tbuckley/cabot-search huggingface dataset:
Targeting Neuropilin 1 as an Antitumor Strategy in Lung Cancer
Authors: Tse-Ming Hong, Yuh-Ling Chen, Yi-Ying Wu, Ang Yuan, Yu-Chih Chao, Yi-Chuan Chung, Ming-Heng Wu, Shuenn-Chen Yang, Szu-Hua Pan, Jin-Yuan Shih, Wing-Kai Chan, Pan-Chyr Yang
Journal: Clinical Cancer Research (2007)

Neuropilin 1 (NRP1) is a mediator of lung branching and angiogenesis in embryonic development and angiogenesis in cancer. The role of NRP1 in cancer progression is not fully elucidated. We investigated the role of NRP1 in cancer invasion and tumor angiogenesis, its signaling pathways, prognostic significance, and therapeutic implications.Sixty patients with non-small cell lung cancer (NSCLC) were studied. NRP1 mRNA expression was measured using real-time quantitative reverse-transcription PCR. NRP1 and cancer cell invasion, angiogenesis, and signaling pathways were studied using NRP1 stimulation by vascular endothelial growth factor 165 (VEGF(165)) and NRP1 inhibition by small interfering RNAs (siRNA), soluble NRP1 (sNRP1), and NRP1-inhibition peptides. The NRP1-inhibition peptides were identified using a phage display peptide library.NSCLC patients with high expression of NRP1 had shorter disease-free (P = 0.0162) and overall survival (P = 0.0164; log-rank test). Multivariate analyses showed NRP1 is an independent prognostic factor in overall (HR, 2.37, 95% CI = 1.15 to 4.9, P = 0.0196) and disease-free survival [hazard ratio (HR), 2.38; 95% confidence interval (95% CI), 1.15-4.91; P = 0.0195] of NSCLC patients. Knockdown of NRP1 suppressed cancer cell migration, invasion, filopodia formation, tumorigenesis, angiogenesis, and in vivo metastasis. NRP1 signaling pathways involved VEGF receptor 2 and phosphoinositide-3-kinase (PI3K) and Akt activation. Two potent synthetic anti-NRP1 peptides, DG1 and DG2, which block NRP1 signaling pathways and suppress tumorigenesis, cancer invasion, and angiogenesis, were identified.NRP1 is a cancer invasion and angiogenesis enhancer. NRP1 expression is an independent predictor of cancer relapse and poor survival in NSCLC patients. NRP1 plays a critical role in tumorigenesis, cancer invasion, and angiogenesis through VEGF, PI3K, and Akt pathways. NRP1 may have potential as a new therapeutic target in NSCLC.
Association of domestic exposure to volatile organic compounds with asthma in young children
Authors: K Rumchev
Journal: Thorax (2004)

To investigate the association between domestic exposure to volatile organic compounds (VOCs) and asthma in young children.A population based case-control study was conducted in Perth, Western Australia in children aged between 6 months and 3 years. Cases (n = 88) were children recruited at Princess Margaret Hospital accident and emergency department and discharged with asthma as the primary diagnosis; 104 controls consisted of children from the same age group without an asthma diagnosis identified through the Health Department of Western Australia. Information regarding the health status of the study children and characteristics of the home was collected using a standardised questionnaire. Exposure to VOCs, average temperature and relative humidity were measured in winter and summer in the living room of each participating household.Cases were exposed to significantly higher VOC levels (microg/m3) than controls (p<0.01). Most of the individual VOCs appeared to be significant risk factors for asthma with the highest odds ratios for benzene followed by ethylbenzene and toluene. For every 10 unit increase in the concentration of toluene and benzene (microg/m3) the risk of having asthma increased by almost two and three times, respectively.Domestic exposure to VOCs at levels below currently accepted recommendations may increase the risk of childhood asthma. Measurement of total VOCs may underestimate the risks associated with individual compounds.
Foot-in-Wallet Disease: Tripped Up by “Cost-Saving” Reductions?
Authors: Grant H. Skrepnek, Joseph L. Mills, David G. Armstrong
Journal: Diabetes Care (2014)

In the U.S., podiatric medical services are considered to be optional under Medicaid statutes, with an underlying assumption that these services are elective and can be performed by other providers. It may have been easily anticipated, therefore, that podiatric services were often included in line-item cuts in a number of state budgets under the recent period of economic austerity. Given this, the current research report used Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP) inpatient discharge records spanning 2006–2011 to assess changes in inpatient hospitalizations associated with diabetic foot ulcers (DFUs) among adult beneficiaries of Arizona Medicaid (Arizona Health Care Cost Containment System [AHCCCS]) following the October 2009 announcement of coverage cancellation to podiatric physicians intended to reduce costs (i.e., $351,000 saved from the $8.7 billion general fund, SB1003 and HB2003 within the …
Respiratory muscle function and exercise capacity in multiple sclerosis
Authors: K Foglio, E Clini, D Facchetti, M Vitacca, S Marangoni, M Bonomelli, N Ambrosino
Journal: European Respiratory Journal (1994)

Patients with multiple sclerosis (MS) show a poor exercise tolerance. A reduction in respiratory muscle strength has also been reported. The purpose of this study was to evaluate whether reduction in exercise tolerance was related to respiratory muscle dysfunction. Twenty four multiple sclerosis patients (mean +/- SD age: 48 +/- 9 yrs, duration of illness 12.2 +/- 6 yrs, severity of illness as assessed by Expanded Disability Scale Score (EDSS) 5.3 +/- 2), underwent detailed evaluation of lung function tests, arterial blood gas analysis, respiratory muscle strength and endurance, and exercise test on an arm ergometer. Sixteen of the 24 patients were able to perform the exercise test (Group I), whilst the other eight were not (group II). Arterial blood gases and lung function tests were normal for both groups. Respiratory muscle strength as assessed both by maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) was significantly reduced (MIP 18-76 cmH2O; MEP 16-82 cmH2O) compared to predicted values. Inspiratory muscle endurance time was significantly reduced in Group II in comparison to Group I (247 +/- 148 vs 397 +/- 154 s, respectively). Both MIP and MEP were significantly related to inspiratory muscle endurance time. Endurance time, MIP and MEP were inversely significantly related to duration of illness, whilst only endurance time was significantly related to Expanded Disability Scale Score.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of SNAT2 by Metabolic Acidosis Enhances Proteolysis in Skeletal Muscle
Authors: Kate Evans, Zeerak Nasim, Jeremy Brown, Emma Clapp, Amin Amin, Bin Yang, Terence P. Herbert, Alan Bevington
Journal: Journal of the American Society of Nephrology (2008)

Insulin resistance is a major cause of muscle wasting in patients with ESRD. Uremic metabolic acidosis impairs insulin signaling, which normally suppresses proteolysis. The low pH may inhibit the SNAT2 l-Glutamine (L-Gln) transporter, which controls protein synthesis via amino acid-dependent insulin signaling through mammalian target of rapamycin (mTOR). Whether SNAT2 also regulates signaling to pathways that control proteolysis is unknown. In this study, inhibition of SNAT2 with the selective competitive substrate methylaminoisobutyrate or metabolic acidosis (pH 7.1) depleted intracellular L-Gln and stimulated proteolysis in cultured L6 myotubes. At pH 7.1, inhibition of the proteasome led to greater depletion of L-Gln, indicating that amino acids liberated by proteolysis sustain L-Gln levels when SNAT2 is inhibited by acidosis. Acidosis shifted the dose-response curve for suppression of proteolysis by insulin to the right, confirming that acid increases proteolysis by inducing insulin resistance. Blocking mTOR or phosphatidylinositol-3-kinase (PI3K) increased proteolysis, indicating that both signaling pathways are involved in its regulation. When both mTOR and PI3K were inhibited, methylaminoisobutyrate or acidosis did not stimulate proteolysis further. Moreover, partial silencing of SNAT2 expression in myotubes and myoblasts with small interfering RNA stimulated proteolysis and impaired insulin signaling through PI3K. In conclusion, SNAT2 not only regulates mTOR but also regulates proteolysis through PI3K and provides a link among acidosis, insulin resistance, and protein wasting in skeletal muscle cells.
Extending the network perspective on comorbidity
Authors: Brian D. Haig, Frances M. Vertue
Journal: Behavioral and Brain Sciences (2010)

Abstract Cramer et al. make a good case for reconceptualizing comorbid psychopathologies in terms of complex network theory. We suggest the need for an extension of their network model to include reference to latent causes. We also draw attention to a neglected approach to theory appraisal that might usefully be incorporated into the methodology of network theory.
A certified plasmid reference material for the standardisation of BCR–ABL1 mRNA quantification by real-time quantitative PCR
Authors: H White, L Deprez, P Corbisier, V Hall, F Lin, S Mazoua, S Trapmann, A Aggerholm, H Andrikovics, S Akiki, G Barbany, N Boeckx, A Bench, M Catherwood, J-M Cayuela, S Chudleigh, T Clench, D Colomer, F Daraio, S Dulucq, J Farrugia, L Fletcher, L Foroni, R Ganderton, G Gerrard, E Gineikienė, S Hayette, H El Housni, B Izzo, M Jansson, P Johnels, T Jurcek, V Kairisto, A Kizilors, D-W Kim, T Lange, T Lion, K M Polakova, G Martinelli, S McCarron, P A Merle, B Milner, G Mitterbauer-Hohendanner, M Nagar, G Nickless, J Nomdedéu, D A Nymoen, E O Leibundgut, U Ozbek, T Pajič, H Pfeifer, C Preudhomme, K Raudsepp, G Romeo, T Sacha, R Talmaci, T Touloumenidou, V H J Van der Velden, P Waits, L Wang, E Wilkinson, G Wilson, D Wren, R Zadro, J Ziermann, K Zoi, M C Müller, A Hochhaus, H Schimmel, N C P Cross, H Emons
Journal: Leukemia (2014)

Serial quantification of BCR–ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR–ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 106, 1.08±0.11 × 105, 1.03±0.10 × 104, 1.02±0.09 × 103, 1.04±0.10 × 102 and 10.0±1.5 copies/μl. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR–ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR–ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors ( https://ec.europa.eu/jrc/en/reference-materials/catalogue/ ; CRM code ERM-AD623a-f).
Clonal populations of T cells in normal elderly humans: the T cell equivalent to "benign monoclonal gammapathy".
Authors: D N Posnett, R Sinha, S Kabak, C Russo
Journal: The Journal of Experimental Medicine (1994)

To determine whether T cells, like B cells, can become clonally expanded in normal individuals as a function of age, we compared the T cell V beta repertoire of cord blood to that of peripheral blood from normal donors over 65 yr of age. T cells from elderly subjects contained expanded subsets (greater than the mean+three standard deviations) of T cell receptor (TCR) V beta populations. These expanded subsets were observed primarily among CD8, but not CD4 cells, represented up to 37.5% of all CD8 cells, and were present in most elderly subjects. An expanded V beta 5.2/3 CD8 subset and a V beta 6.7a CD8 subset from separate donors were analyzed by reverse transcriptase-polymerase chain reaction, cloning and sequencing of the TCR beta chain VDJ junction. In both cases the expanded subsets were mono- or oligoclonal while control CD4 populations were polyclonal. Using two-color flow cytometry it was possible to identify the expanded V beta 6.7a subset as CD8+ CD28-CD11b+ cells. In three of five random old subjects similar expansions of V beta subsets were found specifically in the CD8+ CD28- subpopulation, an interesting subset of cytotoxic T lymphocytes, known to lack proliferative responses to TCR stimuli. It is common practice to use the demonstration of clonality as a diagnostic indicator for T cell lymphoma/leukemia. In view of the high frequency of expanded T clones of T cells in normal elderly subjects the diagnostic usefulness of this test should be reexamined.
HS-142-1, a potent antagonist of natriuretic peptides in vitro and in vivo.
Authors: P L Zhang, W Jiménez, H S Mackenzie, J Guo, J L Troy, J Ros, P Angeli, V Arroyo, B M Brenner
Journal: Journal of the American Society of Nephrology (1994)

To determine whether HS-142-1 (HS), a potent atrial natriuretic peptide (ANP) receptor antagonist, also inhibits the effects of brain natriuretic peptide (BNP), urodilatin (URO), and C-type natriuretic peptide, in vitro studies were carried out, demonstrating that HS inhibited production of cGMP by rat fetal lung fibroblast cells induced by ANP, BNP, URO, and C-type natriuretic peptide. Acute clearance studies were conducted in euvolemic Munich-Wistar rats under inactin anesthesia to characterize the effects of HS in vivo. In response to ANP, BNP, or URO (4 micrograms/kg priming dose plus 0.5 micrograms/kg per minute for 20 min), urine flow, absolute sodium excretion rates, and fractional sodium excretion exhibited similar increases (four- to fivefold) in vehicle-treated rats; these responses were, however, completely abolished by prior HS treatment. The tendency for GFR to rise during the infusion of natriuretic peptides (NP) was also blocked after HS. By contrast, HS did not block the renal effects of L-arginine, a precursor of nitric oxide, or of furosemide. Furthermore, the inhibition of endogenous NP by HS was associated with small but significant reductions in GFR and absolute and fractional sodium excretion in normal rats under euvolemic but not hydropenic conditions. These studies provide evidence that the observed effects of HS in vivo and in vitro are mediated exclusively by receptors of NP. Together, these data support the view that HS is a highly specific ligand for NP receptors, capable of antagonizing the renal effects not only of exogenous ANP, but also those of BNP and URO.
COMPLEMENT-DEPENDENT B-CELL ACTIVATION BY COBRA VENOM FACTOR AND OTHER MITOGENS?
Authors: Peter Dukor, Gebhard Schumann, Roland H. Gisler, Manfred Dierich, Wolfgang König, Ulrich Hadding, Dieter Bitter-Suermann
Journal: The Journal of Experimental Medicine (1974)

It has been proposed that two distinct signals are required for the triggering of the precursors of antibody-forming bone marrow-derived cells (B cells): (a) the binding of antigen or of a mitogen to the corresponding receptor sites on B-cell membranes and (b) the interaction of activated C3 with the C3 receptor of B lymphocytes. There is growing evidence that B-cell mitogens and T (thymus-derived cell)-independent antigens are capable of activating the alternate pathway of the complement system (bypass). Therefore, the effect of another potent bypass inducer was investigated with regard to B-cell activation and the role of C3. Purified, pyrogen-free cobra venom factor was mitogenic for both T and B lymphocytes (cortisone-resistant mouse thymus cells and lymph node lymphocytes from congenitally athymic mice). Venom factor could substitute for T cells by restoring the potential of antibody formation to sheep red blood cells in mouse B-cell cultures supplemented with macrophages or 2-mercaptoethanol. Venom factor may be capable of conferring activated C3 to the C3 receptor of B lymphocytes: preincubation of lymphoid cells with homologous serum or plasma, 10 mM EDTA, and sepharose-coupled venom factor converted with serum to an enzyme active against C3, inhibited their capacity to subsequently form rosettes with sheep erythrocytes sensitized with amboceptor and C5-deficient mouse complement. In the absence of EDTA, preincubation of freshly prepared B-cell suspensions with C3-sufficient homologous serum also blocked their subsequent interaction with complement-sensitized erythrocytes and at the same time rendered them reactive to an otherwise T-cell-specific mitogen. Moreover, mitogen induced B-cell proliferation in lymph node (but not in spleen) cell cultures, appeared to depend on the availability of exogenous C3: zymosan-absorbed fetal bovine serum (only 8.3% site-forming units remaining) supported T-cell activation by phytohemagglutinin, concanavalin A, and venom factor, but failed to sustain B-cell stimulation by pokeweed mitogen, lipopolysaccharide, and venom factor. T-cell-dependent antibody formation in composite cultures containing T cells or T-cell-substituting B-cell mitogens, B cells, and macrophages, always required the presence of C3-sufficient serum.
Cardiac Sarcoplasmic Reticulum Calcium Release and Load Are Enhanced by Subcellular cAMP Elevations in PI3Kγ-Deficient Mice
Authors: Benoit-Gilles Kerfant, Dominica Gidrewicz, Hui Sun, Gavin Y. Oudit, Josef M. Penninger, Peter H. Backx
Journal: Circulation Research (2005)

We recently showed that phosphoinositide-3-kinase-γ–deficient (PI3Kγ −/− ) mice have increased cardiac contractility without changes in heart size compared with control mice (ie, PI3Kγ +/+ or PI3Kγ +/− ). In this study, we show that PI3Kγ −/− cardiomyocytes have elevated Ca 2+ transient amplitudes with abbreviated decay kinetics compared with control under field-stimulation and voltage-clamp conditions. When Ca 2+ transients were eliminated with high Ca 2+ buffering, L-type Ca 2+ currents ( I Ca,L ), K + currents, and action potential duration (APD) were not different between the groups, whereas, in the presence of Ca 2+ transients, Ca 2+ -dependent phase of I Ca,L inactivation was abbreviated and APD at 90% repolarization was prolonged in PI3Kγ −/− mice. Excitation-contraction coupling (ECC) gain, sarcoplasmic reticulum (SR) Ca 2+ load, and SR Ca 2+ release fluxes measured as Ca 2+ spikes, were also increased in PI3Kγ −/− cardiomyocytes without detectable changes in Ca 2+ spikes kinetics. The cAMP inhibitor Rp-cAMP eliminated enhanced ECC and SR Ca 2+ load in PI3Kγ −/− without effects in control myocytes. On the other hand, the β-adrenergic receptor agonist isoproterenol increased I Ca,L and Ca 2+ transient equally by ≈2-fold in both PI3Kγ −/− and PI3Kγ +/− cardiomyocytes. Our results establish that PI3Kγ reduces cardiac contractility in a highly compartmentalized manner by inhibiting cAMP-mediated SR Ca 2+ loading without directly affecting other major modulators of ECC, such as AP and I Ca,L .
Protein-Leaking Membranes for Hemodialysis
Authors: Richard A. Ward
Journal: Journal of the American Society of Nephrology (2005)

A new class of membranes that leak protein has been developed for hemodialysis. These membranes provide greater clearances of low molecular weight proteins and small protein-bound solutes than do conventional high-flux dialysis membranes but at the cost of some albumin loss into the dialysate. Protein-leaking membranes have been used in a small number of clinical trials. The results of these trials suggest that protein-leaking membranes improve anemia correction, decrease plasma total homocysteine concentrations, and reduce plasma concentrations of glycosylated and oxidized proteins. However, it is not clear yet that routine use of protein-leaking membranes is warranted. Specific uremic toxins that are removed by protein-leaking membranes but not conventional high-flux membranes have not been identified. It is also unclear whether protein-leaking membranes offer benefits beyond those obtained with conventional high-flux membranes used in convective therapies, such as hemofiltration and hemodiafiltration. Finally, the amount of albumin loss that can be tolerated by hemodialysis patients in a long-term therapy has yet to be determined. Protein-leaking membranes offer a new approach to improving outcomes in hemodialysis, but whether their benefits will outweigh their disadvantages will require more basic and clinical research.
The cardiac atrial appendage stem cell: a new and promising candidate for myocardial repair
Authors: Remco Koninckx, Annick Daniëls, Severina Windmolders, Urbain Mees, Regina Macianskiene, Kanigula Mubagwa, Paul Steels, Luc Jamaer, Jasperina Dubois, Boris Robic, Marc Hendrikx, Jean-Luc Rummens, Karen Hensen
Journal: Cardiovascular Research (2012)

AimsConsiderable shortcomings in the treatment of myocardial infarction (MI) still exist and therefore mortality remains high. Cardiac stem cell (CSC) therapy is a promising approach for myocardial repair. However, identification and isolation of candidate CSCs is mainly based on the presence or absence of certain cell surface markers, which suffers from some drawbacks. In order to find a more specific and reliable identification and isolation method, we investigated whether CSCs can be isolated based on the high expression of aldehyde dehydrogenase (ALDH).
THE EFFECT OF TOPICALLY APPLIED BEOLAMETHASONE DIPROPIONATE ON ADRENAL FUNCTION
Authors: E. J. RAFFLE, W. Frain-Bell
Journal: British Journal of Dermatology (1967)

Journal Article THE EFFECT OF TOPICALLY APPLIED BEOLAMETHASONE DIPROPIONATE ON ADRENAL FUNCTION Get access E. J. RAFFLE, M.B., Ch.B., M.R.C.P., Edin., D.C.H., E. J. RAFFLE, M.B., Ch.B., M.R.C.P., Edin., D.C.H. Department of Dermatology, Royal Infirmary, Dundee Search for other works by this author on: Oxford Academic Google Scholar W. Frain‐Bell, M.D., F.R.C.P., Edin. W. Frain‐Bell, M.D., F.R.C.P., Edin. Department of Dermatology, Royal Infirmary, Dundee Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 79, Issue 8-9, 1 August 1967, Pages 487–490, https://doi.org/10.1111/j.1365-2133.1967.tb11536.x Published: 01 August 1967