tbuckley/cabot-search huggingface dataset:
Abstract 2046: Hypercapnic Resuscitation Improves Survival and Neurological Outcomes by Nitric Oxide Synthase-Mediated Enhancement of Brain Perfusion
Authors: Wei-Tien Chang, Lay-San Gan, Chiang-Ting Chien, Chien-Hua Huang, Huei-Wen Chen, Kuo-Liong Chien, Chiung-Yuan Hsu, Min-Shan Tsai, Hsiao-Ju Cheng, Shyr-Chyr Chen, Yuan-Teh Lee, Wen-Jone Chen
Journal: Circulation (2008)

Neurological injury is one of the major causes of morbidity and mortality following cardiac arrest and cardiopulmonary resuscitation (CPR). Brain perfusion is usually compromised in the post-resuscitation phase, which inevitably lengthens the ischemic insult of the brain. Hypercapnia has been reported to cause cerebral vasodilatation. We therefore sought to study the potentials of hypercapnic resuscitation in improving the brain perfusion as well as survival and neurological prognoses. Using an established rat model of asphyxial cardiac arrest (6 min) and CPR, we employed hypercapnic (5% CO 2 , 95% O 2 ) ventilation during CPR and the first 2 h post-resuscitation, and compared the brain perfusion with normocapnia (5% N 2 , 95% O 2 ) control. The blood pressure was continuously monitored, with arterial blood sampled regularly for gas analysis. The tissue perfusion of the brain was measured by OxyLyte 2000E perfusion sensor. In a subgroup the survival and neurological outcomes were monitored up to 3 days. TdT-mediated dUTP nick-ends labeling (TUNEL) stain and Bax/Bcl2 of the brain were assessed as indicators of apoptotic cell death. The PaCO 2 was significantly higher ( P &lt;0.001) and pH significantly lower ( P &lt;0.001) in hypercapnia group during the first 2 h post-resuscitation. No difference was noted in PaO 2 or blood pressure. In normocapnia control, the brain perfusion was significantly reduced in the first 30 min post-resuscitation. Hypercapnic ventilation enhanced brain perfusion during this period ( P &lt;0.05). The survival and neurological outcomes were also improved (LogRank P &lt;0.05), which was consistent with the decrease in TUNEL stain and Bax/Bcl2. If nitric oxide (NO) synthase inhibitor N ω -nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) was cotreated with hypercapnia, the increased brain perfusion and reduced TUNEL and Bax/Bcl2 were reversed. The improved survival and neurological outcomes were also abrogated. Hypercapnic ventilation during CPR and early post-resuscitation phase improves brain perfusion and hence survival and neurological outcomes. This is in part mediated by NO synthase-related vasodilatation.
DNA methylation directs functional maturation of pancreatic β cells
Authors: Sangeeta Dhawan, Shuen-Ing Tschen, Chun Zeng, Tingxia Guo, Matthias Hebrok, Aleksey Matveyenko, Anil Bhushan
Journal: Journal of Clinical Investigation (2015)

Pancreatic β cells secrete insulin in response to postprandial increases in glucose levels to prevent hyperglycemia and inhibit insulin secretion under fasting conditions to protect against hypoglycemia. β cells lack this functional capability at birth and acquire glucose-stimulated insulin secretion (GSIS) during neonatal life. Here, we have shown that during postnatal life, the de novo DNA methyltransferase DNMT3A initiates a metabolic program by repressing key genes, thereby enabling the coupling of insulin secretion to glucose levels. In a murine model, β cell-specific deletion of Dnmt3a prevented the metabolic switch, resulting in loss of GSIS. DNMT3A bound to the promoters of the genes encoding hexokinase 1 (HK1) and lactate dehydrogenase A (LDHA) - both of which regulate the metabolic switch - and knockdown of these two key DNMT3A targets restored the GSIS response in islets from animals with β cell-specific Dnmt3a deletion. Furthermore, DNA methylation-mediated repression of glucose-secretion decoupling genes to modulate GSIS was conserved in human β cells. Together, our results reveal a role for DNA methylation to direct the acquisition of pancreatic β cell function.
Does exercising COPD patients on non invasive ventilation (NIV) enable them to walk further? A randomised controlled trial
Authors: Kathryn Buchan, Kathryn Badlan, Margaret Fletcher, Adrian Kendrick
Journal: European Respiratory Journal (2014)

Background:  The exercise component of pulmonary rehabilitation (PR) can improve activity in patients with severe COPD. However, these patients are repeatedly hospitalised, deconditioned and cannot access PR. NIV may offload the respiratory muscles relieving breathlessness allowing patients to train, which may increase fitness enabling patients to walk further.  Aim:  To identify potential differences in 6 minute walk test (6MWT) between patients with severe COPD who exercise on NIV and those receiving standard care.  Method:  18 patients with COPD (11 female, mean age 66.5 years [46-97], FEV1: mean 25% predicted [9-51%], MRC mean score 3 [1-4]) recruited following an admission for an exacerbation of COPD requiring treatment with NIV were randomised to 3 groups. Group 1 received standard hospital physiotherapy care, Group 2 exercised on NIV (Trilogy 100, Philips-Respironics) with a PS of 10 (10-16) twice weekly for the duration of the admission and Group 3 exercised on NIV during hospital stay and also twice weekly for 3 months following discharge. Exercise in all 3 groups included weights and pedal cycling or walking. All were followed up monthly for 3 months and 6MWT was measured.  Results:  Group 1: At baseline 6MWT was mean 49m (0-306m) and at end of study 6MWT was 40m (0-216m). Group 2: At baseline was 17m (0-38m) and at month 3 6MWT was 26m (5-70m). Group 3: At baseline 6MWT was 71m (0-315m) and at month 3 6MWT was 218m (84-494m). 15/18 final measures completed to date and 3/18 died during the study period.  Conclusions: There is a trend that the patients in group 3 had improved 6MWT compared to those in group 1 who demonstrated a decline in their 6MWT.
Dopamine and Norepinephrine in Noradrenergic Axons: A Study in Vivo of Their Precursor Product Relationship by Mass Fragmentography and Radiochemistry
Authors: E. Costa, A.R. Green, S.H. Koslow, H.F. LeFevre, A.V. Revuelta, C. Wang
Journal: Pharmacological Reviews (1972)

The results reported have shown that mass fiagmentography allows measurement of the DM pool in noradrenergic axons. By combining mass fragmentography and radiochemistry, it is possible to measure turnover rate of NE in heart ventricles from the precursor product relationship of DM and NE stored in the noradrenergic nerves. The turnover rate value obtained is compatible with those obtained by other approaches. Since the DM pool is the obligatory precursor for the NE, these data fail to give support to the view that there are several pools of NE in noradrenergic nerves which can be distinguished by virtue of their kinetic parameters.

A compartmentation can be distinguished concerning tyrosine in rat heart ventricles. From the relationship between tyrosine and DM we have calculated the size of the kinetic pool of tyrosine which serves as a precursor for DM and found that it is 12% of the total tyrosine in rat heart ventricles. Moreover, the specific radioactivity of this pool could be calculated to be 18-fold that of the rest of the tyrosine pool. These calculations of the tyrosine compartmentation rest on a number of assumptions which include the postulate that the DOPA pool is very small and that the transformation from DOPA to DM is practially instantaneous. The conversion by a soluble ensyme of DOPA into DM occurring in the cytoplasm supports this possibility.

The formation of DM, from a tyrosine pool, kept in a compartment which we have defined only kinetically yields a k 1''' (model b ) of 2.8 hr-1 indicating that 0.78 nanomoles/g/hr of DM turnover in 1 hr. By measuring the precursor product relationship between NE and DM we have obtained a turnover of NE of 0.69 nanomoles/g/hr. It is concluded that this value represents a reliable approximation of the absolute rate of NE synthesis in heart ventricles of rats
Characterisation of macrolide-non-susceptible Streptococcus pneumoniae colonising children attending day-care centres in Athens, Greece during 2000 and 2003
Authors: M. Souli, K. Volonakis, A. Kapaskelis, I. Galani, V. Grammelis, R. Vorou, M. Tsivra, Z. Chryssouli, D. Katsala, H. Giamarellou
Journal: Clinical Microbiology and Infection (2006)
LEPR K109R gene polymorphism and its association with OSA in North Indian subjects
Authors: Abhishek Dubey, Surya Kant, Sunita Tiwari, Sarita Aggarwal, Abbas Mahdi
Journal: European Respiratory Journal (2014)

Background:  Obesity is an established risk factor for Obstructive Sleep Apnea (OSA).Numerous studies had been reported association of LEPR K109R gene Polymorphism with obesity and related phenotype. Leptin, an adipocyte derived hormone, controls energy homeostasis and body weight.   Purpose:  The Aim of this study was to study the effect of Leptin Receptor (LEPR) gene polymorphism K109R at exon 4 on OSA phenotype in overweight and obese North Indian subjects.   Methods:  LEPR K109R Genotyping and Leptin level estimations were done in 285 subjects. All subjects went through overnight Polysomnography study, Anthropometrical (Body Mass index (BMI), Neck Circumference (NC), Waist Circumference (WC), Hip Circumference (HC) and Waist Hip Ratio (WHR)) and biochemical investigations (Leptin level, Lipid profile and Fasting Plasma Glucose level). Biochemical investigations were done with fasting blood samples of Subjects. Genomic DNA was isolated from blood of subjects with column based commercial kit. Genetic analysis was performed at LEPR 109 position by PCR-RFLP method using  Hae  III.   Results:  No association was observed in genotype distribution of subjects according to Occurrence and disease severity in LEPR K109R gene polymorphism. BMI, NC, WC, HC and WHR were not associated with LEPR K109R gene polymorphism. Fasting Lipid profile, Leptin levels and Plasma Glucose levels were also not associated with LEPR K109R gene polymorphism.   Conclusions:  These findings suggest that LEPR K109R gene Polymorphism is not associated with OSA occurrence, severity, metabolic and biochemical phenotype in overweight and obese Indian population.
Structural brain changes related to disease duration in patients with asthma
Authors: Andreas von Leupoldt, Stefanie Brassen, Hans Jörg Baumann, Hans Klose, Christian Büchel
Journal: European Respiratory Journal (2011)

Dyspnea is the impairing, cardinal symptom patients with asthma repeatedly experience over the course of the disease. However, its accurate perception is also crucial for timely initiation of treatment. Reduced perception of dyspnea is associated with negative treatment outcome, but the underlying brain mechanisms of perceived dyspnea in patients with asthma remain poorly understood. We examined, whether increasing disease duration of asthma is related to structural brain changes and studied the associations between structural brain changes and perceived dyspnea.  By using magnetic resonance imaging in combination with voxel-based morphometry, gray matter volumes of the insular cortex and brainstem periaqueductal grey (PAG) were examined in fourteen patients with mild-to-moderate asthma and correlated with asthma duration and perceived affective unpleasantness of resistive load induced dyspnea.  Whereas no associations were observed for the insular cortex, longer duration of asthma was associated with increased gray matter volume in the PAG. Moreover, increased PAG gray matter volume was related to reduced ratings of dyspnea unpleasantness.  The present results demonstrate that increasing disease duration is associated with increased PAG gray matter volume in patients with mild-to-moderate asthma. This structural brain change might contribute to reduced perception of dyspnea in some patients with asthma and, thus, negatively impact treatment outcome.
Attention deficit hyperactivity disorder in children
Authors: D. Bramble, A. Klassen, P. Raina, A. Miller, S. Lee, M S Thambirajah, A. Weaver, G. D Kewley
Journal: BMJ (1998)

Protecting children from armed conflictChildren affected by war must not be stigmatised as permanently damagedEditor-Southall and Abbasi quote Unicef when they state that the psychological consequences of armed conflict on children are so great that they can rarely be repaired. 1Unicef indeed says that "time does not heal trauma," but there is no sound empirical basis for a generalisation that risks stigmatising whole populations of children affected by war as sick or permanently damaged.Even child survivors of Auschwitz did not turn out like this as a general rule, and there are no published studies of children from non-Western war zones to support such a conlusion.Unicef and other agencies need to review such claims and costly interventions based on them; the claims owe more to prevailing sociocultural assumptions in the West than anything else.Over the past 50 years psychological explanations for life events and the medicalisation of distress have grown hugely.Because many people believe, for example, that rape or other criminal violence, childhood abuse, or even persistent bullying at school is an experience that may have lifelong psychological effects it seems unthinkable that war and atrocity should not do this to almost everyone exposed to them.Constructions of "trauma" deployed in the health field are increasingly expansive and undiscriminating. 2 No one wants to play down what children may suffer, or that war may produce clear psychological dysfunction in some (a minority).But it is not to their mental worlds but to their social worlds that survivors direct their attention, and humanitarian agencies should follow suit.The literature of both anthropology and mental health (in the case of mental health, starting with a classic study by Freud and Burlingham 3 ) shows the positive impact of family and community in buffering the short and longer term effects of war.The concept of child trauma is currently fashionable.But it is the social, cultural, and economic rebuilding of worlds shattered by war (including valued institutions such as schools), allied to urgent issues of equity and justice, which will determine the future wellbeing of several million child survivors worldwide. 4For those for whom this does not happen war may indeed mean a life sentence, but this is not trauma.
STAT3 Blockade Inhibits Radiation-Induced Malignant Progression in Glioma
Authors: Jasmine Lau, Shirin Ilkhanizadeh, Susan Wang, Yekaterina A. Miroshnikova, Nicolas A. Salvatierra, Robyn A. Wong, Christin Schmidt, Valerie M. Weaver, William A. Weiss, Anders I. Persson
Journal: Cancer Research (2015)

Abstract High grade gliomas (HGG) are classified into four subgroups based on transcriptional signatures and phenotypic characteristics. In particular, the proneural-to-mesenchymal transition (PMT) is associated with increased malignancy, poor prognosis, and disease recurrence, but the underlying causes of PMT are still unclear. In this study, we investigated whether radiotherapy promotes PMT using a genetically engineered mouse model of proneural HGG. We found that cranial ionizing radiation induced robust and durable PMT in tumors. Additionally, we isolated primary proneural HGG cells from mouse and human tumors and demonstrate that radiation induced a sustained cell-intrinsic mesenchymal transition associated with increased invasiveness and resistance to the alkylating agent temozolomide. Expectedly, irradiation-induced PMT was also associated with activation of the STAT3 transcription factor, and the combination of STAT3 blockade using JAK2 inhibitors with radiation abrogated the mesenchymal transition and extended survival of mice. Taken together, our data suggest that clinical JAK2 inhibitors should be tested in conjunction with radiation in patients with proneural HGG as a new strategy for blocking the emergence of therapy-resistant mesenchymal tumors at relapse. Cancer Res; 75(20); 4302–11. ©2015 AACR.
Superiority of ProMACE-CytaBOM over ProMACE-MOPP in the treatment of advanced diffuse aggressive lymphoma: results of a prospective randomized trial.
Authors: D L Longo, V T DeVita, P L Duffey, M N Wesley, D C Ihde, S M Hubbard, M Gilliom, E S Jaffe, J Cossman, R I Fisher
Journal: Journal of Clinical Oncology (1991)

One hundred ninety-three patients with stage II, III, or IV follicular large-cell, diffuse large-cell, diffuse mixed, immunoblastic, or diffuse small noncleaved-cell (non-Burkitt's) lymphoma were randomized to receive either cyclophosphamide 650 mg/m2 intravenously (IV), doxorubicin 25 mg/m2 IV, etoposide 120 mg/m2 IV on day 1, mechlorethamine 6 mg/m2 IV, vincristine 1.4 mg/m2 (no cap at 2 mg total dose) IV on day 8, prednisone 60 mg/m2 orally daily days 1 through 14, procarbazine 100 mg/m2 orally daily days 8 through 14, and methotrexate 500 mg/m2 IV on day 15 with leucovorin 50 mg/m2 orally every 6 hours for four doses beginning 24 hours after methotrexate with cycles repeated every 28 days (ProMACE-MOPP) or same day-1 treatment as ProMACE-MOPP plus cytarabine 300 mg/m2 IV, bleomycin 5 U/m2 IV, vincristine 1.4 mg/m2 (no cap at 2 mg total dose) IV, and methotrexate 120 mg/m2 IV on day 8, leucovorin 25 mg/m2 orally every 6 hours for four doses beginning 24 hours after methotrexate, and prednisone 60 mg/m2 orally daily days 1 through 14 with cycles repeated every 21 days (ProMACE-CytaBOM). Co-trimoxazole two double-strength tablets orally twice daily throughout the period of treatment was added to the ProMACE-CytaBOM regimen when an increased risk of Pneumocystis carinii pneumonia was found in the first 35 patients receiving this combination. Median follow-up is 5 years. Among the 99 patients treated with ProMACE-MOPP, 73 achieved a complete remission (CR) (74%), 30 complete responders have relapsed (41%), and 45 patients have died (45%), including two (2%) of treatment-related causes. Among the 94 patients treated with ProMACE-CytaBOM, 81 achieved a CR (86%), 22 complete responders have relapsed (27%), and 31 patients have died (33%). The complete response rate (P2 = .048) and survival (P2 = .046) were significantly higher for patients treated with ProMACE-CytaBOM. The mortality of ProMACE-CytaBOM treatment overall was six of 94 patients (6.4%). There was no treatment-related mortality among patients treated with prophylactic co-trimoxazole (n = 59). ProMACE-CytaBOM combination chemotherapy with co-trimoxazole prophylaxis is a safe and effective treatment for patients with aggressive histology malignant lymphoma and is superior to ProMACE-MOPP.
Characterization of inflammation in bronchoalveolar lavage of lung transplant patients
Authors: Cristina Berastegui, Sara Sánchez-Vidaurre, Mario Culebras, Víctor Monforte, Manuel López-Meseguer, Carlos Bravo, Iker López, Ricardo Zapata, María Jesús Cruz, Antonio Román
Journal: European Respiratory Journal (2013)

Introduction : Inflammation plays an important role in the lung allograft’s long-term viability. The definition of the inflammatory profile based on the patient9s condition is not well established. The aim of this study was to characterize the patterns of lung inflammation in patients who underwent lung transplantation (LT).   Material and methods : Sixty LTs were performed in 25 women and 35 men between July 2010 and January 2012 (age: 45 years, range 22-67). Nine LTs were unipulmonary and 51 were bipulmonary. LT patients were divided into three groups: 1, stable (n=18), 2, pulmonary infection (n=18) and 3, chronic allograft dysfunction (CAD) (n=24). At the time of the study the mean postoperative follow-up was 37.3 (11.6-115) months. Bronchoalveolar lavage (BAL) samples were analyzed to determine differential cell count and to measure inflammatory biomarkers: Interleukin (IL)-4, IL-5, IL-6, TNFα, IFNγ, IL-10, IL-13, IL -17, GM-CSF, and total bile acids (TBA).   Results : We observed higher percentage of BAL neutrophils in group 3 compared to groups 1 and 2 (p= 0.006, p=0.014 respectively). Increased levels of IL-17 and IL-13 were observed in group 2 compared to group 3 (p=0.046, p=0.034, respectively). We found higher concentrations of IL-10, GM-CSF and TBA in group 3 compared to group 1 (p= 0.05, p=0.010 and p=0.010, respectively).   Conclusions : A distinct inflammatory profile was observed among patients with CAD and those with an acute allograft infection. The increased levels of TBA in CAD group supports the hypothesis that gastroesophageal reflux plays a role in its pathophysiology.
Aminophylline enhances ventilation in phrenicotomized rats
Authors: J Nachazel, F Palecek
Journal: European Respiratory Journal (1990)

The aim was to test the effects of aminophylline (AP) on breathing of phrenicotomized rats. Fifty seven male rats of the Wistar strain were anaesthetized with 1.3 g.kg-1 urethane i.p. They were phrenicotomized, divided into 6 groups and given 5, 10, 20, 40 and 80 mg.kg-1 AP i.v. or a corresponding volume of saline. Ventilation, tracheal occlusion pressure and arterial blood gases were measured. In all animals phrenicotomy resulted in hypoventilation with corresponding hypoxaemia (from control 11.9 +/- 1.0 to 10.4 +/- 0.8 kPa) and hypercapnia (from control 4.6 +/- 0.5 to 5.5 +/- 0.6 kPa). In the control group (with saline) 4 h later the PaO2 was 8.6 +/- 1.1 kPa and PaCO2 7.2 +/- 0.6 kPa. After AP 1 h after phrenicotomy the minute ventilation increased in a dose-dependent manner by 1-66%. 4 h after phrenicotomy the minute ventilation of rats with 20 and 40 mg.kg-1 of AP was significantly higher than that of the control group. AP prevented hypoventilation when injected into phrenicotomized rats. The results give no unequivocal basis from which to decide the proportion of central and peripheral effects of AP.
Analysis of Clinical Factors For Ambulatory Management In Patients With Febrile Neutropenia
Authors: I. Matos, R. Lozano Mejorada, C.A. Rodríguez, S. Alfonso, R.A. Marcos, R. Vidal, C. Guillén, A. Noguerido, O. Rúa, E. Del Barco, L.M. Navarro, J.J. Cruz Hernandez
Journal: Annals of Oncology (2014)
NOS1-derived nitric oxide promotes NF-κB transcriptional activity through inhibition of suppressor of cytokine signaling-1
Authors: Mirza Saqib Baig, Sofia V. Zaichick, Mao Mao, Andre L. de Abreu, Farnaz R. Bakhshi, Peter C. Hart, Uzma Saqib, Jing Deng, Saurabh Chatterjee, Michelle L. Block, Stephen M. Vogel, Asrar B. Malik, Marcia E.L. Consolaro, John W. Christman, Richard D. Minshall, Benjamin N. Gantner, Marcelo G. Bonini
Journal: The Journal of Experimental Medicine (2015)

The NF-κB pathway is central to the regulation of inflammation. Here, we demonstrate that the low-output nitric oxide (NO) synthase 1 (NOS1 or nNOS) plays a critical role in the inflammatory response by promoting the activity of NF-κB. Specifically, NOS1-derived NO production in macrophages leads to proteolysis of suppressor of cytokine signaling 1 (SOCS1), alleviating its repression of NF-κB transcriptional activity. As a result, NOS1−/− mice demonstrate reduced cytokine production, lung injury, and mortality when subjected to two different models of sepsis. Isolated NOS1−/− macrophages demonstrate similar defects in proinflammatory transcription on challenge with Gram-negative bacterial LPS. Consistently, we found that activated NOS1−/− macrophages contain increased SOCS1 protein and decreased levels of p65 protein compared with wild-type cells. NOS1-dependent S-nitrosation of SOCS1 impairs its binding to p65 and targets SOCS1 for proteolysis. Treatment of NOS1−/− cells with exogenous NO rescues both SOCS1 degradation and stabilization of p65 protein. Point mutation analysis demonstrated that both Cys147 and Cys179 on SOCS1 are required for its NO-dependent degradation. These findings demonstrate a fundamental role for NOS1-derived NO in regulating TLR4-mediated inflammatory gene transcription, as well as the intensity and duration of the resulting host immune response.