tbuckley/cabot-search huggingface dataset:
New function for high density lipoproteins. Their participation in intravascular reactions of bacterial lipopolysaccharides.
Authors: R J Ulevitch, A R Johnston, D B Weinstein
Journal: Journal of Clinical Investigation (1979)

The addition of bacterial lipopolysaccharide (LPS) from Escherichia coli 0111:B4 or Salmonella minnesota R595 to plasma (or serum) resulted in a marked reduction of the hydrated buoyant density of the parent LPS (0111:B4 [d = 1.44 g/cm3] and R595 [d = 1.38 g/cm3]), to d less than 1.2 g/cm3. This reduction in buoyant density to less than 1.2 g/cm3 of the LPS required plasma (or serum) lipid. Delipidation of plasma (or serum) by extraction with n-butanol/diisopropyl ether (40/60, vol:vol) prevented the conversion of the parent LPS to a form with d less than 1.2 g/cm3. Reversal of the effect of delipidation was accomplished by the addition of physiologic concentrations of high density lipoprotein (HDL). In contrast, as much as two times normal serum concentration of low density or very low density lipoprotein were ineffective. The ability of normal plasma (or serum) to inhibit the pyrogenic activity of LPS, lost after delipidation, was also restored after the addition of HDL. Preliminary results suggested that prior modifications of the LPS, probably disaggregation, may be required before interaction with HDL.
Secretor status and Helicobacter pylori infection are independent risk factors for gastroduodenal disease.
Authors: W Dickey, J S Collins, R G Watson, J M Sloan, K G Porter
Journal: Gut (1993)

The hypothesis that non-secretors of ABO blood group antigens, a group shown to be more susceptible to certain bacterial infections, may be at greater risk of gastroduodenal disease because of increased susceptibility to Helicobacter pylori infection was investigated. Of 101 patients with symptoms of dyspepsia who were undergoing endoscopy, 32% were non-secretors (determined from Lewis blood group phenotype), 36% had endoscopically visible gastroduodenal disease (antral gastritis, gastric ulcer, erosive duodenitis, duodenal ulcer or some combination), and 58% had H pylori detected in antral biopsy specimens. Non-secretors and patients with H pylori infection were significantly more likely to have gastroduodenal disease (p = 0.02 and p = 0.002 respectively). There was, however, no significant association between secretor status and H pylori infection, logistic regression analysis confirming that these were independently associated with gastroduodenal disease. Overall, the relative risk of gastroduodenal disease for non-secretors compared with secretors was 1.9 (95% confidence intervals 1.2, 3.2). Non-secretion of ABO blood group antigens is not related to H pylori infection but is independently and significantly associated with endoscopic gastroduodenal disease. The mechanism of this remains to be explained.
Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Aaron E Miller, Jerry S Wolinsky, Ludwig Kappos, Giancarlo Comi, Mark S Freedman, Tomas P Olsson, Deborah Bauer, Myriam Benamor, Philippe Truffinet, Paul W O'Connor
Journal: The Lancet Neurology (2014)
The metallopeptidase neprilysin is a hypoxia-induced prognostic factor in lung adenocarcinoma
Authors: Katharina Leithner, Christoph Wohlkoenig, Elvira Stacher, Jörg Lindenmann, Nicole A. Hofmann, Birgit Ebner, Franz Quehenberger, Freyja-Maria Smolle-Jüttner, Sjaak Philipsen, Helmut H. Popper, Andelko Hrzenjak, Andrea Olschewski, Horst Olschewski
Journal: European Respiratory Journal (2012)

Identification of hypoxia-induced pathways might lead to novel therapeutic targets in solid cancers. A comparative expression profiling study was performed in hypoxic and normoxic  ex vivo  cultured lung cancer fragments with preserved tumor stroma and 3D-structure. A considerable overlap was found between hypoxia-regulated genes from the  ex vivo  lung cancer model and published hypoxia-signatures. The stem cell marker neprilysin (membrane metallo-endopeptidase, MME, CD10), which was consistently up-regulated by hypoxia in the histological subtypes in our study, has not been reported so far to be hypoxia-induced in cancer. Neprilysin has been shown to be expressed by stroma cells, e.g. cancer-associated fibroblasts. Immunohistochemistry for neprilysin in fresh NSCLC specimens and normoxic or hypoxic fragments revealed a localization in both, stroma cells and neoplastic tumor cells. To assess a possible role of neprilysin in lung cancer progression we analyzed the association of neprilysin expression and overall survival in NSCLC patients from public microarray datasets. High expression of neprilysin was significantly associated with poor overall survival in 182 adenocarcinoma patients in a multivariate meta-analysis ( P =0.000012) and in adenocarcinoma patients from two individual datasets. As a conclusion, neprilysin is a hypoxia-induced, independent adverse prognostic factor in surgically treated lung adenocarcinoma patients. The results of this study suggest an important role of stroma-derived hypoxia-induced factors for lung cancer progression.
Warm-blooded isochore structure in Nile crocodile and turtle
Authors: S. Hughes, D. Zelus, D. Mouchiroud
Journal: Molecular Biology and Evolution (1999)

The genomes of warm-blooded vertebrates are characterized by a strong heterogeneity in base composition, with GC-rich and GC-poor isochores. The GC content of sequences, especially in third codon positions, is highly correlated with that of the isochore they are embedded in. In amphibian and fish genomes, GC-rich isochores are nearly absent. Thus, it has been proposed that the GC increase in a part of mammalian and avian genomes represents an adaptation to homeothermy. To test this selective hypothesis, we sequenced marker protein genes in two cold-blooded vertebrates, the Nile crocodile Crocodylus niloticus (10 genes) and the red-eared slider Trachemys scripta elegans (6 genes). The analysis of base composition in third codon position of this original data set shows that the Nile crocodile and the turtle also exhibit GC-rich isochores, which rules out the homeothermy hypothesis. Instead, we propose that the GC increase results from a mutational bias that took place earlier than the adaptation to homeothermy in birds and before the turtle/crocodile divergence. Surprisingly, the isochore structure appears very similar between the red-eared slider and the Nile crocodile than between the chicken and the Nile crocodile. This point questions the phylogenetic position of turtles as a basal lineage of extant reptiles. We also observed a regular molecular clock in the Archosauria, which enables us, by using a more extended data set, to confirm Kumar and Hedges's dating of the bird-crocodile split.
The clinician's guide to pancreaticobiliary disorders
Authors: M. M Lerch
Journal: Gut (2007)

Edited by Gregory G Ginsberg and Nuzhat A Ahmad. New Jersey: Published by Slack Incorporated, 2006, pp 400. ISBN 1-55642-694-1

Ginsberg and Ahmad from Philadelphia have edited a compendium on pancreaticobiliary disorders within the Clinician’s Guide series. Overall, this is a concise book and makes for good reading. The referencing is somewhat inconsistent from chapter to chapter. Sometimes citations are extensive, and sometimes chapters are rather short on direct references to statements made in the text. Some chapters like chapter 1 recommend further reading instead, whereas others such as chapters 11 and 2 are well referenced.

At the start of the book, congenital abnormalities of the pancreas, such as pancreas divisum, are outlined, and guidelines for interventional therapy are given. Chapter 2 on gallstones and gallbladder disorders is detailed on the pathobiology of gallstone formation. Some facts are repeated in Chapter 3 on choledocholithiasis, which also contains the technical intricacies of various types of sphincterotomes. Unfortunately, no reference is provided for the indicated 25% late complication rate after endoscopic sphincterotomy, a proportion I regard as very high. In Chapter 5, …
Characterization of a kininogenase from rat vascular tissue resembling tissue kallikrein.
Authors: H Nolly, A G Scicli, G Scicli, O A Carretero
Journal: Circulation Research (1985)

A kininogenase resembling glandular kallikrein was partially purified from vascular tissue and characterized. Saline-perfused rat tail arteries and veins were homogenized in 0.25 M sucrose containing 10 mM Tris-HCl (pH 7.4). The homogenate was centrifuged at 105,000 g for 60 minutes, and a vascular kininogenase was purified from the supernatant by chromatofocusing, affinity chromatography on immobilized antibodies against rat urinary kallikrein, and gel filtration on Sephadex G-100. The inhibitory effects of antibodies against rat urinary kallikrein were tested with equivalent kinin-forming concentrations of rat urinary kallikrein and vascular kininogenase. Kininogenase activities of both enzymes were similarly inhibited by both polyclonal and monoclonal antibodies. Aprotinin (1,000 KIU) completely inhibited vascular kininogenase activity, while soybean trypsin inhibitor (100 micrograms) did not modify its kinin-forming activity. Vascular kininogenase and rat urinary kallikrein had the same elution volume when chromatographed on a Sephadex G-100 column, and had similar mobilities in 10% polyacrylamide gel electrophoresis. Kinins released by vascular kininogenase were identified as bradykinin by reverse-phase high performance liquid chromatography. Rat vascular kininogenase appears to be similar to glandular kallikrein. Kinins released locally by vascular kininogenase may contribute to the regulation of vascular tone.
The mutational spectrum of type 1 von Willebrand disease: results from a Canadian cohort study
Authors: Paula D. James, Colleen Notley, Carol Hegadorn, Jayne Leggo, Angie Tuttle, Shawn Tinlin, Christine Brown, Chandler Andrews, Andrea Labelle, Yvette Chirinian, Lee O'Brien, Maha Othman, Georges Rivard, Dilys Rapson, Christine Hough, David Lillicrap
Journal: Blood (2006)
Variability of hospital resources for acute care of COPD patients: the European COPD Audit
Authors: Jose Luis López-Campos, Sylvia Hartl, Francisco Pozo-Rodriguez, C. Michael Roberts
Journal: European Respiratory Journal (2013)

Studies have suggested that larger hospitals have better resources and provide better care than smaller ones. This study aimed to explore the relationship between hospital size, resources, organisation of care and adherence to guidelines. The European COPD Audit was designed as a pilot study of clinical care and a survey of resources and organisation of care. Data were entered by clinicians to a multilingual web tool and analysed centrally. Participating hospitals were divided into tertiles on the basis of bed numbers and comparisons made of the resources, organisation of care and adherence to guidelines across the three size groups. 13 national societies provided data on 425 hospitals. The mean number of beds per tertile was 220 (lower), 479 (middle), and 989 (upper). Large hospitals were more likely to have resources and increased numbers of staff; hospital performance measures were related in a minority of indicators only. Adherence to guidelines also varied with hospital size, but the differences were small and inconsistent. There is a wide variation in the size, resources and organisation of care across Europe for hospitals providing chronic obstructive pulmonary disease care. While larger hospitals have more resources, this does not always equate to better accessibility or quality of care for patients.
Environmental exposure in relation to exhaled nitric oxide in newborns: is it all about timing?
Authors: P. Latzin, U. Frey
Journal: European Respiratory Journal (2008)

Exhaled nitric oxide (eNO) is a marker of eosinophilic airway inflammation. It is increasingly used for the diagnosis and monitoring of asthmatic lung disease in adults as well as children 1, 2 and is believed to be helpful in titrating steroids or in predicting relapse in established asthma 3, 4. Although it is known that eNO is increased in healthy atopics 5, its role during the development of asthmatic airway disease is not understood. Only a few studies have examined whether eNO is already elevated before the occurrence of respiratory symptoms or in children that are prone to developing asthma 6, 7. Data published so far showed an interaction with smoke exposure, suggesting that, at least in high-risk children, eNO may play a role in the very initial phases of recurrent respiratory symptoms 6. It is tempting to speculate that eNO is a pre-existing marker before allergic inflammation of the airways occurs and that children can be “eNO phenotyped” early in life 8, enabling the identification of those with a high risk for later asthma development. However, before this can be done it is necessary to understand the natural course of eNO during the time period of fastest lung development, and the influence of external environmental stimuli on this course with possible long-term consequences 9.

In this issue of the European Respiratory Journal , Gabriele et al. 10 help to understand the issues of smoke exposure, airway symptoms and eNO in healthy infants 10. Gabriele et al. 10 examined the effect of pre- and post-natal smoke exposure and respiratory tract infections on eNO measured at age 4–17 weeks in an unselected birth cohort. They found that compared with unexposed infants, post-natal smoke exposure alone led to an increase in eNO, whereas …
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) promotes glioma cell invasion through induction of NF-κB-inducing kinase (NIK) and noncanonical NF-κB signaling
Authors: Evan M Cherry, Dong W Lee, Ji-Ung Jung, Raquel Sitcheran
Journal: Molecular Cancer (2015)

High-grade gliomas are one of the most invasive and therapy-resistant cancers. We have recently shown that noncanonical NF-κB/RelB signaling is a potent driver of tumorigenesis and invasion in the aggressive, mesenchymal subtype of glioma. However, the relevant signals that induce activation of noncanonical NF-κB signaling in glioma and its function relative to the canonical NF-κB pathway remain elusive. The ability of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) to regulate NF-κB signaling and promote tumor progression was investigated in both established and primary high-grade glioma tumor lines using a three-dimensional (3-D) collagen invasion assay. The roles of specific NF-κB proteins in regulating glioma cell invasion and expression of Matrix Metalloproteinase 9 (MMP9) in response to TWEAK were evaluated using shRNA-mediated loss-of-function studies. The ability of NF-κB-inducing kinase (NIK) to promote glioma growth in vivo was investigated using an orthotopic xenograft mouse model. In glioma cells that display elevated noncanonical NF-κB signaling, loss of RelB attenuates invasion without affecting RelA expression or phosphorylation and RelB is sufficient to promote invasion in the absence of RelA. The cytokine TWEAK preferentially activates the noncanonical NF-κB pathway through induction of p100 processing to p52 and nuclear accumulation of both RelB and p52 without activating the canonical NF-κB pathway. Moreover, TWEAK, but not TNFα, significantly increases NIK mRNA levels. TWEAK also promotes noncanonical NFκB-dependent MMP9 expression and glioma cell invasion. Finally, expression of NIK is sufficient to increase gliomagenesis in vivo. Our data establish a key role for NIK and noncanonical NF-κB in mediating TWEAK-induced, MMP-dependent glioma cell invasion. The findings also demonstrate that TWEAK induces noncanonical NF-κB signaling and signal-specific regulation of NIK mRNA expression. Together, these studies reveal the important role of noncanonical NF-κB signaling in regulating glioma invasiveness and highlight the therapeutic potential of targeting activation of NIK in this deadly disease.
A large subpopulation of avian T cells express a homologue of the mammalian T gamma/delta receptor.
Authors: J T Sowder, C L Chen, L L Ager, M M Chan, M D Cooper
Journal: The Journal of Experimental Medicine (1988)

This report describes an avian TCR molecule, TCR1, whose molecular characteristics, signal-transducing property, and tissue distribution suggest that it is a homologue of the mammalian TCR-gamma/delta. TCR1+ cells are the first to be generated in the thymus during ontogeny, preceding other T3+ cells by approximately 3 d. Unlike their mammalian counterpart, TCR1+ cells constitute a relatively large subpopulation of peripheral T cells in mature chickens. These results suggest a phylogenetically important role for this receptor in T cell development and function.
Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial
Authors: Helena von Hertzen, Gilda Piaggio, Alexandre Peregoudov, Juhong Ding, Junling Chen, Si Song, György Bártfai, Ernest Ng, Kristina Gemzell-Danielsson, Amindavaa Oyunbileg, Shangchun Wu, Weiyu Cheng, Frank Lüdicke, Alenka Pretnar-Darovec, Rosemary Kirkman, Suneeta Mittal, Archil Khomassuridze, Dan Apter
Journal: The Lancet (2002)
Are kinetic chain rowing exercises relevant in shoulder and trunk injury prevention training?
Authors: K De Mey, L Danneels, B Cagnie, A Cools
Journal: British Journal of Sports Medicine (2011)

Background Recent guidelines emphasise the importance of functional kinetic chain exercises during injury prevention training. Knowledge of muscle activation levels during various unilateral rowing exercises is lacking. Objective To describe and compare the activation levels of scapulothoracic and lumbopelvic muscle parts during eight variations of the high rowing exercise. Design Descriptive study. Exercise performance was standardised and individualised based on height, age and body weight. Setting Controlled laboratory study at Ghent University (Belgium). Participants 30 young healthy volunteers with a history of being active in sports and able to perform the exercises correctly. Interventions Activation levels of the upper trapezius (UT) and lower trapezius (LT) muscles of the dominant shoulder, and multifidus (MF) and erector spinae (ES) muscles at both sides of the trunk were investigated. Exercises were performed in front of a pulley apparatus. Main outcome measurements Individual muscle activation levels captured by surface Electromyography. Results Shoulder muscle activation was characterised by superior LT (&gt;12.5% MVIC) over UT (&lt;7.12% MVIC) muscle activation across exercises. Rowing in a static unipedal squat position revealed highest LT muscle activation (18.33% MVIC). Upright exercises (squatted or lunged) showed generally higher trunk muscle activation levels compared to a sitting or standing execution. Superior MF (&gt;21% MVIC) over ES (&lt;30.13% MVIC) muscle activation was found during all upright exercises, except during static bipedal squatting. Highest MF muscle activation was found heterolateral to arm movement during the dynamic single leg squat version of the exercise (33.26% MVIC; p&lt;0.05). Conclusion High rowing exercises recruit posterior shoulder and trunk muscles relevant in injury prevention training. Unilateral rowing during a single leg squat position or movement seems most favourable for athletic injury prevention training purposes.
Improvement of Alveolar Glutathione and Lung Function but Not Oxidative State in Cystic Fibrosis
Authors: Matthias Griese, Jan Ramakers, Angela Krasselt, Vitaliy Starosta, Silke van Koningsbruggen, Rainald Fischer, Felix Ratjen, Bernhard Müllinger, Rudolf M. Huber, Konrad Maier, Ernst Rietschel, Gerhard Scheuch
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Chronic neutrophilic inflammation leads to oxidative damage, which may play an important role in the pathogenesis of cystic fibrosis lung disease. Bronchoalveolar lavage levels of the antioxidant glutathione are diminished in patients with cystic fibrosis. Here we evaluated the effects of glutathione aerosol on lower airway glutathione levels, lung function, and oxidative status. Pulmonary deposition of a radiolabeled monodisperse aerosol generated with a Pari LC Star nebulizer (Allergy Asthma Technology, Morton Grove, IL) connected to an AKITA inhalation device (Inamed, Gauting, Germany) was determined in six patients. In 17 additional patients bronchoalveolar lavage fluid was assessed before and after 14 days of inhalation with thrice-daily doses of 300 or 450 mg of glutathione. Intrathoracic deposition was 86.3 +/- 1.4% of the emitted dose. Glutathione concentration in lavage 1 hour postinhalation was increased three- to fourfold and was still almost doubled 12 hours postinhalation. FEV(1) transiently dropped after inhalation but increased compared with pretreatment values after 14 days (p < 0.001). This improvement was not related to the lavage content of oxidized proteins and lipids, which did not change with treatment. These results show that, using a new inhalation device with high efficacy, glutathione treatment of the lower airways is feasible. Reversion of markers of oxidative injury may need longer treatment, higher doses, or different types of antioxidants.
Insulin in obstetrics: a main parameter in the management of pregnancy
Authors: M Ciampelli
Journal: Human Reproduction Update (1998)

Insulin plays a central role in human pregnancy. Maternal insulin sensitivity decreases with advancing gestation in order to provide glucose and possibly other nutrients for feto-placental growth and energy needs. Moreover, alterations of insulin metabolism are clearly involved in the development of gestational diabetes. In recent years, hyperinsulinaemia has been also proposed as a possible pathogenic factor in the development of gestational hypertension and preeclampsia; furthermore it has also been postulated that there is an involvement of insulin sensitivity in fetal growth restriction. These intriguing data hae stimulated our interest in summarizing the physiopathological mechanisms by which the pancreatic hormone could be involved in obstetrics.
Nasal Nitric Oxide (NNO) in Patients with Allergic Rhinitis and Healthy Volunteers Following Pollen Exposure in an Environmental Challenge Chamber (ECC)
Authors: J.M. Hohlfeld, M. Larbig, I. Paczkowski, H. Hecker, N. Krug
Journal: Journal of Allergy and Clinical Immunology (2006)

RATIONALE: The aim of this study was to investigate the effect of a standardized allergen exposure in an ECC on nNO in atopic (A) and healthy (H) individuals. METHODS: Patients with seasonal allergic rhinitis (n=60) and age-matched non-allergic controls (n=60) were exposed to grass pollen in an ECC for 4 hours at two visits separated by 2 weeks. Nasal NO, nasal symptoms (TNSS), and rhinomanometry were measured and assessed at baseline, at 4 hours and the next day. RESULTS: At baseline, nNO was similar between groups (A: 938 ppb, H: 920 ppb). Nasal NO was significantly decreased in atopics at 4 hours (848 ppb) when their TNSS was maximal and nasal flow was minimal. In contrast, nNO significantly increased in healthy subjects at 4 hours (984 ppb) while their TNSS and nasal flow did not change. At 24 hours, when TNSS and nasal flow were normal again, nNO increased significantly both in allergic (1097 ppb) and healthy (1035 ppb) subjects with a significant difference between groups (p=0.032). In both groups, the course of nNO was highly reproducible between sessions and revealed no carry-over effects. CONCLUSIONS: Although nNO can be measured with high reproducibility between ECC sessions, our data question its allergen specificity and suggest its influence from nasal obstruction.