tbuckley/cabot-search huggingface dataset:
Pair-tested renal reserve filtration capacity in kidney recipients and their donors.
Authors: P M ter Wee, A M Tegzess, A J Donker
Journal: Journal of the American Society of Nephrology (1994)

Subjects after kidney donation manifest an adaptive rise in GFR. In uninephrectomized rats, progressive glomerulosclerosis, which is induced by the compensatory glomerular hyperfiltration, develops. It has been assumed that testing the existence of renal reserve filtration capacity (RRFC) might be used to demonstrate such glomerular hyperfiltration in humans. In a paired way, the RRFC of 15 kidney recipients and their donors were investigated long term (4.9 +/- 0.8 (SE) yr) after surgery. Continuous infusions of (125I)iothalamate and (131I)hippuran were used to measure GFR and effective RPF (ERPF). RRFC was tested by the infusion of dopamine, amino acids, and a combined infusion of these agents. The GFR, ERPF, and RRFC of the recipients did not differ from that of their donors. RRFC had also been tested in 12 donors, before and short term (1.3 +/- 0.3 (SE) months) after the kidney donation. Thus, the RRFC of the kidney donors could be monitored longitudinally. GFR measured short term after kidney donation amounted to 62% (+/- 2.1% SE) of the value before donation and to 68% (+/- 1.7% SE; P < 0.005) of the value long term after donation. Short- and long-term ERPF both amounted to 68% of the value before donation. The RRFC tested with the amino acids of the donors before kidney donation did not differ from that either short-term or long term after donation. Likewise, the RRFC tested with the amino acids of the recipients was similar to that of the donors before kidney donation. In contrast, in kidney recipients and donors, both short and long term after donation, RRFC tested with dopamine was approximately halved compared with that of the donors before donation. It was concluded, first, that testing RRFC cannot be used to test the existence of maladaptive glomerular hyperfiltration in subjects with a single kidney: Second, GFR increases for years after kidney donation, probably because of the compensatory hypertrophy of the remaining kidney.
Chromium Treatment Has No Effect in Patients With Type 2 Diabetes in a Western Population
Authors: Nanne Kleefstra, Sebastiaan T. Houweling, Stephan J.L. Bakker, Simon Verhoeven, Rijk O.B. Gans, Betty Meyboom-de Jong, Henk J.G. Bilo
Journal: Diabetes Care (2007)

Chromium treatment has been reported to improve glycemic control in patients with type 2 diabetes. However, concern exists about the possible toxic effects of chromium picolinate. The aim of this study was to determine the effect of chromium treatment in the form of chromium yeast on glycemic control in a Western population of patients with type 2 diabetes who were being treated with oral hypoglycemic agents.In this 6-month, double-blind study, patients with moderate glycemic control, being treated with oral hypoglycemic agents, were randomly assigned to receive either a placebo or treatment with 400 microg of chromium daily in the form of chromium yeast. The primary efficacy parameter was a change in A1C. Secondary end points were changes in lipid profile, BMI, blood pressure, body fat, and insulin resistance.No differences were found for the change in A1C between the intervention and placebo groups, nor were any differences found between the groups for the secondary end points.There is no evidence that chromium in the form of chromium yeast is effective in improving glycemic control in Western patients with type 2 diabetes who are taking oral hypoglycemic agents.
Induction of B-Chronic Lymphocytic Leukemia Cell Apoptosis by Arsenic Trioxide Involves Suppression of the Phosphoinositide 3-Kinase/Akt Survival Pathway via <i>c-jun</i>-NH2 Terminal Kinase Activation and PTEN Upregulation
Authors: Javier Redondo-Muñoz, Elizabeth Escobar-Díaz, Mercedes Hernández del Cerro, Atanasio Pandiella, María José Terol, José A. García-Marco, Angeles García-Pardo
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Arsenic trioxide (ATO) induces B-cell chronic lymphocytic leukemia (B-CLL) cell apoptosis in vitro. We sought to study the mechanism involved in this effect and whether ATO is suitable for combination therapies with protein kinase inhibitors. Experimental Design: B-CLL cells were isolated from the peripheral blood of 28 patients. Cell viability studies with ATO alone or in combination with kinase inhibitors were done by flow cytometry, Western blotting, and immunofluorescence analyses. Results: After 48 hours, 3 μmol/L ATO induced apoptosis (average 75%) in all B-CLL samples studied and with minimal effect on normal peripheral blood lymphocytes. Apoptosis entailed Akt and NF-κB inactivation, XIAP downregulation, and PTEN upregulation, thus implying inhibition of the phosphoinositide 3-kinase (PI3K) survival pathway. Indeed, the combination of ATO and PI3K inhibitors increased the apoptotic effect of either agent alone. ATO also induced c-jun-NH2 terminal kinase (JNK) activation, and this was crucial and required for subsequent apoptotic events, as inhibiting JNK activity by either gene silencing or specific inhibitors prevented Akt and NF-κB inactivation, caspase activation, and mitochondrial damage. Moreover, JNK activation was the earliest response to ATO, preceding and determining reactive oxygen species production. Conclusions: We identified the mechanism involved in ATO action on B-CLL cells and show that the combination of low doses of ATO and PI3K inhibitors efficiently induces B-CLL cell death. ATO may therefore constitute an efficient treatment for B-CLL, particularly in combined therapies. Clin Cancer Res; 16(17); 4382–91. ©2010 AACR.
Role of Brainstem Sodium/Proton Exchanger 3 for Breathing Control during Chronic Acid–Base Imbalance
Authors: Heidrun Kiwull-Schöne, Peter Kiwull, Stilla Frede, Martin Wiemann
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

The sodium/proton exchanger (NHE) 3 is expressed in brainstem areas with prevalence for central chemosensitivity. Selective NHE3 inhibitors can evoke CO(2) mimetic responses both in vitro and in vivo, demonstrating the functional significance of this pH-regulating protein. Moreover, levels of NHE3 expression are inversely correlated to interindividual differences of baseline ventilation in conscious rabbits.We explored the influence of chronic acid-base disturbances on mRNA levels of brainstem NHE3 in relation to breathing control.Alveolar ventilation (Va), blood gases, systemic base excess (BE), and metabolic Vco(2) were determined in rabbits shortly after exposure to either CO(2)-enriched air for 3 days (n = 5) or to ammonium chloride with drinking water for 2 days (n = 6). Untreated animals served as controls (n = 24). NHE3 mRNA within the obex region was quantified by real-time reverse transcription-polymerase chain reaction.After chronic hypercapnia, we found a compensatory rise of BE (mean +/- SEM) to 5.3 +/- 0.5 mmol x L(-1) with slightly elevated Pa(CO(2)). Brainstem NHE3 mRNA as well as Va were not significantly different from control levels. In the NH(4)Cl group, arterial pH was approximately 0.09 units lower than control, and BE decreased to -6.5 +/- 1.6 mmol x L(-1) with slightly decreased Pa(CO(2)), but considerably reduced Va (by approximately 25%; P < 0.05) and Vco(2). Concomitantly, brainstem NHE3 mRNA had increased from control level of 1.45 +/- 0.19 to 3.64 +/- 0.37 fg cDNA/mug RNA; P < 0.01.Expression of brainstem NHE3 is up-regulated by chronic metabolic acidosis but not by prolonged hypercapnia. It is proposed that elevated brainstem NHE3 expression contributes to limit maladaptive hyperventilation during metabolic acidosis.
Prevalence of a Healthy Lifestyle Among Individuals With Cardiovascular Disease in High-, Middle- and Low-Income Countries
Authors: Koon Teo, Scott Lear, Shofiqul Islam, Prem Mony, Mahshid Dehghan, Wei Li, Annika Rosengren, Patricio Lopez-Jaramillo, Rafael Diaz, Gustavo Oliveira, Maizatullifah Miskan, Sumathy Rangarajan, Romaina Iqbal, Rafal Ilow, Thandi Puone, Ahmad Bahonar, Sadi Gulec, Ebtihal A. Darwish, Fernando Lanas, Krishnapillai Vijaykumar, Omar Rahman, Jephat Chifamba, Yan Hou, Ning Li, Salim Yusuf, on behalf of the PURE Investigators
Journal: JAMA (2013)

2][3] Smoking cessation is associ-ated with a lower risk of death and myocardial infarction, high-quality diets 1,4 and regular exercise are associated with lower risk of death or recurrent cardiovascular disease events after a myocardial infarction. 1-3Thus, avoidance of smoking or its cessation, improving diet quality, and increasing physical ac-tivity level are recommended for secondary prevention of cardiovascular disease.
Effect of CPAP on blood pressure in patients with minimally symptomatic obstructive sleep apnoea: a meta-analysis using individual patient data from four randomised controlled trials
Authors: Daniel J Bratton, John R Stradling, Ferran Barbé, Malcolm Kohler
Journal: Thorax (2014)

<h3>Background</h3> CPAP reduces blood pressure (BP) in patients with symptomatic obstructive sleep apnoea (OSA). Whether the same benefit is present in patients with minimally symptomatic OSA is unclear, thus a meta-analysis of existing trial data is required. <h3>Methods</h3> The electronic databases Medline, Embase and trial registries were searched. Trials were eligible if they included patients with minimally symptomatic OSA, had randomised them to receive CPAP or either sham-CPAP or no CPAP, and recorded BP at baseline and follow-up. Individual participant data were obtained. Primary outcomes were absolute change in systolic and diastolic BP. <h3>Findings</h3> Five eligible trials were found (1219 patients) from which data from four studies (1206 patients) were obtained. Mean (SD) baseline systolic and diastolic BP across all four studies was 131.2 (15.8) mm Hg and 80.9 (10.4) mm Hg, respectively. There was a slight increase in systolic BP of 1.1 mm Hg (95% CI −0.2 to 2.3, p=0.086) and a slight reduction in diastolic BP of 0.8 mm Hg (95% CI −1.6 to 0.1, p=0.083), although the results were not statistically significant. There was some evidence of an increase in systolic BP in patients using CPAP &lt;4 h/night (1.5 mm Hg, 95% CI −0.0 to 3.1, p=0.052) and reduction in diastolic BP in patients using CPAP &gt;4 h/night (−1.4 mm Hg, 95% CI −2.5 to −0.4, p=0.008). CPAP treatment reduced both subjective sleepiness (p&lt;0.001) and OSA severity (p&lt;0.001). <h3>Interpretation</h3> Although CPAP treatment reduces OSA severity and sleepiness, it seems not to have a beneficial effect on BP in patients with minimally symptomatic OSA, except in patients who used CPAP for &gt;4 h/night.
Dynamics of Glomerular Ultrafiltration in the Rat V. RESPONSE TO ISCHEMIC INJURY
Authors: Terrance M. Daugharty, Iris F. Ueki, Paul F. Mercer, Barry M. Brenner
Journal: Journal of Clinical Investigation (1974)

An experimental model of postischemic, acute renal failure has been developed in Wistar rats with surface glomeruli, thereby making possible a direct assessment of the mechanisms responsible for the fall in glomerular filtration rate that characterizes this disorder. Whole kidney and cortical single nephron filtration rates were reduced proportionately, on average by approximately 40%, after 3 h of nearly complete occlusion of the ipsilateral renal artery. The possibility of a significant transtubular leak of inulin was excluded. This decline in filtration rate occurred in the absence of measured changes in mean arterial pressure, mean glomerular transcapillary hydrostatic pressure, or net ultrafiltration pressure at afferent and efferent ends of the glomerular capillary. Net ultrafiltration pressure at the efferent end of the capillary approached zero both before and after ischemic injury, demonstrating that filtration pressure equilibrium was achieved throughout this study. Single nephron filtration fraction remained unchanged, indicating that the fall in filtration rate was accompanied by a proportional decline in glomerular plasma flow. The results indicate that the fall in filtration rate was solely the consequence of this fall in glomerular plasma flow. Since filtration rate per nephron is equal to the product of the ultrafiltration coefficient and mean ultrafiltration pressure, this product must also have fallen in proportion to the decline in glomerular plasma flow. Evidence is presented to indicate that a change in ultrafiltration coefficient is not required to account for the observed fall in filtration rate. The reduction in glomerular plasma flow, occuring in the absence of a concomitant decline in mean glomerular capillary hydrostatic pressure, resulted from large and proportional increases in afferent and efferent arteriolar resistances. These resistance changes appear to play a fundamental role in the pathogenesis of this form of acute renal failure.
Doxorubicin and Paclitaxel-Loaded Lipid-Based Nanoparticles Overcome Multidrug Resistance by Inhibiting P-Glycoprotein and Depleting ATP
Authors: Xiaowei Dong, Cynthia A. Mattingly, Michael T. Tseng, Moo J. Cho, Yang Liu, Val R. Adams, Russell J. Mumper
Journal: Cancer Research (2009)

To test the ability of nanoparticle formulations to overcome P-glycoprotein (P-gp)-mediated multidrug resistance, several different doxorubicin and paclitaxel-loaded lipid nanoparticles were prepared. Doxorubicin nanoparticles showed 6- to 8-fold lower IC(50) values in P-gp-overexpressing human cancer cells than those of free doxorubicin. The IC(50) value of paclitaxel nanoparticles was over 9-fold lower than that of Taxol in P-gp-overexpressing cells. A series of in vitro cell assays were used including quantitative studies on uptake and efflux, inhibition of calcein acetoxymethylester efflux, alteration of ATP levels, membrane integrity, mitochondrial membrane potential, apoptosis, and cytotoxicity. Enhanced uptake and prolonged retention of doxorubicin were observed with nanoparticle-based formulations in P-gp-overexpressing cells. Calcein acetoxymethylester and ATP assays confirmed that blank nanoparticles inhibited P-gp and transiently depleted ATP. I.v. injection of pegylated paclitaxel nanoparticles showed marked anticancer efficacy in nude mice bearing resistant NCI/ADR-RES tumors versus all control groups. Nanoparticles may be used to target both drug and biological mechanisms to overcome multidrug resistance via P-gp inhibition and ATP depletion.
A novel mobile element inserted in the alpha spectrin gene: spectrin dayton. A truncated alpha spectrin associated with hereditary elliptocytosis.
Authors: H Hassoun, T L Coetzer, J N Vassiliadis, K E Sahr, G J Maalouf, S T Saad, L Catanzariti, J Palek
Journal: Journal of Clinical Investigation (1994)

Nonviral retrotransposons, retropseudogenes, and short interspersed nuclear elements (SINEs) are mobile DNA segments capable of transposition to new genomic locations, where they may alter gene expression. De novo integration into specific genes has been described in both germ and somatic cells. We report a family with hereditary elliptocytosis and pyropoikilocytosis associated with a truncated alpha-spectrin protein. We present the biochemical characteristics of this abnormal protein and show that the alpha-spectrin gene is disrupted by a mobile element resulting in exon skipping. This element causes duplication of the insertion site and is terminated by a long poly-A tail downstream of multiple consensus polyadenylation signals. Southern blot analysis of human genomic DNA, using this element as probe, reveals one to three copies per individual. This element has no homology to any previously reported sequence and therefore appears to be a member of a novel family of mobile elements.
Clearance of circulating DNA-anti-DNA immune complexes in mice.
Authors: W Emlen, M Mannik
Journal: The Journal of Experimental Medicine (1982)

DNA-anti-DNA immune complexes, produced from single-stranded DNA and IgG from a patient with systemic lupus erythematosus were cleared from the circulation of normal mice extremely rapidly, at a rate similar to the clearance of DNA alone. The initial clearance of these complexes was more rapid than the clearance of aggregated IgG, a surrogate immune complex containing a comparable number of IgG molecules, suggesting that the antigen (DNA) in the complexes significantly altered the clearance kinetics of the complexes. Analysis of the late clearance component of these complexes showed that anti-DNA is released back into the circulation after initial removal, and is then cleared at a rate similar to monomeric IgG. Whether this anti-DNA represents free antibody, or antibody bound to small nuclease digested DNA fragments, awaits further study.
Coronary Artery Bypass Grafting Using the Radial Artery
Authors: Robert F. Tranbaugh, Kamellia R. Dimitrova, Patricia Friedmann, Charles M. Geller, Loren J. Harris, Paul Stelzer, Bertram M. Cohen, Wilson Ko, Helbert DeCastro, David Lucido, Darryl M. Hoffman
Journal: Circulation (2012)

Radial artery (RA) grafts are an attractive second arterial conduit after the left internal thoracic artery (LITA) for coronary artery bypass graft (CABG) surgery. However, long-term outcomes and the need for subsequent reintervention have not been defined.We performed a retrospective cohort study of our single institution's 16-year experience with 1851 consecutive patients (average age, 58 years; 82% men, 36% diabetic) undergoing primary, isolated CABG with the LITA, RA, and saphenous vein as needed. Average grafts per patient were 3.8, with 2.4 arterial grafts per patient. Survival was determined using the Social Security Death Index. Grafts were nonpatent if they had a >50% stenosis, a string sign, or were occluded. Five patients (0.3%) died in hospital and 0.8% had a myocardial infarction, 1.1% a stroke, and 0.6% renal failure. Kaplan-Meier-estimated 1-, 5-, 10-, and 15-year survival was 99%, 96%, 89%, and 75%, respectively. Of the cohort, 278 symptomatic patients underwent cardiac catheterization at our institution an average of 5.0±3.8 years (range, 0.1-12 years) after CABG. Overall RA (n=420 grafts) patency was 82% and SV (n=364 grafts) patency, 47% (P<0.0001). LITA (n=287 grafts including 9 sequential grafts) patency was 85% and right internal thoracic artery (n=15 grafts) patency was 80% (P=0.6). RA patency was not different from LITA patency (P=0.3). Overall freedom from catheterization, percutaneous coronary intervention, and CABG was 85%, 97%, and 99%, respectively.RA grafting is a highly effective revascularization strategy providing excellent short and long-term outcomes with very low rates of reintervention. RA patency is similar to LITA patency and is much better than SV patency. RA grafting should be more widely utilized in patients undergoing CABG.
Nuclear localisation of p65 in sputum macrophages but not in sputum neutrophils during COPD exacerbations
Authors: G Caramori
Journal: Thorax (2003)

Exacerbations represent an important feature of the clinical manifestation and natural history of chronic obstructive pulmonary disease (COPD). Nuclear localisation of p65 is a signal of nuclear factor-kappaB (NF-kappaB) activation. A study was undertaken to evaluate whether NF-kappaB activation is modified in sputum cells during COPD exacerbations.Total and nuclear p65 immunoreactivity was measured by immunocytochemistry in the sputum cells of 11 smokers with moderate COPD during an exacerbation and after 6-8 weeks of clinical stability.Total sputum cell count was significantly increased during exacerbations from a median (IQR) of 880 (510-1865) to 1914.5 (1065-3205) x 10(3)/ml (p<0.05). The main inflammatory cells in the sputum were neutrophils (83.2 (75.4-92.3)%) and macrophages (14.7 (2.6-21.6)%) and their relative proportion did not change during exacerbations. Nuclear staining for p65 was absent in sputum neutrophils, both during exacerbations and in the stable phase. In contrast, the percentage of macrophages expressing nuclear p65 increased significantly during exacerbations from a median (IQR) of 16 (7-24)% to 41.4 (6-69)% (p<0.05).NF-kappaB appears to be activated in sputum macrophages but not in sputum neutrophils during exacerbations of COPD
The interferon gamma receptor 1 (IFNGR1) -56C/T gene polymorphism is associated with increased risk of early gastric carcinoma
Authors: P Canedo, G Corso, F Pereira, N Lunet, G Suriano, C Figueiredo, C Pedrazzani, H Moreira, H Barros, F Carneiro, R Seruca, F Roviello, J C Machado
Journal: Gut (2008)

<h3>Background and aim:</h3> It has been demonstrated that polymorphisms within inflammation-related genes are associated with the risk of gastric carcinoma (GC) in people infected with <i>Helicobacter pylori</i>. Recently, polymorphisms in the gene encoding the interferon gamma receptor 1 (<i>IFNGR1</i>) were found to be associated with increased susceptibility to <i>H pylori</i> infection. We aimed to determine the association between polymorphisms in the <i>IFNGR1</i> gene and development of chronic gastritis and GC. <h3>Methods:</h3> In a case–control study including 733 controls, 213 patients with chronic gastritis and 393 patients with GC, the <i>IFNGR1</i> −611*G/*A, −56*C/*T, +1004*A/*C and +1400*T/*C polymorphisms were genotyped. A second independent case–control study including 100 controls and 65 patients with GC was used for confirmation of the original results. The effect of the −56*C/*T promoter polymorphism in the level of expression of the <i>IFNGR1</i> gene was evaluated by an <i>IFNGR1</i> −56*C/*T allele specific luciferase reporter assay. <h3>Results:</h3> In patients with early onset GC (defined as being less than 40 years of age at the time of diagnosis) we found a significant over-representation of the <i>IFNGR1</i> −56*T/*T homozygous genotype with an odds ratio (OR) of 4.1 (95% confidence interval (CI) 1.6 to 10.6). This result was confirmed in a second independent case–control study. In the luciferase reporter assay we observed a 10-fold increase (p&lt;0.001) in luciferase expression associated with the <i>IFNGR1</i>−56*T allele. <h3>Conclusions:</h3> Our results indicate that the <i>IFNGR1</i> −56C/T polymorphism is a relevant host susceptibility factor for GC development. Our data also indicate that this genetic polymorphism is functionally relevant and may be related to the early development of GC.
RANDOMISED CONTROLLED TRIAL OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR VERSUS UROKINASE IN THE TREATMENT OF ACUTE PULMONARY EMBOLISM
Authors: SamuelZ. Goldhaber, John Heit, G.V.R.K. Sharma, J.Stevan Nagel, Ducksoo Kim, J.Anthony Parker, David Drum, Kathleen Reagan, James Anderson, CraigM. Kessler, John Markis, Douglas Dawley, Michael Meyerovitz, DouglasE. Vaughan, SabahS. Tumeh, Joseph Loscalzo, AndrewP. Selwyn, Eugene Braunwald
Journal: The Lancet (1988)