bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of acute graft-versus-host disease by microRNA-155
Authors: Ranganathan Parvathi , Heaphy Catherine E. A. , Costinean Stefan , Stauffer Nicole , Na Caroline , Hamadani Mehdi , Santhanam Ramasamy , Mao Charlene , Taylor Patricia A. , Sandhu Sukhinder , He Gang , Shana'ah Arwa , Nuovo Gerard J. , Lagana Alessandro , Cascione Luciano , Obad Susanna , Broom Oliver , Kauppinen Sakari , Byrd John C. , Caligiuri Michael , Perrotti Danilo , Hadley Gregg A. , Marcucci Guido , Devine Steven M. , Blazar Bruce R. , Croce Carlo M. , Garzon Ramiro 
Published: March 2012

Abstract
Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic stem cell transplant (alloHSCT), underscoring the need to further elucidate its mechanisms and develop novel treatments. Based on recent observations that microRNA-155 (miR-155) is up-regulated during T-cell activation, we hypothesized that miR-155 is involved in the modulation of aGVHD. Here we show that miR-155 expression was up-regulated in T cells from mice developing aGVHD after alloHSCT. Mice receiving miR-155–deficient donor lymphocytes had markedly reduced lethal aGVHD, whereas lethal aGVHD developed rapidly in mice recipients of miR-155 overexpressing T cells. Blocking miR-155 expression using a synthetic anti–miR-155 after alloHSCT decreased aGVHD severity and prolonged survival in mice. Finally, miR-155 up-regulation was shown in specimens from patients with pathologic evidence of intestinal aGVHD. Altogether, our data indicate a role for miR-155 in the regulation of GVHD and point to miR-155 as a novel target for therapeutic intervention in this disease.
Stem cell heterogeneity: implications for aging and regenerative medicine
Authors: Muller-Sieburg Christa E. , Sieburg Hans B. , Bernitz Jeff M. , Cattarossi Giulio 
Published: March 2012

AbstractFor decades, hematopoietic stem cells (HSCs) were thought to be a homogeneous population of cells with flexible behavior. Now a new picture has emerged: The HSC compartment consists of several subpopulations of HSCs each with distinct, preprogrammed differentiation and proliferation behaviors. These programs are epigenetically fixed and are stably bequeathed to all daughter HSCs on self-renewal. HSCs within each subset are remarkably similar in their self- renewal and differentiation behaviors, to the point where their life span can be predicted with mathematical certainty. Three subsets can be distinguished when HSCs are classified by their differentiation capacity: myeloid-biased, balanced, and lymphoid-biased HSCs. The relative number of the HSC subsets is developmentally regulated. Lymphoid-biased HSCs are found predominantly early in the life of an organism, whereas myeloid-biased HSCs accumulate in aged mice and humans. Thus, the discovery of distinct subpopulations of HSCs has led to a new understanding of HCS aging. This finding has implications for other aspects of HSC biology and applications in re-generative medicine. The possibility that other adult tissue stem cells show similar heterogeneity and mechanisms of aging is discussed.
MYC + diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation
Authors: Cuccuini Wendy , Briere Josette , Mounier Nicolas , Voelker Hans-Ullrich , Rosenwald Andreas , Sundstrom Christer , Cogliatti Sergio , Hirchaud Edouard , Ysebaert Loic , Bron Dominique , Soulier Jean , Gaulard Philippe , Houlgatte Remi , Gisselbrecht Christian , Thieblemont Catherine 
Published: March 2012

AbstractApproximately 5-10% of diffuse large B-cell lymphomas (DLBCL) harbor a 8q24/MYC rearrangement (MYC+). We determined the prognostic significance of MYC rearrangement in patients with relapsed/refractory DLBCL prospectively treated by R-ICE or R-DHAP followed by high-dose therapy and autologous stem cell transplantation. Twenty-eight (17%) of the 161 patients analyzed presented a MYC+ rearrangement, targeted as either simple hit (25%) or complex hits (n=75%) including MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6. Results were statistically highly concordant in matched primary and relapsed biopsies (n = 45). Compared to the MYC− DLBCL patients, the MYC+ DLBCL patients presented with a more elevated lactico-deshydrogenase level (P = .0006) and a more advanced age adjusted international prognostic index (P = .0039). The 4-year PFS and OS were significantly lower in the MYC+ DLBCL patients than those in the MYC− DLBCL patients, with rates of 18% vs 42% (P = .0322), and of 29% vs 62% (P = .0113), respectively. Type of treatment, R-DHAP or R-ICE, had no impact on survivals, with 4-year PFS rates of 17% vs 19% and 4-year OS rates of 26% vs 31%. In conclusion, MYC rearrangement is an early event in DLBCL. MYC+ DLBCL patients have a significant inferior prognosis than MYC− DLBCL patients. Their outcome was not influenced by the proposed salvage therapy.
Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era
Authors: Warlick Erica , Ahn Kwang Woo , Pedersen Tanya L. , Artz Andrew , de Lima Marcos , Pulsipher Michael , Akpek Gorgun , Aljurf Mahmoud , Cahn Jean-Yves , Cairo Mitchell , Chen Yi-Bin , Cooper Brenda , Deol Abhinav , Giralt Sergio , Gupta Vikas , Khoury H. Jean , Kohrt Holbrook , Lazarus Hillard M. , Lewis Ian , Olsson Richard , Pidala Joseph , Savani Bipin N. , Seftel Matthew , Socié Gerard , Tallman Martin , Ustun Celaettin , Vij Ravi , Vindeløv Lars , Weisdorf Daniel 
Published: March 2012

Abstract
Tyrosine kinase inhibitors (TKIs) and reduced intensity conditioning (RIC)/nonmyeloablative (NMA) conditioning hematopoietic cell transplants (HCTs) have changed the therapeutic strategy for chronic myelogenous leukemia (CML) patients. We analyzed post-HCT outcomes of 306 CML patients reported to the Center for International Blood and Marrow Transplant Research aged 40 years and older undergoing RIC/NMA HCT from 2001 to 2007: 117 (38%) aged 40 to 49 years, 119 (39%) 50 to 59 years, and 70 (23%) 60 years or older. The majority (74%) had treatment with imatinib before HCT. At HCT, most patients aged 40 to 49 years were in chronic phase (CP) 1 (74%), compared with 31% aged 60 years or older. Siblings were donors for 56% aged 40 to 49 years; older cohorts had more unrelated donors. The majority received peripheral blood grafts and RIC across all age groups. 3 year overall survival (54%, 52%, and 41%), day + 100 grade II-IV acute GVHD (26%, 32%, and 32%), chronic GVHD (58%, 51%, and 43%), and 1-year treatment-related mortality (18%, 20%, and 13%) were similar across ages. The 3-year relapse incidence (36%, 43%, and 66%) and disease-free survival (35%, 32%, and 16%) were inferior in the oldest cohort. Importantly, for CP1 patients, relapse and disease-free survival were similar across age cohorts. Allogeneic RIC HCT for older patients with CML can control relapse with acceptable toxicity and survival in TKI-exposed CML, especially if still in CP1.
A 3-year longitudinal study of sleep disordered breathing in the elderly
Authors: Sforza Emilia , Gauthier Maylis , Crawford-Achour Emilie , Pichot Vincent , Maudoux Delphine , Barthélémy Jean Claude , Roche Frédéric 
Published: March 2012

Limited and controversial data exist on the natural evolution of sleep disordered breathing (SDB) in untreated individuals. This study examines the evolution of SDB over a 3-yr period in a community-based sample of elderly subjects.From the initial cohort of 854 healthy subjects aged mean±sd68.4±0.8 yrs, 519 untreated subjects accepted clinical and instrumental follow-up 3.6±1.6 yrs later. SDB was defined as a respiratory disturbance index (RDI) >15 events·h−1.At baseline, 202 (39%) subjects had an RDI ≤15 events·h−1and 317 (61%) had an RDI >15 events·h−1. 3 yrs later, 280 (54%) subjects were non-SDB and 239 (46%) had SDB. Between evaluations, the RDI decreased from 22.3±16.2 to 16.4±13.0 events·h−1, with a greater decrease in the number of cases with an RDI >30 events·h−1that in those with RDI ≥30 events·h−1. In the non-SDB group, 81% had a stable RDI and 19% increased their RDI by a mean of 13.7 events·h−1. In the SDB group, the RDI decreased to values ≤15 events·h−1in 36.6% of cases, 63.4% still having SDB. The RDI changes did not depend on weight changes.In healthy elderly subjects, the prevalence and severity of SDB did not show a tendency toward natural worsening, some cases having improvement or a remission independent of weight changes. These findings also suggest that in the elderly, natural SDB progression is still hypothetical.
Does oxidative stress modulate limb muscle atrophy in severe COPD patients?
Authors: Fermoselle Clara , Rabinovich Roberto , Ausín Pilar , Puig-Vilanova Ester , Coronell Carlos , Sanchez Francisco , Roca Josep , Gea Joaquim , Barreiro Esther 
Published: March 2012

Oxidative stress may differentially regulate protein loss within peripheral muscles of severe chronic obstructive pulmonary disease (COPD) patients exhibiting different body composition.Oxidation levels of proteins, myosin heavy chain (MyHC) and myonuclei, superoxide anion, antioxidants, actin, creatine kinase, carbonic anhydrase-3, ubiquitin–proteasome system, redox-signalling pathways, inflammation and muscle structure, and damage were quantified in limb muscles of severe COPD patients with and without muscle wasting, and in sedentary controls.Compared with controls, in the quadriceps of muscle-wasted COPD patients, levels of protein carbonylation, oxidation of MyHC and myonuclei, superoxide anion production, superoxide dismutase, total protein ubiquinitation, E214k, atrogin-1, FoxO1 and p65 were higher, while content of MyHC, creatine kinase, carbonic anhydrase-3, myogenin, and fast-twitch fibre size were decreased. Importantly, in nonwasted COPD patients, where MyHC was more oxidised than in controls, its content was preserved. Muscle inflammation and glutathione levels did not differ between patients and controls. In all patients, muscle structure abnormalities were increased, while muscle force and exercise capacity were reduced.In severe COPD, while muscle oxidative stress increases regardless of their body composition, protein ubiquitination and loss of MyHC were enhanced only in patients exhibiting muscle atrophy. Oxidative stress does not seem to directly modulate muscle protein loss in these patients.
Exercise training reverses exertional oscillatory ventilation in heart failure patients
Authors: Zurek Marzena , Corrà Ugo , Piepoli Massimo F. , Binder Ronald K. , Saner Hugo , Schmid Jean-Paul 
Published: March 2012

Exertional oscillatory ventilation (EOV) is an ominous prognostic sign in chronic heart failure (CHF), but little is known about the success of specific therapeutic interventions.Our aim was to study the impact of an exercise training on exercise capacity and cardiopulmonary adaptation in stable CHF patients with left ventricular systolic dysfunction and EOV.96 stable CHF patients with EOV were included in a retrospective analysis (52 trainingversus44 controls). EOV was defined as follows: 1) three or more oscillatory fluctuations in minute ventilation (V′E) during exercise; 2) regular oscillations; and 3) minimal average ventilation amplitude ≥5 L.EOV disappeared in 37 (71.2%) out of 52 patients after training, but only in one (2.3%) out of 44 without training (p<0.001). The decrease of EOV amplitude correlated with changes in end-tidal carbon dioxide tension (r= -0.60, p<0.001) at the respiratory compensation point andV′E/carbon dioxide production (V′CO2) slope (r=0.50, p<0.001). Training significantly improved resting values of respiratory frequency (fR),V′E, tidal volume (VT) andV′E/V′CO2ratio. During exercise,V′EandVTreached significantly higher values at the peak, whilefRandV′E/V′CO2ratio were significantly lower at submaximal exercise. No change was noted in the control group.Exercise training leads to a significant decrease of EOV and improves ventilatory efficiency in patients with stable CHF.
Clinical analysis of 76 patients pathologically diagnosed with pulmonary cryptococcosis
Authors: Zhang Yuan , Li Nan , Zhang Yuxuan , Li Huiping , Chen Xueyuan , Wang Shanmei , Zhang Xia , Zhang Rongxuan , Xu Jinfu , Shi Jingyun , Yung Rex C. 
Published: March 2012

The aim of the present study was to investigate the clinical characteristics of pulmonary cryptococcosis patients in China, with analysis of immunocompetent and immunocompromised subjects.We performed a retrospective review of 76 patients diagnosed with tissue-confirmed pulmonary cryptococcosis at the Shanghai Pulmonary Hospital (Shanghai, China) during a 10-yr period (2001–2010).Of 76 patients (54 males and 22 females), 41 (53.95%) were immunocompetent and 35 out of the 41 were asymptomatic. Approximately 80% of the patients had histories suspicious of environmental fungal exposure. Radiological (computed tomography) findings showed predominantly peripheral findings (85.53%, 65 out of 76 patients) including nodular masses (55.26%, 42 out of 76), pneumonic infiltrates (23.68%, 18 out of 76) and mixed type (21.05%, 16 out of 76). 43.42% (33 out of 76) were initially misdiagnosed, often as cancer by false-positive18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) (28 out of 46 cases). 51 patients received antifungal therapy, 25 patients were clinically observed without treatment. As of December 31, 2010, 71 cases showed total recovery and four cases showed improvement (efficacy rate of 98.68%, 75 out of 76). One HIV-positive case died of cryptococcal meningitis.Incidence of pulmonary cryptococcosis in China may be related to environmental fungal exposures. Most presented as asymptomatic peripheral lung lesions. False-positive18FDG-PET examinations often lead to initial clinical misdiagnosis of cancer. Unlike immunocompromised or clinically symptomatic patients, all immunocompetent patients had a good response, either to fluconazole monotherapy or observation, with a tendency for spontaneous remissions in the asymptomatic immunocompetent subjects.
Severity assessment of healthcare-associated pneumonia and pneumonia in immunosuppression
Authors: Carrabba Maria , Zarantonello Marina , Bonara Paola , Hu Cinzia , Minonzio Francesca , Cortinovis Ivan , Milani Silvano , Fabio Giovanna 
Published: March 2012

The study compares the ability of the PSI (pneumonia severity index), CURB-65 (confusion, urea >7 mol·L−1, respiratory rate ≥30 breaths·min−1, blood pressure <90 mmHg systolic or ≤60 mmHg diastolic, and age ≥65 yrs), CURB and CRB-65 scales and the Severe Community-Acquired Pneumonia (SCAP) score to predict 30-day mortality in healthcare-associated pneumonia (HCAP) patients, and analyses differences in the demographics, aetiology and outcomes of community-acquired pneumonia (CAP), HCAP and pneumonia in immunocompromised patients.629 consecutive patients admitted to a tertiary care university hospital were prospectively categorised as having CAP (n=322) or HCAP (n=307), and the HCAP patients were further sub-divided into those who were immunocompromised (n=219) or immunocompetent (n=88).The 30-day mortality rate was 9.0% in the CAP group and 24.1% in the HCAP group. In the HCAP group, the PSI and SCAP scores had similar prognostic power (area under the curve (AUC) of 0.68 and 0.67, respectively) and performed better than the CURB-65 score (AUC ≤0.62). Among the immunocompetent HCAP patients, the PSI and CURB-65 scores were more sensitive than the others at every threshold, whereas SCAP was more specific than both of these. In the immunocompromised group, the PSI was highly sensitive but poorly specific at all thresholds.Our results suggest that prognostic tools should be designed for subsets of HCAP patients.
High-intensity knee extensor training restores skeletal muscle function in COPD patients
Authors: Brønstad Eivind , Rognmo Øivind , Tjonna Arnt Erik , Dedichen Hans Henrich , Kirkeby-Garstad Idar , Håberg Asta K. , Bjørk Ingul Charlotte , Wisløff Ulrik , Steinshamn Sigurd 
Published: March 2012

Improving reduced skeletal muscle function is important for optimising exercise tolerance and quality of life in chronic obstructive pulmonary disease (COPD) patients. By applying high-intensity training to a small muscle group, we hypothesised a normalisation of muscle function.Seven patients with COPD performed 6 weeks (3 days·week−1) of high-intensity interval aerobic knee extensor exercise training. Five age-matched healthy individuals served as a reference group. Muscle oxygen uptake and mitochondrial respiration of the vastus lateralis muscle were measured before and after the 6-week training programme.Initial peak work and maximal mitochondrial respiration were reduced in COPD patients and improved significantly after the training programme. Peak power and maximal mitochondrial respiration in vastus lateralis muscle increased to the level of the control subjects and were mainly mediatedviaimproved complex I respiration. Furthermore, when normalised to citrate synthase activity, no difference in maximal respiration was found either after the intervention or compared to controls, suggesting normal functioning mitochondrial complexes.The present study shows that high-intensity training of a restricted muscle group is highly effective in restoring skeletal muscle function in COPD patients.
The mechanism of deep inspiration-induced bronchoprotection: evidence from a mouse model
Authors: Wong Russell S. , Larcombe Alexander N. , Fernandes Lynette B. , Zosky Graeme R. , Noble Peter B. 
Published: March 2012

In healthy individuals, deep inspirations (DIs) taken prior to a bronchial challenge reduce the bronchoconstrictor response, which is termed “bronchoprotection”. The mechanism(s) of DI-induced bronchoprotection is unclear.The forced oscillation technique was used to assess the effect of prior DI on subsequent bronchoconstriction to methacholine (MCh) in BALB/c mice. We assessed likely mechanisms for the bronchoprotective effects of DI including reduced airway narrowing (from changes in airway resistance) and/or closure (changes in tissue elastance) and enhanced bronchodilation to a subsequent DI (% reversal in airway narrowing).DI prior to MCh challenge: 1) did not reduce but instead enhanced airway narrowing (p<0.05); 2) increased ventilation heterogeneity (p<0.05); 3) enhanced the subsequent bronchodilatory response to DI (p<0.05); and 4) reduced tissue elastance (p<0.05), suggesting opening of closed airways or alveoli units.Our findings suggest that DI prior to MCh challenge may elicit a series of changes, some of which are beneficial to respiratory function (enhanced bronchodilation), while others place greater load on the system (enhanced bronchoconstriction and ventilation heterogeneity). It is proposed that the relative magnitudes of these opposing physiological and mechanical effects will determine the net effect on respiratory function in health and disease.
Macrolide effects on the prevention of COPD exacerbations
Authors: Yamaya Mutsuo , Azuma Arata , Takizawa Hajime , Kadota Jun-ichi , Tamaoki Jun , Kudoh Shoji 
Published: March 2012

The number of senile patients with chronic obstructive pulmonary disease (COPD) has recently increased due to an increase in life expectancy, the habit of smoking and the inhalation of toxic particles. COPD exacerbations are caused by airway bacterial and viral infections, as well as the inhalation of oxidative substrates. COPD exacerbations are associated with the worsening of symptoms and quality of life, as well as an increased mortality rate.Several drugs, including long-acting anti-cholinergic agents, long-acting β2-agonists and inhaled corticosteroids, have been developed to improve symptoms in COPD patients and to prevent COPD exacerbations. Treatment with macrolide antibiotics has been reported to prevent COPD exacerbations and improve patient quality of life and symptoms, especially in those patients who have frequent exacerbations. In addition to their antimicrobial effects, macrolides have a variety of physiological functions, such as anti-inflammatory and anti-viral effects, reduced sputum production, the inhibition of biofilm formation and the inhibition of bacterial virulence factor production. These unique activities may relate to the prevention of exacerbations in COPD patients who receive macrolides.Herein, we review the inhibitory effects that macrolides have on COPD exacerbations and explore the possible mechanisms of these effects.
Interobserver variability in the application of the novel IASLC/ATS/ERS classification for pulmonary adenocarcinomas
Authors: Warth Arne , Stenzinger Albrecht , von Brünneck Ann-Christin , Goeppert Benjamin , Cortis Judith , Petersen Iver , Hoffmann Hans , Schnabel Philipp A. , Weichert Wilko 
Published: March 2012

Recently, a novel classification for pulmonary adenocarcinomas (ADCs) was published, the cornerstone of which is the quantification of growth patterns. Data on reproducibility in the routine diagnostic setting are lacking.100 constitutive cases of lung ADC resection specimens from our archives were classified independently by five pulmonary pathologists and two residents according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification.The most frequent predominant pattern in our cohort was solid (37%), followed by acinar (35%), lepidic (20%), papillary (5%) and micropapillary (3%). κ-values for the denomination of the predominant pattern revealed substantial agreement for pulmonary pathologists (κ=0.44–0.72) and fair agreement for residents (κ=0.38–0.47). Interobserver variability was significantly higher in cases with higher slide numbers (p=0.028) and was considerably reduced after training. Intraobserver variability was low (κ=0.79–0.87). Papillary and micropapillary patterns were the most complicated patterns to evaluate, while evaluation of lepidic and solid tumour growth was straightforward.Our data imply that the novel classification of pulmonary ADC is applicable with acceptable interobserver variability if performed by specifically trained pathologists. Additional efforts are needed to harmonise the application of this novel and clinically important classification scheme of pulmonary ADC.
Airway impedance entropy and exacerbations in severe asthma
Authors: Gonem Sherif , Umar Imraan , Burke Daniel , Desai Dhananjay , Corkill Steven , Owers-Bradley John , Brightling Christopher E. , Siddiqui Salman 
Published: March 2012

Variability of peak flow measurements has been related to clinical outcomes in asthma. We hypothesised that the entropy, or information content, of airway impedance over short time scales may predict asthma exacerbation frequency.66 patients with severe asthma and 30 healthy control subjects underwent impulse oscillometry at baseline and following bronchodilator administration. On each occasion, airway impedance parameters were measured at 0.2-s intervals for 150 s, yielding a time series that was then subjected to sample entropy (SampEn) analysis.Airway impedance and SampEn of impedance were increased in asthmatic patients compared with healthy controls. In a logistic regression model, SampEn of the resistance at 5 Hz minus the resistance at 20 Hz, a marker of the fluctuation of the heterogeneity of airway constriction over time, was the variable most strongly associated with the frequent exacerbation phenotype (OR 3.23 for every 0.1 increase in SampEn).Increased airway impedance and SampEn of impedance are associated with the frequent exacerbation phenotype. Prospective studies are required to assess their predictive value.