tbuckley/cabot-search huggingface dataset:
Late-breaking abstract: Maternal genetic asthma predisposition affects pulmonary microRNA profiles in neonatal offspring
Authors: Stefan Dehmel, Agnieszka Pastula, Rabea Imker, Nikola Schulz, Oliver Eickelberg, Adalbert Roscher, Susanne Krauss-Etschmann
Journal: European Respiratory Journal (2011)

Introduction:  Exposure-induced deregulation of microRNAs (miRs) during early critical developmental periods has been proposed to contribute to the propagation of asthma risk in later life.   Aim:  We asked if maternal genetic asthma predisposition is sufficient to affect pulmonary miR profiles in offspring that do not bear the genetic asthma risk. To address this question, we used female mice with a heterozygous deficiency for Tbx21 as they develop spontaneous airway remodeling and airway hyperreactivity (Finotto et al., Science, 2002; 295:336).   Methods:  Female C57BL/6J Tbx21+/- mice were mated with WT males. Neonatal lungs from male WT offspring of dams with (Tbx21+/-, n=5) and without genetic asthma predisposition (WT, n=3) were removed within 24h after birth and total mRNA including small RNAs was extracted. Duplicate pools of RNAs were subjected to miR expression profiling (ABI, TaqMan® Array microRNA cards).  In silico  target prediction was performed for miRs with a >1.5x change followed by pathway analysis (DIANA-mirpath, TargetScan).   Results:  Male WT offspring of Tbx21+/- dams showed an up-regulation of 14 of 750 miRs (1.5-2.1x), while 17 miRs were down-regulated (1.5-4.7x) compared to male WT offspring of dams without genetic asthma predisposition. Pathway analysis showed a significant enrichment of target genes within the WNT pathway (49 of 154 genes). MiRs 27a* and 124 were found to target multiple genes (≥15) in the WNT pathway suggesting a key regulatory function for these miRs in WNT signaling.   Conclusion:  These data show that maternal genetic asthma predisposition affects pulmonary miR profiles during an early developmental stage and might therefore influence lung development.
Evaluation of bone marrow and blood cultures for the recovery of mycobacteria in the diagnosis of disseminated mycobacterial infections
Authors: E. Pacios, L. Alcalé, M.J. Ruiz-Serrano, D.G. de Viedma, M. Rodríguez-Créixems, M. Marín-Arriaza, J Berenguer, E Bouza
Journal: Clinical Microbiology and Infection (2004)
Increasing prevalence of asthma diagnosis and symptoms in children is confined to mild symptoms
Authors: G. Ng Man Kwong, A. Proctor, C. Billings, R. Duggan, C. Das, M.K.B. Whyte, C.V.E. Powell, R.A. Primhak
Journal: Thorax (2001)

<h3>BACKGROUND</h3> The prevalence of childhood asthma is increasing but few studies have investigated trends in asthma severity. We investigated trends in asthma diagnosis and symptom morbidity between an eight year time period in a paired prevalence study. <h3>METHODS</h3> All children in one single school year aged 8–9 years in the city of Sheffield were given a parent respondent questionnaire in 1991 and 1999 based on questions from the International Survey of Asthma and Allergy in Children (ISAAC). Data were obtained regarding the prevalence of asthma and wheeze and current (12 month) prevalences of wheeze attacks, speech limiting wheeze, nocturnal cough and wheeze, and exertional symptoms. <h3>RESULTS</h3> The response rates in 1991 and 1999 were 4580/5321 (85.3%) and 5011/6021 (83.2%), respectively. There were significant increases between the two surveys in the prevalence of asthma ever (19.9%<i>v</i> 29.7%, mean difference 11.9%, 95% confidence interval (CI) 10.16 to 13.57, p&lt;0.001), current asthma (10.3% <i>v</i> 13.0%, mean difference 2.7%, 95% CI 1.44 to 4.03, p&lt;0.001), wheeze ever (30.3%<i>v</i> 35.8%, mean difference 5.7%, 95% CI 3.76 to 7.56, p&lt;0.001), wheeze in the previous 12 months (17.0%<i>v</i> 19.4%, mean difference 2.5, 95% CI 0.95 to 4.07, p&lt;0.01), and reporting of medication use (16.9%<i>v</i> 20%, mean difference 3.0%, 95% CI 1.46 to 4.62, p&lt;0.001). There were also significant increases in reported hayfever and eczema diagnoses. <h3>CONCLUSIONS</h3> Diagnostic labelling of asthma and lifetime prevalence of wheeze has increased. The current 12 month point prevalence of wheeze has increased but this is confined to occasional symptoms. The increased medication rate may be responsible for the static prevalence of severe asthma symptoms. The significant proportion of children receiving medication but reporting no asthma symptoms identified from our 1999 survey suggests that some children are being inappropriately treated or overtreated.
Inhibition of collagen receptors: α1β1 and α2β1 integrins, has no impact on lymphocytes, but decreases eosinophil transmigration through human extracellular matrix and collagen I coated inserts
Authors: Stanislawa Bazan-Socha, Joanna Zuk, Cezary Marcinkiewicz, Jacek Musial
Journal: European Respiratory Journal (2011)

Introduction:  T helper lymphocytes are likely to play a pivotal role in directing disease development and progression in asthma. We recently described presence of α1 and α2 integrins on blood eosinophils and α2 on blood CD4 and CD8 T lymphocytes in chronic asthma. We hypothesize that collagen receptors: α1β1 and α2β1 integrins may play an important role in cell transmigration to the sites of asthmatic inflammation.   Methods:  We studied effects of functional active, mouse anti-human monoclonal antibodies against I-domain of α1 and α2 integrin subunit (Chemicon, USA) on eosinophil and lymphocyte transmigration through human extracellular matrix and collagen I coated cell culture inserts (Beckton Dickinson Falcon Cell Culture Inserts – 3 μm pore size). In 6 atopic asthmatics lymphocytes were separated from peripheral blood by gradient centrifugation and eosinophils by gradient centrifugation and negative magnetic separation (Vario MACS, Miltenyi Biotec).   Results:  None of the antibodies used influenced lymphocyte transmigration through human extracellular matrix and collagen I coated inserts. However, movement of peripheral blood eosinophils through human extracellular matrix was inhibited by both antibodies (% of inhibition: 30±26 for anti-α1, 25±24 for anti-α2 mAb). Anti-α2 mAb was also active on collagen I coated inserts (37 ± SD33); anti-α1 mAb was not effective.   Conclusion:  The α2β1 integrin is present on lymphocytes, but seems to play no role in lymphocyte infiltration. However, both α1β1 and α2β1 integrins might be important in eosinophil transmigration and support airway inflammation.
Activity of moxifloxacin against the urogenital mycoplasmas Ureaplasma spp., Mycoplasma hominis and Mycoplasma genitalium and Chlamydia trachomatis
Authors: C.M. Bébéar, B. de Barbeyrac, S. Pereyre, H. Renaudin, M. Clerc, C. Bébéar
Journal: Clinical Microbiology and Infection (2008)
Evaluation of factors affecting mortality rate in sarcoidosis
Authors: Elias Gialafos, Vasileios Kouranos, Anastasios Kallianos, Tsoukas David, Theodore Papaioannou, Sotiria Stampola, Elias Peros, Ioannis Arapis, Charalambos Kostopoulos, Georgia Mpirmpa, John Gialafos, Aggeliki Rapti
Journal: European Respiratory Journal (2011)

Introduction:  Five to 10% are the mortality rates reported in patients with sarcoidosis worldwide. However, little are known about the factors affecting the survival.   Methods:  We conducted an observational study to examine factors affecting survival in patients with sarcoidosis. Totally 122 patients with biopsy-proven sarcoidosis enrolled, underwent pulmonary function tests, a 12-lead electrocardiogram, an echocardiogram and a 24-hour Holter monitoring. Cardiac sarcoidosis was detected based on known criteria. All-cause mortality and cardiac death were the primary and secondary endpoints.   Results:  During a median of 58.89±15.75 months follow-up, ten deaths (8.2%) were reported. The demographic characteristics of the survived patients and those who died are presented in table 1.  Five patients (4.1%) died due to cardiac causes. Cardiac involvement was detected in 40 patients (32.8%). The multivariate analysis showed age, standard deviation of RR intervals    Conclusion:  The thorough evaluation of the results from a full cardiopulmonary monitoring in patients with sarcoidosis may be able to detect factors related with increased risk of mortality.
Protein starvation and the small intestine
Authors: Jan S. Hirschfield, Fred Kern
Journal: Journal of Clinical Investigation (1969)

Weanling rats were fed diets which contained either no protein or 27% protein. In one experiment after 23-35 days both groups were given l-leucine-4,5-(3)H either intragastrically or intraperitoneally and then sacrificed 24 hr later. In a second experiment animals were given these diets for 21 days and sacrificed 3, 6, or 12 hr after either intragastric or intraperitoneal administration of the labeled leucine. In both experiments the intestinal mucosa of proximal and distal segments of the small intestine was scraped, weighed, the protein concentration measured, and the specific activty of the mucosal protein was determined. The wet weight of the mucosa and the protein concentration of the mucosa were significantly greater in the control animals than in the protein-depleted animals. The mucosal protein per 100 g of body weight was the same in the protein-deprived and the control groups. The specific activity of the intestinal mucosal protein was higer in the protein-deprived animals than in the control animals. In the protein-deprived animals the proximal segment incorporated more radioactive amino acid into mucosal protein than did the distal segment at 3, 6, 12, and 24 hr after the amino acid was given by mouth. A similar difference was found between the proximal and distal segments of the control animals 6 hr after oral adminisstration of l-leucine-(3)H. On the other hand, when the l-leucine-(3)H was given intraperitoneally to both groups of animals there was no difference between proximal and distal small intestine. These findings suggest that intestinal mucosal protein can be synthesized directly from intraluminal amino acids, especially during protein deprivation, and that endogenous intraluminal protein might be important in the nutrition of the small intestinal mucosa.
Bone Scan Appearances after Uncemented Hip Replacement
Authors: A B Ashbrooke, P T Calvert
Journal: Journal of the Royal Society of Medicine (1990)

Persistent increased uptake on a technetium bone scan after a cemented hip replacement usually indicates pathology, either loosening or infection. The natural history of scan appearances in uncemented replacements is different and can be predicted from a plain X-ray. The diagnostic value of a bone scan is therefore questionable when investigating pain after uncemented hip replacement.
The serious illness care program.
Authors: Rachelle Bernacki, Susan Block
Journal: Journal of Clinical Oncology (2014)

12 Background: Conversations between patients and clinicians about end-of-life care allow patients to prepare and plan for the end of life and are associated with improved outcomes. Objective: To determine the impact of a structured, seven-item conversation guide on anxiety and depression in patients with an estimated prognosis under a year. Methods: A cluster, randomized controlled trial enrolled 81 clinicians and 272 patients (goal of 400 patients) at Dana Farber Cancer Institute. The intervention (integrated into regular clinical care by oncologists) consisted of a system to identify patients and trigger clinician discussions using the checklist, clinician training, and documentation template in the electronic medical record. Adult patients were identified by oncologists using the “surprise” question. Surveys measured key outcomes before and after administration of the checklist (for patients) and after training (for oncologists). Results: 1,299 patients were identified using the surprise question. Of patients contacted, 332 agreed to participate and 254 declined. To date, 62 conversations are complete with a median length of 20 minutes (range: 8-70 min). The mean anxiety level using the GAD-7 score for the participants with complete data prior to the checklist conversation was 4.0 and post-conversation 3.1 (p=0.04). The mean depression score using the PHQ-9 prior to the checklist conversation was 6.3 and post-conversation 5.7 (p=0.2). 51% of patients found the discussion ‘very’ or ‘extremely’ helpful; 21% found the discussion ‘somewhat’ helpful; and 14% ‘slightly’ or ‘not at all’ helpful. The majority of clinicians found the guide simple (79%) and easy to use (78%); 81% reported they would continue its use after the trial. Conclusions: These preliminary data demonstrate that use of the guide is feasible, acceptable to patients and clinicians, and does not lead to increased anxiety or depression. There is a trend towards a significant reduction in anxiety in patients who had the discussion with their oncologists. The Serious Illness Care Program is an acceptable intervention to support clinicians in conducting conversations about end-of-life values and goals with patients, allowing them to articulate their wishes about future medical care. Clinical trial information: NCT01786811.
Effects of δ 9 -Tetrahydrocannabinol in Lewis Lung Adenocarcinoma Cells in Tissue Culture 2
Authors: A. C. White, J. A. Munson, A. E. Munson, R. A. Carchman
Journal: JNCI Journal of the National Cancer Institute (1976)

We found a dose-related decrease in DNA synthesis in transformed cell cultures treated with δ9-tetra-hydrocannabinol (δ9-THC). The decrease, observed over a 4-hour period, was not accompanied by a change in the radioactive precursor pool as compared to that of control cultures. The distribution of labeled products clearly differed from that observed after treatment with cytosine arabinoside. δ9-THC inhibited DNA synthesis at some point beyond the uptake of 3H-thymidine.
Molecular Biomarkers in Gastric Cancer
Authors: Elena Elimova, Roopma Wadhwa, Hironori Shiozaki, Kazuki Sudo, Jeannelyn S. Estrella, Brian D. Badgwell, Prajnan Das, Aurelio Matamoros, Shumei Song, Jaffer A. Ajani
Journal: Journal of the National Comprehensive Cancer Network (2015)

Gastric cancer (GC) represents a serious health problem on a global scale. Despite some recent advances in the field, the prognosis in metastatic GC remains poor. Even in localized disease the adjunctive therapies improve overall survival (OS) by only approximately 10%. A better understanding of molecular biology, which would lead to improved treatment options, is needed and is the basis for this review. Many potential biomarkers of prognostic significance have been identified, including ALDH, SHH, Sox9, HER2, EGFR, VEGF, Hippo/YAP, and MET. However, inhibition of only HER2 protein has led to a modest survival benefit. A new approach to GC treatment, which is a disease influenced by inflammation, is the exploitation of the immune system to fight disease. Two interesting targets/prognostic markers that bear further investigation in GC are PD1 and PDL, particularly given their success in the treatment of other inflammation/immune-associated malignancies.
Effect of the combination of doxofylline and montelukast on LPS-induced leukocyte migration to the lung
Authors: Yanira Vasquez, Clive Page
Journal: European Respiratory Journal (2014)

We have previously demonstrated that Doxofylline (Dox) at 1 and 0.3 mg/kg significantly inhibited leukocyte migration and cytokine release in a murine model of lung inflammation induced by lipopolysaccharide (LPS) (Riffo-Vasquez et. al., Pulm. Pharm. Ther. 2014, Epub.) Montelukast (Mltk) is a leukotriene receptor antagonist used in the treatment of allergic lung diseases, often alongside xanthines. In this study we have investigated the effect of the combination of Dox and Mltk in a model of lung inflammation induced by LPS.  Methods : Dox (0.3 mg/kg i.p.) and Mltk (0.3 mg/kg, oral or 1 mg/kg i.p.) were administrated -24, -1 and 6 h after LPS (10 µg/mice, i.n.) in Balb/c mice. The combination of the drugs did not induce any adverse effects. Lung lavage was performed 24 h later.  Results : LPS recruited significantly higher number of neutrophils (PMN) to the lung (mean±SEM x 10 6 /ml) compared to saline (saline:0±0  vs  LPS:1.8±0.15, n=6). Dox alone significantly inhibited the recruitment of PMN (LPS/Dox:1.02±0.1, n =5; p vs  LPS). Mltk alone by oral administration or i.p. had no significant effect on the number of PMN (LPS/Mtlk oral:1.99±0.19, LPS/Mtlk i.p.:1.64±0.31, n=5 and 4, respectively). The combination of Dox and Mltk did not provide any further significantly effect on the number of PMN recruited to the lung in response to LPS (LPS/Dox±Mtlk oral.:2.34±0.34, LPS/Dox±Mtlk i.p.:1.9±0.2, n=5 and 4, respectively).  Conclusion:  Doxofylline is an effective anti-inflammatory drug, a property not shared by montelukast in this model. Therefore, combination treatment of doxofylline and montelukast gives additional benefits compared to montelukast as mono therapy.
Genomic Landscape of <i>CXCR4</i> Mutations in Waldenström Macroglobulinemia
Authors: Stéphanie Poulain, Christophe Roumier, Aurélie Venet-Caillault, Martin Figeac, Charles Herbaux, Guillemette Marot, Emmanuelle Doye, Elisabeth Bertrand, Sandrine Geffroy, Frédéric Lepretre, Olivier Nibourel, Audrey Decambron, Eileen Mary Boyle, Aline Renneville, Sabine Tricot, Agnès Daudignon, Bruno Quesnel, Patrick Duthilleul, Claude Preudhomme, Xavier Leleu
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Whole-genome sequencing has revealed MYD88 L265P and CXCR4 mutations (CXCR4mut) as the most prevalent somatic mutations in Waldenström macroglobulinemia. CXCR4 mutation has proved to be of critical importance in Waldenström macroglobulinemia, in part due to its role as a mechanism of resistance to several agents. We have therefore sought to unravel the different aspects of CXCR4 mutations in Waldenström macroglobulinemia. Experimental Design: We have scanned the two coding exons of CXCR4 in Waldenström macroglobulinemia using deep next-generation sequencing and Sanger sequencing in 98 patients with Waldenström macroglobulinemia and correlated with SNP array landscape and mutational spectrum of eight candidate genes involved in TLR, RAS, and BCR pathway in an integrative study. Results: We found all mutations to be heterozygous, somatic, and located in the C-terminal domain of CXCR4 in 25% of the Waldenström macroglobulinemia. CXCR4 mutations led to a truncated receptor protein associated with a higher expression of CXCR4. CXCR4 mutations pertain to the same clone as to MYD88 L265P mutations but were mutually exclusive to CD79A/CD79B mutations (BCR pathway). We identified a genomic signature in CXCR4mut Waldenström macroglobulinemia traducing a more complex genome. CXCR4 mutations were also associated with gain of chromosome 4, gain of Xq, and deletion 6q. Conclusions: Our study panned out new CXCR4 mutations in Waldenström macroglobulinemia and identified a specific signature associated to CXCR4mut, characterized with complex genomic aberrations among MYD88L265P Waldenström macroglobulinemia. Our results suggest the existence of various genomic subgroups in Waldenström macroglobulinemia. Clin Cancer Res; 22(6); 1480–8. ©2015 AACR.
£40m is wasted on GP data extraction IT system that does not work properly
Authors: Ingrid Torjesen
Journal: BMJ (2015)

The £40m (€56m; $62m) General Practice Extraction Service (GPES), the IT system designed to allow NHS organisations to extract data from general practice computer systems in England for monitoring and research purposes, cannot provide the services intended, an investigation by the National Audit Office (NAO) has shown.1

The GPES was meant to extract data from general practice computer systems in England to allow NHS organisations to monitor quality, to plan and pay for health services, and to aid research. It was also intended to play a key role in the care.data initiative to enable the Health and Social Care Information Centre (HSCIC) to extract patient information from GPs’ computer systems and align it with Hospital Episode Statistics data extracted through the Secondary Uses Service system, to provide a comprehensive NHS dataset.

However, four years after GPES was scheduled to start, just one customer, NHS England, has received data through …
Down regulation of Wip1 phosphatase in MCF-7 breast cancer cells enhances doxorubicin-induced DNA damage and apoptosis
Authors: W. Mercer
Journal: Clinical Cancer Research (2008)

B48  MCF-7 breast cancer cells harbor an amplified PPM1D/Wip1 gene and over express Wip1 phosphatase. We show first that modulating Wip1 expression has both positive and negative affects on the growth of MCF-7 cells. Stable isogenic MCF-7 sublines designated as MCF-clones were established in which Wip1 protein expression was significantly down regulated by introduction of a plasmid-based PPM1D antisense RNA. Decreased Wip1 expression sensitized the MCF-clones to doxorubicin-mediated DNA damage-induced apoptosis. The enhanced apoptotic response was correlated with an increase in total p53 protein and N-terminal phosphoforms of p53-Ser15 and p53-Ser46. In addition increased expression of the pro-apoptotic Bax gene occurred at both the mRNA and protein level. Bax-siRNA knock down abrogated the enhanced apoptotic response mediated by increased Bax protein expression. Assays using the Waf1 and Bax promoters to drive a luciferase reporter gene revealed that luciferase activity driven by the Bax promoter was enhanced in MCF-clones while luciferase activity driven by the Waf1 promoter was decreased relative to parental MCF-7 cells. The study reveals a novel molecular mechanism involving Wip1 phosphatase knock-down, increased N-terminal p53 phosphorylation and an enhanced apoptotic response mediated by transcriptional activation of the Bax gene. Our results suggest that Wip1 phosphatase should be considered as a potential therapeutic target in breast tumors and other tumor types that over express it and provides a rationale for combining Wip1 knock-down strategies with anticancer drugs that induce DNA damage.
Community adquired legionella pneumophila pneumonia in elderly patients
Authors: Luis Alberto Ruiz, Sonia Castro, Ainhoa Gómez, Amaia Sagarna, Estibaliz Pérez, Elena Urra, Amaia Urrutia, Ruth Diez, Rafael Zalacain
Journal: European Respiratory Journal (2014)

AIM: To evaluate differences in clinical presentation and outcome in elderly patients admitted to our hospital with CAP due to  Legionella pneumophila.   METHODS: We have included patients with CAP due to  L. pneumophila  admitted to our hospital between 01-01-2002 and 31-12-2013. Patients were divided in two groups: 1- Age L. pneumophila  urinary antigen.  RESULTS: We evaluated 208 patients (60 elderly). Compared to younger, elderly patients were more likely to be female (p=0,048), current smokers (p=0,0001) and heavy drinkers (p=0,0001). Comorbid conditions diabetes mellitus (p=0,025), congestive heart disease (p=0,002), COPD (p=0,028) and clinical symptoms like altered mental status (p=0,001) were more common in elderly. Laboratory abnormalities such as hyponatremia (p=0,0001) were more frequent in younger but leukocytes(p=0,015) and BUN levels (p=0,0001) were higher in elderly, who also had higher PSI (p=0,0001), CURB65 (p=0,0001) but no differences in ICU admission and mechanical ventilation. There were no differences in hospital stay (9,8 vs 10,6 days) and mortality rates (11,6% vs 5,4%, p= 0,08) between elderly and young.  CONCLUSIONS: 1- Comorbidities and altered mental status were more common in elderly patients. 2-There were no differences in ICU admissions rate although elderly patients were in more severe clinical condition according to PSI and CURB. 3- Higher mortality in elderly patients but no significant differences.