tbuckley/cabot-search huggingface dataset:
The Central Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Septic Pathogen Lipid Transport and Clearance
Authors: Keith R. Walley, Gordon A. Francis, Steven M. Opal, Evan A. Stein, James A. Russell, John H. Boyd
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Microbial cell walls contain pathogenic lipids, including LPS in gram-negative bacteria, lipoteichoic acid in gram-positive bacteria, and phospholipomannan in fungi. These pathogen lipids are major ligands for innate immune receptors and figure prominently in triggering the septic inflammatory response. Alternatively, pathogen lipids can be cleared and inactivated, thus limiting the inflammatory response. Accordingly, biological mechanisms for sequestering and clearing pathogen lipids from the circulation have evolved. Pathogen lipids released into the circulation are initially bound by transfer proteins, notably LPS binding protein and phospholipid transfer protein, and incorporated into high-density lipoprotein particles. Next, LPS binding protein, phospholipid transfer protein, and other transfer proteins transfer these lipids to ApoB-containing lipoproteins, including low-density (LDL) and very-low-density lipoproteins and chylomicrons. Pathogen lipids within these lipoproteins and their remnants are then cleared from the circulation by the liver. Hepatic clearance involves the LDL receptor (LDLR) and possibly other receptors. Once absorbed by the liver, these lipids are then excreted in the bile. Recent evidence suggests pathogen lipid clearance can be modulated. Importantly, reduced proprotein convertase subtilisin/kexin type 9 activity increases recycling of the LDLR and thereby increases LDLR on the surface of hepatocytes, which increases clearance by the liver of pathogen lipids transported in LDL. Increased pathogen lipid clearance, which can be achieved by inhibiting proprotein convertase subtilisin/kexin type 9, may decrease the systemic inflammatory response to sepsis and improve clinical outcomes.
Bone marrow transplantation for myelodysplasia and secondary acute nonlymphoblastic leukemia.
Authors: G Longmore, E C Guinan, H J Weinstein, R D Gelber, J M Rappeport, J H Antin
Journal: Journal of Clinical Oncology (1990)

Twenty-three patients with primary myelodysplasia (MDS) or secondary myelodysplasia/acute nonlymphocytic leukemia (MDS/ANLL) were treated with allogeneic or syngeneic bone marrow transplantation (BMT). Only one patient was in a chemotherapy-induced hematologic remission. Graft-versus-host disease prophylaxis included methotrexate, methotrexate plus cyclosporine, cyclosporine, or T-cell depletion using one of two anti-CD5 monoclonal antibodies. For patients with primary MDS, the median age was 19 years (range, 11 to 41 years) and the actuarial disease-free survival was 56% +/- 21% (median follow-up, 2 years; range, 0.8 to 5 years). There were three graft failures (two with autologous recovery) and two early deaths. Outcome appeared to be related to French-American-British (FAB) classification. For patients with secondary MDS/ANLL, the median age was 28 years (range, 3 to 16 years) and the actuarial disease-free survival was 27% +/- 13% (median follow-up, 5 years; range, 2.5 to 8.5 years). There were no graft failures, two relapses, and four early deaths. The presence of marrow fibrosis per se did not predict for graft failure (P = .21); however, the use of T-cell depleted marrow in patients with marrow fibrosis resulted in graft failure in three of five individuals. Our results suggest that in patients with primary MDS or secondary MDS/ANLL, BMT should be considered early in the course of the disease, and that attempts at inducing a remission prior to BMT appeared to be unnecessary. In MDS patients with marrow fibrosis, T-cell depletion should be avoided.
Phase II Study of Docetaxel, Estramustine, and Low-Dose Hydrocortisone in Men With Hormone-Refractory Prostate Cancer: A Final Report of CALGB 9780
Authors: D.M. Savarese, S. Halabi, V. Hars, W.L. Akerley, M-E Taplin, P.A. Godley, A. Hussain, E.J. Small, N.J. Vogelzang
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To investigate the combination of docetaxel, estramustine (EM), and low-dose hydrocortisone in men with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Combinations of EM with other antimitotic agents such as docetaxel are synergistic in vitro and show significant clinical activity in patients with HRPC. We studied intravenous administration of docetaxel 70 mg/m 2 , oral estramustine, and low-dose daily hydrocortisone in men with HRPC who demonstrated progression after initial hormone therapy. RESULTS: Of the 47 men enrolled onto this multicenter cooperative group study, 46 were assessable for response and/or toxicity. In the 24 patients with measurable disease, there were three complete and nine partial responses for a measurable disease response rate of 50% (12 of 24 patients; 95% confidence interval [CI], 27% to 73%). In the 44 patients in whom pretreatment prostate-specific antigen (PSA) was elevated, 30 (68%) had a 50% or greater decrease, and 25 (57%) had a 75% or greater decrease in PSA. The combined measurable disease and biochemical response rate in all 46 assessable patients was 54% (three complete responses, 22 partial responses, 95% CI, 37% to 71%). The predominant toxicity was neutropenia, with 26% of patients having grade 3 and 30% having grade 4 granulocytopenia; there were no episodes of febrile neutropenia. Other common but mild adverse effects included malaise/fatigue, peripheral edema, and hyperglycemia. The incidence of thromboembolic events during therapy was 9%. With a median follow-up of 17 months, the median survival was 20 months. The median time to disease progression was 8 months for all patients, and 10 months for those with measurable disease. CONCLUSION: This therapy is efficacious and moderately well tolerated in HRPC and should be compared in a phase III trial with mitoxantrone and prednisone.
Are air pollutants confounders in relation to weather variables as triggers for acute asthma
Authors: Caroline Gouder, Eleanor Gerada, Josef Micallef, Simon Gouder, Richard Pullicino, Stephen Montefort
Journal: European Respiratory Journal (2013)

Background: Previous results from our study show that emergency department (ED) visits for acute asthma exhibit seasonality in Malta. Visits were positively correlated with wind speed and precipitation and negatively correlated with humidity, barometric pressure and temperature.  Aim: To identify whether air pollutants are confounders in relation to weather variables.  Methodology: All adults (n=328) presenting to the ED with acute asthma in 2010 were included. Daily weather data was obtained from the meteorological office. Daily ambient levels of PM2.5, PM10, SO2 and O3 were obtained from MEPA. The day prior to and that of presentation were taken to be -1 and 0 respectively.  Results: On days of increased ED visits: high wind speed was positively correlated with SO2 and O3 on day 0 and -1(p 0.05); increased precipitation was negatively correlated with PM2.5, PM10, SO2 and O3 on day 0 and -1(p 0.05); barometric pressure was positively correlated with O3(p 0.05). Regression analysis showed temperature to be the best predictor for ED visits(p  Conclusion:High wind speeds and temperature are associated with elevated air pollutant levels. Precipitation, humidity and pressure seem to be independent triggers for acute asthma. Increased vigilance during such periods may avoid exacerbations.
Differences in the recommended initial therapy of COPD according to GOLD guidelines 2006 and 2011
Authors: Ivan Vyshnyvetskyy, Yuriy Mostovoy, Olexiy Onyshchenko
Journal: European Respiratory Journal (2012)

Background.  The last GOLD Guideline revision was released in late 2011. We hypothesized that newer GOLD guidelines would frequently lead to a differnent initital treatment choice.   Aims and objectives . To demonstrate the magnitude of difference in recommended initial treatments in COPD patients based on past and recent GOLD revisions.   Methods . We retrospectively analyzed 52 patients with first diagnosed stable COPD. Spirometry, COPD Assessment Test and evaluation of exacerbations were done. Patients were allocated to the most appropriate treatment according to GOLD 2006 and 2011 management scheme.   Results.  According to GOLD 2006 criteria 32 (61,5%), 18 (34,6%) and 2 (3,8%) patients were stage II, III and IV, respectively. Forty (76,9%) patients should be prescribed monotherapy with LABA or LAMA and 12 (23,1%) required ICS/LABA therapy. According to GOLD 2011 6 (11,5%), 19 (36,5%), 2 (3,8%) and 25 (48,1%) patients were Group A, B, C and D, respectively. Thus, 6 (11,5%) patients would not be prescribed long-acting bronchodilators (BD) as initial therapy, 20 (38,5%) patients required monotherapy with long-acting BD and 26 (50,0%) required therapy with ICS/LABA. In accordance with GOLD 2011 treatment scheme, initial therapy was required to be changed in 21 (40,4%) patients (13 (40,6%) stage II and 8 (40,0%) stage III-IV). In 6 (11,5%) cases we had to administer more “light” therapy (with short-acting BD instead of long-acting BD), and 14 (26,9%) patient required more intensive treatment, usually LABA/ICS instead of monotherapy.   Conclusions.  In significant proportion of COPD patients GOLD 2011 treatment scheme leads to another, generally more intensive, initial treatment.
Wheelchair Use: A Physical Sign in Gastroenterological Practice
Authors: E Chiotakakou-Faliakou, U Dave, A Forbes
Journal: Journal of the Royal Society of Medicine (1996)

Diagnosis of functional abdominal pain requires exclusion of organic causes, and many patients undergo considerable investigation. A positive physical sign supporting a functional diagnosis could therefore be of benefit. Wheelchair use specifically for abdominal symptoms was suspected to represent such a sign. Review of 300 consecutive new referrals to a gastroenterology clinic revealed 10 wheelchair users. In four women the chair was used because of the abdominal condition. The final diagnosis (with follow-up to at least 12 months) was functional abdominal pain in each of these cases. All four had had surgery without symptom relief, and all had used their chairs intermittently (mainly for social occasions and hospital visits) for at least 12 months. They believed that normal walking was rendered impossible by abdominal pain whereas the other six wheelchair users gave a clear account of lower limb pain or weakness. Secondary gain with reinforcement of the ‘sick role’ was felt to be the probable explanation for wheelchair use in the former group. Wheelchair attendance at the gastroenterology clinic, in the absence of lower limb symptoms, is a rare observation but one that may usefully be added to criteria for diagnosis of a functional disorder.
Inhibiting effects of tiotropium bromide on neocollagenesis during 6 month treatment
Authors: Mykola Ostrovskyy, Oleksandr Varunkiv, Mariana Kulynych-Miskiv, Iryna Savelikhina
Journal: European Respiratory Journal (2011)

Background:  Chronic obstructive pulmonary disease (COPD) is one of the most important causes of morbidity and mortality worldwide, which are the third most common cause of death (8%) in the 25 member states of the European Union.   Purpose of the study:  Is the evaluation of type IV collagen dynamic in bronchoalveolar lavage (BAL) during the treatment with tiotropium bromide.   Materials and methods:  The content of type IV collagen was investigated in BAL of 43 patients with stage 2 COPD before and after 1, 3 and 6 months of treatment with tiotropium bromide using ELISA.   Results of the study:  The content of type IV collagen in BAL on a moment of hospitalization in patients with COPD exacerbation was (61,14±1,28) ng/ml that is in 6.19 times (p   Conclusions:  The reduction of type IV collagen content in BAL under tiotropium bromide treatment during 6 month is a clear evidence of inhibiting effects of tiotropium bromide on neocollagenesis
Characterisation of Orientia tsutsugamushi genotypes from wild rodents and chigger mites in Korea
Authors: S.-K. Shim, E.-N. Choi, K.-O. Yu, H.-J. Park, C.-M. Kim, K.-H. Lee, J.-K. Park, P.-H. Park, M.-H. Yoon, S.-H. Park, Y.-S. Choi, K.-J. Hwang, M.-Y. Park
Journal: Clinical Microbiology and Infection (2009)
Binding and transfer of verocytotoxin by polymorphonuclear leukocytes in hemolytic uremic syndrome
Authors: D. Maroeska W. M. te Loo, Leo A. H. Monnens, Thea J. A. M. van der Velden, Mario A. Vermeer, Frank Preyers, Pierre N. M. Demacker, Lambertus P. W. J. van den Heuvel, Victor W. M. van Hinsbergh
Journal: Blood (2000)
Which BAL fluid (BALF) analyses are clinically useful in immunocomptent children
Authors: Stéphanie Govindoorazoo, Stephane Debelleix, Philippe Reix, Stéphanie Bui, Vincent Boisserie-Lacroix, Michael Fayon
Journal: European Respiratory Journal (2013)

Introduction:  During a bronchoscopic procedure, systematic BALF analyses are often performed (cell types, lipid-laden macrophages LLM, haemosiderin-laden alveolar macrophages HLAM, lymphocyte subsets, bacteria, atypical bacteria, viruses, fungi, parasites) irrespective of the baseline clinical condition.   Aim:  To determine 1) which BALF laboratory analyses are  not  useful for the management of immunocompetent children with common chest diseases, 2) the cost reduction induced by the abolition of such analyses.   Methods:  A two-centre (Bordeaux and Lyon) retrospective study including children aged    Results:  333 bronchoscopies were performed in 169 children (mean age, 3.6 yrs (IQR 1.3-6.1); M:F = 1:1.35): rRTI = 66 patients (39%), DA=50(30%), CC=22(13%), A=26(15%), and ILD=5(3 %).  For each BALF analysis, 20 % of the original cost may have been saved in all cases, reaching 62% of the original cost had stringent criteria been applied.   Conclusion:  In immunocompetent children with common respiratory disorders, cell counts/bacterial cultures are indicated. Investigations for fungi and parasites are unnecessary. Analyses regarding LLM, HLAM, atypical bacteria and viruses should not be carried out systematically.
Glycation of Fetal Hemoglobin Reflects Hyperglycemia Exposure In Utero
Authors: Felix O. Dupont, Marie-France Hivert, Catherine Allard, Julie Ménard, Patrice Perron, Luigi Bouchard, Julie Robitaille, Jean-Charles Pasquier, Christiane Auray-Blais, Jean-Luc Ardilouze
Journal: Diabetes Care (2014)

The lifetime risk of metabolic diseases in offspring of women with gestational diabetes mellitus (GDM) depends, at least in part, on the impact of glycemic fetal programming. To quantify this impact, we have developed and validated a unique mass spectrometry method to measure the percentage of glycated hemoglobin in cord blood.This case-control study includes 37 GDM women and 30 pregnant women with normal glucose tolerance (NGT).Glycation of the α-chain (Glα) was higher in neonates from GDM (2.32 vs. 2.20%, P < 0.01). Glα strongly correlated with maternal A1C measured at delivery in the overall cohort (r = 0.67, P < 0.0001) as well as in each group (GDM: r = 0.66, P < 0.0001; NGT: r = 0.50, P = 0.01).Thus, Glα may reflect hyperglycemic exposure during the last weeks of fetal development. Future studies will confirm Glα is a predictive biomarker of prenatally programmed lifetime metabolic health and disease.
e.cigarette, a product for tobacco initiation also experimented by non-smokers among Parisian teenagers
Authors: Bertrand Dautzenberg, Maryvonne Noël, Pierre Birkui, Joseph Osman, Marie-Dominique Dautzenberg
Journal: European Respiratory Journal (2013)

e.cigarettes become popular in France. This new product attract non-only heavy tobacco smokers, but also teenagers due to a price decrease from more than 100 € to less than 6 € for the disposable e.cigarettes. We explore how much this product could become an instrument of cigarette initiation in teenager’s users or not of tobacco.  Method: A question regarding e.cigarettes has been introduced in the annual survey by auto questionnaire conducted since 1991 by PST with school authorities on a 2% random sample among 11-19-year-old teenagers.  Results: Among 3409 teenagersfrom 12 to 19 years, questioned in 2012, 49% were girls, mean age is 15.34 years. The rate of daily smokers and occasional smokers is 4.2% and 16.8% among the 12-15-year-old and 21.3% and 10.4% among the 16-19-year-old teenagers.  The percentage of teenagers reporting experimentation of e.cigarettes is 6% from 12-14-year-old, 12% among 15-16-year-old, 19% among 17 years old, drops down to 12% for the 18-year-old and to 6% for the 19-year-old.  Until the age of 17, girls had more experienced e.cigarette than the boys.  The experimentation varies according to smoking status: 5% among non-smokers, 15% among occasional smokers, 18% among ex-smokers and 33% among regular smokers has experienced e.cigarettes. The experimentation rate of e.cigarettes is 23% among smokers who don’t plan to quit and 19% among those who plan to quit.  Conclusion: The e.cigarettes had become a familiar product to young teenagers, mostly aged between 14-17 years (10.6% in girls vs. 9.1% in boys). To prevent this initiation, we recommend regulating e.cigarettes to forbid any promotion and sale to teenagers under 18.
Abstract 205: Mitochondrial Sirt3 Is Upregulated By Glucagon-like Peptide-1 Receptor Activation And Contributes To Reversal Of Cardiac Mitochondrial Remodeling Induced By Type 2 Diabetes.
Authors: Akio Monji, Yasuko K Bando, Haruya Kawase, Morihiko Aoyama, Toyoaki Murohara
Journal: Circulation Research (2014)

RATIONALE: Sirtuin 3 (SIRT3) is a mitochondrial protein deacetylase that maintains basal ATP yield and its expression level is increased by fasting, exercise, and some NAD+ intermediates. We recently reported that the glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 (Ex-4) ameliorated cardiac mitochondrial remodeling in diabetic cardiomyopathy via increase in cardiac cyclic AMP (AJP2013). Because changes in cyclic AMP level is regulated by adenylyl cyclase which is one of the downstream target of Ex-4, we hypothesized that SIRT3 may involve in the Ex-4-mediated myocardial reverse remodeling of mitochondria in diabetic mice. METHODS: Type 2 diabetic Mice (16-week old male) were allocated into experimental groups as follows: Ex-4 (24 nmole/kg/day, subcutaneously administrated by osmotic pump for 40 days, DIO/Ex-4) and vehicle control (DIO/CON). Heart samples and cultured rat neonatal cardiomyocytes were subjected to mitochondrial fractionation using density gradient. RESULTS: Cardiac cyclic AMP concentration and phosphorylation of CREB were elevated in DIO-ex4, suggesting successful administration of Ex-4. Electron microscopic analysis revealed that Ex-4 reversed destroyed cristae structure and defragmented mitochondria of DIO/CON heart. The ratio of expression levels of Mitofusin-1 (Mfn1) and mitofusin-2 (Mfn2) was consistently suppressed by Ex-4 treatment, suggesting normalization of mitochondrial morphology. Of note, DIO-CON exhibited marked decrease in cardiac SIRT3 level compared to lean/nondiabetic counterpart, which was reversed by exendin-4 treatment. Pharmacological production of intracellular cAMP levels (Isoprotelenol (10 microM) and 8-bromo-cyclic AMP (1 mM)) increased SIRT3 mRNA in cultured primary cardiomyocytes. The AMP-activated protein kinase (AMPK) inhibitition blocked the increase in SIRT3 mRNA, indicating that the SIRT3 expression was regulated by AMPK-dependent manner. CONCLUSIONS: Our results indicate that Ex-4 reversed abnormal suppression of SIRT3 in mitochondria via activating the PKA/AMPK-dependent pathway.
Abstract 18974: Rhythm Control with Catheter Ablation Improves Cardiomyopathy and Heart Failure Compared with Rate Control
Authors: Umashankar Lakshmanadoss, Amrish Deshmukh, Gunjan Choudhary, Pramod Deshmukh
Journal: Circulation (2014)

Introduction: Role of rhythm control in addition to rate control, in patients with atrial fibrillation and heart failure reduced EF (HFrEF) is unknown. Objective: We sought to compare catheter ablation with rate control in patients with AF and HFrEF. Methods: Ninety patients with AF and LVEF &lt; 40 % underwent pulmonary vein isolation with or without substrate modification. Follow-up included Holter monitoring and echocardiography at baseline, 3 months and at 6 months. A propensity-matched group of 80 patients with AF and LVEF &lt;40% treated with rate control was used for comparison. Post-matching weighted linear regression analysis was used to compare outcomes. Results: At 6 months, 64% of patients who underwent ablation remained in sinus rhythm. Average heart rate (HR) was similar between groups at baseline and follow up. (79 ± 14.5 to 76 ± 7.7 in ablation group and 82.4 ±8.9 to 78.3 ± 8.8 in rate control group). LVEF significantly improved in patients who underwent ablation (30.9 ± 8.6 to 43.4 ±10.9) compared with no change in patients who were rate controlled (to 25.8 ±19.3 to 25.2 ±6.64) (p=2E-16). NHYA class improved from 2.26 ±0.44 to 1.62 ±0.64 with ablation compared to 2.4 ±0.5 to 2.24 ±0.44 with rate control but did not reach statistical significance. Patients who remained in AF after ablation had minimal change in LVEF and NHYA class. No procedural complications noted. Conclusions: In patients with AF, HFrEF, and adequate HR control, rhythm control by catheter ablation improved LVEF compared with a propensity matched group of patients treated with rate control. Rhythm control with catheter ablation may be considered in patients with AF and HF who are adequately rate controlled
3-Methylcholanthrene: Transient Inhibition of the Lytic Step of Mouse Natural Killer Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: T Kalland, J G Forsberg
Journal: JNCI Journal of the National Cancer Institute (1983)

Female mice belonging to NMRI stock were inoculated neonatally with daily doses of 5 micrograms diethylstilbestrol (DES) or olive oil for the first 5 days after birth and in adult life with 20 or 100 micrograms 3-methylcholanthrene (MCA) or the vehicle tricaprylin only. The cytotoxic activity of spleen natural killer (NK) cells against YAC-1 target cells was studied in a 51Cr release assay at 2, 5, 10, or 15 days after the MCA injection. A dose of 20 micrograms MCA to neonatally olive oil-injected females did not influence the NK activity, whereas an injection of 100 micrograms MCA significantly depressed the NK activity to about half the value seen in controls. This suppression was transient, and the normal level was reached again 15 days after the injection. The depressed NK activity could not be related to humoral or cellular suppressor mechanisms. A study at the single-cell level revealed that the inhibition was due to interference with the lytic step of the NK cell without affecting target-binding capacity. In vitro exposure of spleen cells from MCA-treated animals to interferon fully restored the NK activity. Neonatal DES treatment resulted in a depressed NK activity in adult females to a level about half of that seen in olive oil-injected controls. The NK activity in DES-treated females was not influenced by either 20 or 100 micrograms MCA. The MCA-induced suppression of NK activity was discussed in relation to the earlier reported difference in incidence of MCA-induced sarcomas between DES-treated and control females after they were given 20 micrograms MCA in adult life, as well as in relation to the same incidence in the 2 groups treated with 100 micrograms MCA. The results are compatible with a significant role for NK cells during MCA carcinogenesis and indicate that a possible part of the tumorigenic effect of MCA is its early suppressive effect on NK cell activity.