tbuckley/cabot-search huggingface dataset:
The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model
Authors: S LIM, Y KIM, Y AHN, M JEONG, M HONG, S JOO, K NAM, J CHO, P KANG, J PARK
Journal: Cardiovascular Research (2006)

This study was designed to examine whether mesenchymal stem cells (MSCs) transduced with Akt enhance cardiac repair after transplantation into the ischemic porcine heart.MSCs isolated from porcine bone marrow and transduced with myr-Akt were transplanted into porcine hearts after experimental myocardial infarction (MI) using intracoronary injection [Group I, vehicle; Group II, MSCs; Group III, Akt-MSCs]. Myocardial single photon emission tomography (M-SPECT) was performed to assess myocardial function and the infarcted area. Pigs were also sacrificed for immunohistochemical characterization and histologic analysis. In addition, in vitro assays were performed to examine the resistance of Akt-MSCs to H(2)O(2) stimulation.Transplantation of MSCs into the ischemic porcine myocardium (Group II) increased the left ventricular ejection fraction (DeltaLV EF; -6.3 +/- 15.1% versus 0.5 +/- 6.4%, P < 0.001) and decreased the Deltaarea of MI (6.8+/-5.6% versus -5.0+/-5.3%, P < 0.001) compared with the vehicle control (Group I). Transplantation of MSCs transduced with myr-Akt (Group III) resulted in further improvement in DeltaLV EF (-6.3 +/- 15.1% versus 5.8 +/- 11.3%, P < 0.001) and in Deltaarea of MI (6.8 +/- 5.6% versus -17.0 +/- 7.6%, P < 0.001). Akt-MSCs were more resistant to apoptosis, and the levels of extracellular signal-regulated protein kinase (ERK) activation and vascular endothelial growth factor (VEGF) were higher in H(2)O(2)-stimulated Akt-MSCs.Cellular transplantation of Akt-MSCs further enhances the repair of injured myocardium compared to MSC transplantation alone by increasing the number of viable MSCs after cellular transplantation.
mDYRK3 kinase is expressed selectively in late erythroid progenitor cells and attenuates colony-forming unit–erythroid development
Authors: Justin N. Geiger, Geoffry T. Knudsen, Leigh Panek, Ajay K. Pandit, Michael D. Yoder, Kenneth A. Lord, Caretha L. Creasy, Brian M. Burns, Peter Gaines, Susan B. Dillon, Don M. Wojchowski
Journal: Blood (2001)
An Address on REST, WORK, AND PLAY IN HEALTH AND DISEASE
Authors: E. F. Buzzard
Journal: BMJ (1930)

Wiir., our President honiour-ed miie xvitlh an invitation to a(diress yout to-day, I did mxiv best to visualize the con- ditions under xvhicli I slhould lhave to carry ouit miy taski rliii came to the conclusion-that xx-ork and ldla, wxould be aI)ll)rolriate subjects for diseussion at this meeting, and thatt rlest oi this, the last day, xvoild iiot be withouit its se(luctive appe.,al to sonme of uls.Questions in egar d to inLldiligelce ill wAork, play, and i-est are so often put before uis ill or1 Plrofessional calacity, aiid are so ofteni answx-ered ithi inore respect to tra(lition than to exlperience, tliat tfley deserve the reconsideration duie to all possible factor.sn i l the lproduction or maintenianice of health anld disease.W'hiile it -is true that play andl rest -are geneally, and in deed not uni)nopularly, reCogn izedl as p)rophylactic an (1 remedial agenlt.s of no mean-value, the position of xvork is; miore precarious in the minds of the profession and of the lub)lic, and it may be that it has earned a reputation for etiological mischiief based oni somewhat slender evidlence.It is not surprising it is only in accor d xvith human niature-that wh-lien the cause of an illness is in doubt, over-inldulgence in xwork is a more acceptable velrdict than oxer -iii(lul'eiice in other tlii-s su cli as foo(, drinki, or tobacco.Buit a vei-dict xhich is most xelcome is not alwavs the best foun-ded, anid thei medical professioni, bearing in mind thie well-recognized goodl healtlh aiid longevity of its members, slhouild sutrely hesitate to agree that over-xvorkinig can be 1held resp)onsible for disea se or (leathl, witlhoult a careful examiiinationi of the testimiony stiu)))oi'tl)g that (loctrinie.It mllighlt at fir'st sight be presumed(l tlat ouir knoxvledge of the phy siology of the inervois system prlovides us wN-ith piliciplies sufficienitly reliable to giui(le u1s in prescribing *work, rest, or play; but, lhelpful as sueli knowledge is, it is nlot vet equal to solvinig all the lprob)lellos xwitl xliili -e nare conifronte(d, aiid xe mnimst still loolk to clliical experience for lig-,hIt a nid lea m-niniig.Onl tlIe otlhel-hanld, clillical experience is of little value
Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study
Authors: D. Stolz, N. Smyrnios, P. Eggimann, H. Pargger, N. Thakkar, M. Siegemund, S. Marsch, A. Azzola, J. Rakic, B. Mueller, M. Tamm
Journal: European Respiratory Journal (2009)

In patients with ventilator-associated pneumonia (VAP), guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy. In a multicentre, randomised, controlled trial, 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group) with an antibiotic regimen selected by the treating physician. The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis. Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset (13 (2–21) days versus 9.5 (1.5–17) days). This translated into a reduction in the overall duration of antibiotic therapy of 27% in the procalcitonin group (p = 0.038). After adjustment for age, microbiology and centre effect, the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines (hazard rate 1.6, 95% CI 1.02–2.71). The number of mechanical ventilation-free days alive, intensive care unit-free days alive, length of hospital stay and mortality rate on day 28 for the two groups were similar. Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia.
Developmental Origin, Growth, and Three-Dimensional Architecture of the Atrioventricular Conduction Axis of the Mouse Heart
Authors: Wim T.J. Aanhaanen, Mathilda T.M. Mommersteeg, Julia Norden, Vincent Wakker, Corrie de Gier-de Vries, Robert H. Anderson, Andreas Kispert, Antoon F.M. Moorman, Vincent M. Christoffels
Journal: Circulation Research (2010)

The clinically important atrioventricular conduction axis is structurally complex and heterogeneous, and its molecular composition and developmental origin are uncertain.To assess the molecular composition and 3D architecture of the atrioventricular conduction axis in the postnatal mouse heart and to define the developmental origin of its component parts.We generated an interactive 3D model of the atrioventricular junctions in the mouse heart using the patterns of expression of Tbx3, Hcn4, Cx40, Cx43, Cx45, and Nav1.5, which are important for conduction system function. We found extensive figure-of-eight rings of nodal and transitional cells around the mitral and tricuspid junctions and in the base of the atrial septum. The rings included the compact node and nodal extensions. We then used genetic lineage labeling tools (Tbx2(+/Cre), Mef2c-AHF-Cre, Tbx18(+/Cre)), along with morphometric analyses, to assess the developmental origin of the specific components of the axis. The majority of the atrial components, including the atrioventricular rings and compact node, are derived from the embryonic atrioventricular canal. The atrioventricular bundle, including the lower cells of the atrioventricular node, in contrast, is derived from the ventricular myocardium. No contributions to the conduction system myocardium were identified from the sinus venosus, the epicardium, or the dorsal mesenchymal protrusion.The atrioventricular conduction axis comprises multiple domains with distinctive molecular signatures. The atrial part proliferates from the embryonic atrioventricular canal, along with myocytes derived from the developing atrial septum. The atrioventricular bundle and lower nodal cells are derived from ventricular myocardium.
Prior Publication Productivity, Grant Percentile Ranking, and Topic-Normalized Citation Impact of NHLBI Cardiovascular R01 Grants
Authors: Jonathan R. Kaltman, Frank J. Evans, Narasimhan S. Danthi, Colin O. Wu, Donna M. DiMichele, Michael S. Lauer
Journal: Circulation Research (2014)

We previously demonstrated absence of association between peer-review-derived percentile ranking and raw citation impact in a large cohort of National Heart, Lung, and Blood Institute cardiovascular R01 grants, but we did not consider pregrant investigator publication productivity. We also did not normalize citation counts for scientific field, type of article, and year of publication.To determine whether measures of investigator prior productivity predict a grant's subsequent scientific impact as measured by normalized citation metrics.We identified 1492 investigator-initiated de novo National Heart, Lung, and Blood Institute R01 grant applications funded between 2001 and 2008 and linked the publications from these grants to their InCites (Thompson Reuters) citation record. InCites provides a normalized citation count for each publication stratifying by year of publication, type of publication, and field of science. The coprimary end points for this analysis were the normalized citation impact per million dollars allocated and the number of publications per grant that has normalized citation rate in the top decile per million dollars allocated (top 10% articles). Prior productivity measures included the number of National Heart, Lung, and Blood Institute-supported publications each principal investigator published in the 5 years before grant review and the corresponding prior normalized citation impact score. After accounting for potential confounders, there was no association between peer-review percentile ranking and bibliometric end points (all adjusted P>0.5). However, prior productivity was predictive (P<0.0001).Even after normalizing citation counts, we confirmed a lack of association between peer-review grant percentile ranking and grant citation impact. However, prior investigator publication productivity was predictive of grant-specific citation impact.
Residency Training at a Crossroads: Duty-Hour Standards 2010
Authors: Kevin G. Volpp, William Friedman, Patrick S. Romano, Amy Rosen, Jeffrey H. Silber
Journal: Annals of Internal Medicine (2010)

In 2003, the Accreditation Council for Graduate Medical Education (ACGME) implemented a single duty-hour standard nationwide. The evidence to date suggests that this neither improved nor worsened patient outcomes. In June 2010, the ACGME proposed a new set of duty-hour standards for implementation in July 2011. The main disadvantage of this approach is that there is no ability to determine whether different standards would have worked better to reduce resident fatigue while improving patient safety. Many unanswered questions remain about how to design duty-hour standards, but relatively little evidence exists. In addition, the same approach may not work in all specialties and all hospitals. A more flexible, dynamic policy that emphasizes ongoing testing and evaluation would be more likely to achieve improvements in clinical and educational outcomes.
Bortezomib Sensitizes Primary Human Astrocytoma Cells of WHO Grades I to IV for Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis
Authors: Ronald Koschny, Heidrun Holland, Jaromir Sykora, Tobias L. Haas, Martin R. Sprick, Tom M. Ganten, Wolfgang Krupp, Manfred Bauer, Peter Ahnert, Jürgen Meixensberger, Henning Walczak
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Malignant gliomas are the most aggressive human brain tumors without any curative treatment. The antitumor effect of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in gliomas has thus far only been thoroughly established in tumor cell lines. In the present study, we investigated the therapeutic potential of TRAIL in primary human glioma cells. Experimental Design: We isolated primary tumor cells from 13 astrocytoma and oligoastrocytoma patients of all four WHO grades of malignancy and compared the levels of TRAIL-induced apoptosis induction, long-term tumor cell survival, caspase, and caspase target cleavage. Results: We established a stable culture model for isolated primary human glioma cells. In contrast to cell lines, isolated primary tumor cells from all investigated glioma patients were highly TRAIL resistant. Regardless of the tumor heterogeneity, cotreatment with the proteasome inhibitor bortezomib efficiently sensitized all primary glioma samples for TRAIL-induced apoptosis and tremendously reduced their clonogenic survival. Due to the pleiotropic effect of bortezomibenhanced TRAIL DISC formation upon TRAIL triggering, down-regulation of cFLIPL and activation of the intrinsic apoptosis pathway seem to cooperatively contribute to the antitumor effect of bortezomib/TRAIL cotreatment. Conclusion: TRAIL sensitivity of tumor cell lines is not a reliable predictor for the behavior of primary tumor cells. The widespread TRAIL resistance in primary glioma cells described here questions the therapeutic clinical benefit of TRAIL as a monotherapeutic agent. Overcoming TRAIL resistance by bortezomib cotreatment might, however, provide a powerful therapeutic option for glioma patients.
Genetic association study of<i>CYP1A1</i>polymorphisms identifies risk haplotypes in nonsmall cell lung cancer
Authors: C. M. Wright, J. E. Larsen, M. L. Colosimo, J. J. Barr, L. Chen, R. E. McLachlan, I. A. Yang, R. V. Bowman, K. M. Fong
Journal: European Respiratory Journal (2009)

Lung cancer remains a leading cause of disease globally, with smoking being the largest single cause. Phase I enzymes, including cytochrome P 450 , family 1, subfamily A, polypeptide 1 (CYP1A1), are involved in the activation of carcinogens, such as polycyclic aromatic hydrocarbons, to reactive intermediates that are capable of binding covalently to DNA to form DNA adducts, potentially initiating the carcinogenic process. The aim of the present study was to investigate the association of CYP1A1 gene polymorphisms and haplotypes with lung cancer risk. A case–control study was carried out on 1,040 nonsmall cell lung cancer (NSCLC) cases and 784 controls to investigate three CYP1A1 variants, CYP1A1*2A (rs4646903; thymidine to cytosine substitution at nucleotide 3801 (3801T&gt;C)), CYP1A1*2C (rs1048943; 2455A&gt;G; substitution of isoleucine 462 with valine (exon 7)) and CYP1A1*4 (rs1799814; 2453C&gt;A; substitution of threonine 461 with asparagine (exon 7)) using PCR restriction fragment length polymorphism methods. The CYP1A1*2A and CYP1A1*2C variants were significantly over-represented in NSCLC cases compared with controls, whereas the CYP1A1*4 variant was under-represented. CYP1A1 haplotypes (in allele order CYP1A1*4, CYP1A1*2C, CYP1A1 * 2A ) CGC and CGT were associated with an increased risk of lung cancer, whereas AAT was associated with decreased lung cancer risk in this population. The present study has identified risk haplotypes for CYP1A1 in NSCLC and confirmed that CYP1A1 polymorphisms are a minor risk factor for NSCLC.
Cyclin G2 Dysregulation in Human Oral Cancer
Authors: Yong Kim, Satoru Shintani, Yohko Kohno, Rong Zhang, David T. Wong
Journal: Cancer Research (2004)

Using expression microarray, we have previously shown that human cyclin G2 (hCG2) is significantly down-regulated in laser capture microdissected oral cancer epithelia. Western analysis showed detectable hCG2 protein in normal (2 of 2) but not in malignant (4 of 4) oral keratinocyte cell lines. Immunohistochemistry analysis done on oral cancers showed that normal oral mucosa (100%, 12 of 12) and 69.1% (47 of 68) of dysplastic oral epithelia expressed readily detectable hCG2 in the nuclei. However, only 11.1% of oral cancer epithelia (14 of 126) showed mild hCG2 nuclear staining. Interestingly, of the oral cancers devoid of nuclear hCG2 (112 cases), 58 cases (52%) showed cytoplasmic hCG2 immunostaining, whereas the other 54 cases (48%) exhibited neither nuclear nor cytoplasmic hCG2 staining. In vitro functional study by ectopic restoration of hCG2 expression in the human malignant squamous cell carcinoma (SCC) line SCC15 resulted in a significant inhibition of cellular proliferation (P < 0.001) and colony formation (P < 2 x 10(-5)) with increased population of G(1) phase and decreased in S phase (P < 0.01). Furthermore, stable down-regulation of hCG2 by short interference RNA-based gene silencing in immortalized normal oral keratinocytes resulted in enhanced cell growth with increase in S and prominently in G(2) phase. Because hCG2 has been implicated as a negative regulator in cell cycle progression, our results support that hCG2 dysregulation may play an important role in epithelial transformation and the early stages of human oral cancer development.
Regulation of Thick Ascending Limb Ion Transporter Abundance in Response to Altered Acid/Base Intake
Authors: GHEUN-HO KIM, CAROLYN ECELBARGER, MARK A. KNEPPER, RANDALL K. PACKER
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Changes in ammonium excretion with acid/base perturbations are dependent on changes in medullary ammonium accumulation mediated by active NH 4 + absorption by the medullary thick ascending limb. To investigate whether alterations in the abundance of medullary thick ascending limb ion transporters, namely the apical Na + /K + (NH 4 + )/2Cl - -cotransporter (BSC-1), the apical Na + /H + -exchanger (NHE3), and the Na + /K + -ATPase α1-subunit, may be responsible in part for altered medullary ammonium accumulation, semiquantitative immunoblotting studies were performed using homogenates from the inner stripe of the rat renal outer medulla. After 7 d of NH 4 Cl (7.2 mmol/220 g body wt per d) loading (associated with increased medullary ammonium accumulation), neither BSC-1 nor Na + /K + -ATPase protein expression was altered, but NHE3 protein abundance was significantly increased. On the other hand, both BSC-1 and Na + /K + -ATPase protein abundance was increased significantly in rats fed NaHCO 3 (7.2 mmol/220 g body wt per d) for 7 d. Rats fed a high-NaCl diet (7.7 mEq Na + /220 g body wt per d) for 5 d also showed marked increases in both BSC-1 and Na + /K + -ATPase expression. The expression level of NHE3 protein did not change with either NaHCO 3 or high NaCl intake. None of these three transporters showed a significant difference in abundance between the groups fed equimolar (7.2 mmol/220 g body wt per d for 7 d) NaHCO 3 or NaCl. It is concluded that outer medullary BSC-1 and Na + /K + -ATPase α1-subunit protein abundance is increased by chronic Na + loading but not by acid/base perturbations and that outer medullary NHE3 protein abundance is increased by chronic NH 4 Cl loading.
STUDIES ON EXPERIMENTAL PNEUMONIA
Authors: Russell L. Cecil, Francis G. Blake
Journal: The Journal of Experimental Medicine (1920)

1. Experimental Pneumococcus Type I pneumonia in monkeys confers on them an immunity which protects them against subsequent infection with the homologous type of pneumococcus. The duration of this immunity has not been determined. 2. A certain amount of cross-immunity against the other fixed types of pneumococcus pneumonia may or may not be present following experimental Pneumococcus Type I pneumonia. The degree of cross-immunity is difficult to measure and probably varies widely with the individual monkey. 3. Experimental Pneumococcus Type IV pneumonia in monkeys confers slight if any protection against subsequent infection with the same, or with an homologous strain of Pneumococcus Type IV. 4. There is no evidence in monkeys of cross-immunity against Pneumococcus Type IV pneumonia following Pneumococcus Type I pneumonia; and conversely, Pneumococcus Type IV pneumonia confers no cross-immunity against Pneumococcus Type I pneumonia.
<i>TRAF1–C5</i>as a Risk Locus for Rheumatoid Arthritis — A Genomewide Study
Authors: Robert M Plenge, Mark Seielstad, Leonid Padyukov, Annette T Lee, Elaine F Remmers, Bo Ding, Anthony Liew, Houman Khalili, Alamelu Chandrasekaran, Leela R L Davies, Wentian Li, Adrian K S Tan, Carine Bonnard, Rick T H Ong, Anbupalam Thalamuthu, Sven Pettersson, Chunyu Liu, Chao Tian, Wei V Chen, John P Carulli, Evan M Beckman, David Altshuler, Lars Alfredsson, Lindsey A Criswell, Christopher I Amos, Michael F Seldin, Daniel L Kastner, Lars Klareskog, Peter K Gregersen
Journal: New England Journal of Medicine (2007)

Rheumatoid arthritis has a complex mode of inheritance. Although HLA-DRB1 and PTPN22 are well-established susceptibility loci, other genes that confer a modest level of risk have been identified recently. We carried out a genomewide association analysis to identify additional genetic loci associated with an increased risk of rheumatoid arthritis.
P138 Moderate-intensity Activity is Associated with Reduced Cardiovascular Risk Factors in COPD
Authors: AM Albarrati, NS Gale, S Enright, IC Munnery, MM Munnery, JR Cockcroft, DJ Shale
Journal: Thorax (2013)

<h3>Background</h3> Steps measurement is a common measure of daily physical activity, but cannot define the intensity of physical activity. Moderate intensity activity is recommended type to maintain a basic level of health (1), but in patients with COPD, the effect of moderate intensity activity on systemic manifestations has not been studied. We hypothesised that patients with higher moderate activity time would have lower frailty, inflammation and cardiovascular risk. <h3>Methods</h3> As part of a longitudinal study in COPD (ARCADE), daily physical activity was recorded over seven days using a multisensor armband (SenseWear Pro armband) in 75 stable patients with COPD. Spirometry, body composition, aortic stiffness, comprehensive geriatric assessment, C-reactive protein (CRP) and fibrinogen were also determined. Moderate-intensity activity was determined by the monitor for activity between 3 to 6 METs. <h3>Results</h3> Patients (42 males) mean (SD) age was 66 (7) years, BMI 27.5 (5.2) Kg/m<sup>2</sup>, FEV<sub>1</sub> predicted 55 (17)% and moderate activity time 1.46 (1.23) hours. The time spent on moderate activities was not related to age or FEV<sub>1</sub>pred. The moderate activity time related to BMI (r = -0.41), fat mass (r = -0.38) and fat percentage (r = -0.37), all p &lt; 0.001, but not with fat free mass. However, none of these parameters related to the number of steps. Moderate activity time was inversely associated with aortic stiffness, r = -0.31, p &lt; 0.01, CRP, fibrinogen (r = -0.26; r = -0.24, respectively) and frailty score all p &lt; 0.05. However, the number of steps only related to the inflammatory markers. <h3>Conclusion</h3> The changes in frailty and cardiovascular risk factors including adipose tissue, aortic stiffness and inflammatory markers are linked to the proportion of time in moderate activities as their predominant form of activity. <h3>References</h3> Elsawy, B and Higgins, K. (2010) <i>Am Fam Physician</i> 1;81(1):55–59.