes, their helper function was not affected by the presence of Lyt-1 antibodies. Thus, although anti-Lyt-1, anti-Lyt-2 and anti-Thy-1 were of the same gamma 2A immunoglobulin class, had high titers, and interacted with T cells to the same extent, only anti-Lyt-2 blocked T cell functions. Polyclonal activation of T lymphocytes by concanavalin A, in contrast to activation by alloantigens, was not inhibited by Lyt-2 antibodies, suggesting that Lyt-2 antibodies interfere with T cell function at the level of the T cell antigen-receptor. The role which Lyt-2 molecules may play in T cell function is discussed.
Age-related Reduction Of S100A8/A9 In Chronic Rhinosinusitis Is Associated With Increased Production Of Soluble gp130
Authors: S.H. Lee, K. Hulse, J. Siebert, J. Norton, D.B. Conley, R. Chandra, R.C. Kern, S. Hong, R.P. Schleimer, S.H. Cho
Journal: Journal of Allergy and Clinical Immunology (2012)
Methylation profiling identifies 2 groups of gliomas according to their tumorigenesis
Authors: J. Laffaire, S. Everhard, A. Idbaih, E. Criniere, Y. Marie, A. de Reynies, R. Schiappa, K. Mokhtari, K. Hoang-Xuan, M. Sanson, J.-Y. Delattre, J. Thillet, F. Ducray
Journal: Neuro-Oncology (2010)

Extensive genomic and gene expression studies have been performed in gliomas, but the epigenetic alterations that characterize different subtypes of gliomas remain largely unknown. Here, we analyzed the methylation patterns of 807 genes (1536 CpGs) in a series of 33 low-grade gliomas (LGGs), 36 glioblastomas (GBMs), 8 paired initial and recurrent gliomas, and 9 controls. This analysis was performed with Illumina's Golden Gate Bead methylation arrays and was correlated with clinical, histological, genomic, gene expression, and genotyping data, including IDH1 mutations. Unsupervised hierarchical clustering resulted in 2 groups of gliomas: a group corresponding to de novo GBMs and a group consisting of LGGs, recurrent anaplastic gliomas, and secondary GBMs. When compared with de novo GBMs and controls, this latter group was characterized by a very high frequency of IDH1 mutations and by a hypermethylated profile similar to the recently described glioma CpG island methylator phenotype. MGMT methylation was more frequent in this group. Among the LGG cluster, 1p19q codeleted LGG displayed a distinct methylation profile. A study of paired initial and recurrent gliomas demonstrated that methylation profiles were remarkably stable across glioma evolution, even during anaplastic transformation, suggesting that epigenetic alterations occur early during gliomagenesis. Using the Cancer Genome Atlas data set, we demonstrated that GBM samples that had an LGG-like hypermethylated profile had a high rate of IDH1 mutations and a better outcome. Finally, we identified several hypermethylated and downregulated genes that may be associated with LGG and GBM oncogenesis, LGG oncogenesis, 1p19q codeleted LGG oncogenesis, and GBM oncogenesis.
Le Pied en Pratique Rheumatologique: Pathologie Articularie
Authors: A. S. J. Dixon
Journal: Annals of the Rheumatic Diseases (1984)

Nuclear magnetic resonance (NMR) tomographic imaging for popliteal cysts in RA 59 sive, and accurate method of assessing objectively the presence of and changes in popliteal cysts and syno- vial inflammation in rheumatoid arthritis.It is expected that further development of the technique will lead to improvement in the resolution of NMR images and enhance the accuracy of the localisation of T, values.
Asthma and Airway Hyperresponsiveness in Children with Eosinophilic Esophagitis: EGF and FGF-2 As a Link
Authors: Nadia L. Krupp, Sarita Sehra, Sandeep K. Gupta, Mark H. Kaplan, Robert S. Tepper
Journal: Journal of Allergy and Clinical Immunology (2014)
Radiographic patterns of acute chest syndrome
Authors: Armand Mekontso Dessap
Journal: Thorax (2015)

on paediatric and adult clinical studies.While discussing our paper, 2 the reviewer seems to have misinterpreted our results when saying that consolidation is more severe in the apex of adult sickle cell disease patients with acute chest syndrome.In fact, CT and bedside chest radiography showed that lung parenchyma was increasingly consolidated from apex to base. 2 This distribution is in accordance with previous studies, 3 4 but may vary with age, with young children having more upper and middle lobe disease, contrarily to adult patients.
Acute effects of inspiratory pressure support during exercise in patients with COPD
Authors: A. van 't Hul, R. Gosselink, P. Hollander, P. Postmus, G. Kwakkel
Journal: European Respiratory Journal (2003)

The aim of the present study was to evaluate the acute effects of inspiratory pressure support (IPS) of 5 cmH 2 O (IPS 5 ) and 10 cmH 2 O (IPS 10 ) on exercise endurance. Forty-five patients with COPD (mean forced expiratory volume in one second (FEV 1 )=39±14% pred) performed three constant-load endurance tests on a cycle ergometer at 75% of maximal workload. One test was without IPS, one test with IPS 5 , and one with IPS 10 . No statistically significant difference was found in exercise endurance between tests without IPS and IPS 5 (4.2±2.6 versus 4.4±2.9 min). In contrast, IPS 10 resulted in a statistically significant increase in endurance compared with exercise without IPS (6.3±6.7 versus 4.2±2.6 min), as well as compared with exercise with IPS 5 (6.3±6.7 versus 4.4±2.9 min). A wide scatter in individual responses to IPS was found, ranging from a deterioration of 1.6 min (−36%) to an improvement of 16.3 min (+445%). In only 15 patients, the increase in endurance exceeded the upper limit of the 95% confidence interval. Stepwise multiple regression analysis showed that maximal inspiratory pressure was the most important determinant of the increase in exercise endurance due to the application of IPS 10 . It was concluded that in contrast to inspiratory pressure support of 5 cmH 2 O, the application of inspiratory pressure support of 10 cmH 2 O during exercise resulted in a statistically significant improvement in exercise endurance in patients with COPD compared with exercise without inspiratory pressure support. However, on an individual basis, large differences in responses were found. Inspiratory muscle weakness was revealed as a determinant of improvement in exercise endurance due to the application of inspiratory pressure support of 10 cmH 2 O, explaining only 24% of the variance in outcome.