tbuckley/cabot-search huggingface dataset:
Oxidative stress in children with OSAS: Role of urinary 8-isoprostane
Authors: Susanna Bonafoni, Susanna Fedeli, Valentina Negro, Maria Chiara Supino, Maria Chiara Paolino, Rosa Castaldo, Manuela Cecili, Maurizio Simmaco, Maria Pia Villa
Journal: European Respiratory Journal (2011)

Background:  In Obstructive Sleep Apnea Syndrome (OSAS), the key role of airway inflammation is confirmed. Studies about noninvasive methods and new markers of inflammation in diagnosis and management of pediatric OSAS are increasing. 8-IsoP is an oxidative stress marker.The study of this marker in urines of children with OSAS could be promising.   Aim:  To evaluate urinary 8-IsoP values in children with OSAS   Methods:  Twenty children (mean age 6.33±2.06, M/F:12/8), with referred OSAS, underwent urinary collection at the morning after the polysomnography, sleep questionnaire, medical examination. 8-IsoP was assessed in urinary sample.   Results:  According to the AHI (Apnoea/Hypopnea index) obtained from the polysomnography, we found 13 subjects (group1) with primary snoring/minimum OSAS (mean AHI 1.89±1.80; mean SaO2 97.59±0.59) and 7 subjects (group2) with moderate/severe OSAS (mean AHI 14.65±11.09; mean SaO2 96.04±2.98). The urinary 8-IsoP values is higher in Group 2 (respectively Group1:0,72±0,57 ng/ml  vs  Group2: 2.19±1.29 ng/ml, p=0.01). Moreover we found a positive correlation between AHI and urinary 8Iso-P (r= 0,5; p=0,02). The linear regression analysis, performed using as dependent variable values of urinary 8-Isop and as independent variables severity of OSAS, age, sex, AHI, SaO2, Prick test, BMI percentile, adenotonsillar ipertrophy, showed that the severity of OSAS was the only predictor for levels of urinary 8-Isop (R Square: 0.415).   Conclusion:  Our data show that values of urinary 8-IsoP are related to OSAS severity. Further studies are needed to assess the utility of urinary 8-Isop as marker of inflammation likely due to oxidative stress.
Allergy to rabbits
Authors: J. A. Price, J. L. PLongbottom
Journal: Allergy (1988)

Quantitative immunoelectrophoretic techniques have been used to study the antigenic components found in extracts of dust collected from rabbit housing areas. To determine the possible source of these antigens, comparisons have been made to rabbit saliva, urine, fur and dander. Specific antisera for the rabbit extracts were raised in guinea pigs. One major component of the dust (Ag R1) was also found in large amounts in saliva, slightly less in fur and in only minimal amounts in urine and dander. Crossed radioimmunoelectrophoresis (XRIE) of the dust, performed with sera from 14 rabbit allergic individuals who were RAST positive to rabbit saliva, urine and dust identified four IgE‐binding constituents. Individual responses varied but all sera reacted with Ag R1, identifying this as a major rabbit allergen. Dust RAST inhibition studies with rabbit dust, saliva and urine indicated saliva to be closely related to the dust. Ag R1 is a glycoprotein which appears to be very heterogeneous in nature. It produced a broad biphasic precipitin peak on immunoelectrophoresis and eluted from Sephacryl S‐200 gel filtration over the molecular weight range 30–50 Kd, although a molecular weight of 17 Kd was indicated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS‐PAGE) and gradient gel electrophoresis. The RAST inhibition results and the antigenic similarity of saliva to the dust suggest this to be the most likely source of the major rabbit allergen, Ag R1.
AAV-Tgfb1 vs. bleomycin: Analysis of gene expression profiles in two models of pulmonary fibrosis
Authors: Benjamin Strobel, Germán Leparc, Bärbel Lämmle, Tobias Hildebrandt, Birgit Stierstorfer, Thorsten Lamla, Sebastian Kreuz
Journal: European Respiratory Journal (2014)

Translating clinically relevant disease mechanisms into early preclinical research is key for the successful development of new pharmaceutical drugs. For pathway-focused studies, viral vector-mediated overexpression or knockdown prove very useful to modulate target gene function  in vivo . Particularly, Adenovirus (Ad) vectors have been used to set up respiratory disease models. However, even improved Ad vectors induce substantial inflammation following application into the lung, possibly interfering with disease-relevant pathways and therefore limiting their use.  To identify an efficient alternative vector with the lowest possible immunogenicity, we carried out a systematic comparison of a commonly used Ad5 vector and an Adeno-associated virus (AAV) 6-based vector. While the Ad5 vector induced an inflammatory response including T-cell activation, the AAV vector did not cause any measurable immune response. We then successfully applied this AAV vector to establish a pulmonary fibrosis model in mice by overexpression of  Tgfb1 . Characterization based on immune cell analysis, histology and lung function measurement confirmed fibrosis manifestation. For in-depth analysis of fibrosis development over time, we applied deep sequencing to profile changes in gene expression, particularly in comparison to the commonly used bleomycin model. The increased understanding of the molecular pathways involved will help to decide in the future, which of the models is appropriate to answer defined scientific questions in pulmonary fibrosis research and preclinical drug development.
The role of pathogen genomics in assessing disease transmission
Authors: V. Sintchenko, E. C. Holmes
Journal: BMJ (2015)

Whole genome sequencing (WGS) of pathogens enables the sources and patterns of transmission to be identified during specific disease outbreaks and promises to transform epidemiological research on communicable diseases. This review discusses new insights into disease spread and transmission that have come from the use of WGS, particularly when combined with genomic scale phylogenetic analyses. These include elucidation of the mechanisms of cross species transmission, the potential modes of pathogen transmission, and which people in the population contribute most to transmission. Particular attention is paid to the ability of WGS to resolve individual patient to patient transmission events. Importantly, WGS data seem to be sufficiently discriminatory to target cases linked to community or hospital contacts and hence prevent further spread, and to investigate genetically related cases without a clear epidemiological link. Approaches to combine evidence from epidemiological with genomic sequencing observations are summarised. Ongoing genomic surveillance can identify determinants of transmission, monitor pathogen evolution and adaptation, ensure the accurate and timely diagnosis of infections with epidemic potential, and refine strategies for their control.
Two simultaneous outbreaks of multidrug-resistant tuberculosis - Federated States of Micronesia, 2007-2009.
Authors: D. Fred, M. Ekiek, B. Pavlin, R. Brostrom, M. Haddad, S. Bamrah, A. Heetderks, M. Desai, R. Song
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
Abstract 3446: Fibroblast growth factor 23 promotes prostate cancer cell proliferation and invasiveness <i>in vitro</i>
Authors: Shu Feng, Michael Ittmann
Journal: Cancer Research (2014)

Abstract Prostate cancer is the most common malignancy among American men and remains the second leading cause of male cancer mortality. Since age is thought to be one of the crucial factors in prostate cancer development, fibroblast growth factor 23 (FGF23), which forms a complex with Klotho, the age-related gene product, could play a key role in prostate development and progression. FGF23 is a peptide hormone member of the endocrine FGF subfamily (FGF19, FGF21, and FGF23), which signals through FGF receptors (FGFRs) in the presence of the coreceptor α-Klotho. FGF-23 has a critical role in phosphate homeostasis and vitamin D metabolism. The regulation of 1,25-Dihydroxyvitamin D by FGF-23 could also have implications for cancers, given that vitamin D metabolites have been shown to have anticarcinogenic effects. It has been reported that higher concentrations of FGF-23 were found in patients with advanced ovarian cancer compared with those with early-stage cancer or control subjects; circulating FGF-23 is associated with an increased risk of colorectal adenoma; however, to date, no investigations of the role of FGF-23 in prostate cancer have been reported. In the present study we investigated the function of FGF23 on human prostate cancer progression. FGF23 gene expression was determined in the commonly used prostate cancer cell lines: PC3, LNCaP, DU145, VCaP, and an immortalized normal prostate cell line PNTIA. RT-PCR showed that both FGF23 and αKlotho (KLA) genes are expressed in all these cell lines. Quantitative real-time RT-PCR indicated that FGF23 gene expression is elevated in prostate cancer compared to normal prostate tissue; FGF23 expression frequency is significantly higher in prostate cancer in compare with normal tissue (prostate cancer: total case number 35, positive 23; normal prostate tissue: total number 33, positive 15; p=0.04841). Biological function assays demonstrated that exogenous FGF23 stimulates prostate cancer cell proliferation (LNCaP by 30%, PC3 20%), anchorage-independent growth (by 60% for both LNCaP and PC3 cells), and invasion (LNCaP by 50% and PC3 55%). Suppression of FGF23 expression by FGF23 short hairpin RNA (shRNA) significantly inhibits PC3 and LNCaP cell proliferation, soft agar colony formation, and invasiveness in vitro. These data suggest that FGF23 promotes human prostate cancer progression and targeting FGF23 signaling pathway could decrease prostate cancer growth and metastasis. Citation Format: Shu Feng, Michael Ittmann. Fibroblast growth factor 23 promotes prostate cancer cell proliferation and invasiveness in vitro. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3446. doi:10.1158/1538-7445.AM2014-3446
Epithelial mesenchymal transition (EMT) is present in both large and small airways of smokers
Authors: Malik Mahmood, Sukhwinder Singh Sohal, Ashutosh Hardikar, David Reid, Cameron Hunter, Darryl Knight, Konard Muller, Eugene Haydn Walters
Journal: European Respiratory Journal (2014)

Introduction :Airway remodelling is seen in COPD in both small and large airways. Small airway fibrosis is the main contributor in airflow obstruction in COPD; EMT has been implicated in this. In large airways we have shown active EMT to be associated with angiogenesis i.e, malignancy-associated Type-3 EMT.   Objective :In this study we have investigated whether EMT biomarkers are expressed in small airways compared to large airways, and what type of EMT is present on the basis on vascularity of airway epithelium and Reticular basement membrane (Rbm).   Methods :Cross-sectionally we evaluated Rbm fragmentation (core structural marker of EMT) and EMT-related mesenchymal bio-markers in small and large airways from resected lung tissue from 24 COPD lung cancer patients and, 9 normal controls using immunohistochemistry. Tissues were immunostained using antibodies against Vimentin (mesenchymal marker) and S100-A4 (fibroblast epitope).Type-IV collagen was stained to demonstrate vessels.   Results :There was significantly increased expression of EMT-related markers in small airways compared to control tissue: Vimentin(p l0.001), S100-A4(pl0.001) and fragmentation(pl0.001). However, levels of EMT expression were less than in large airways. Notably there was no hyper vascularity in small airway Rbm as there was in large airways (pl0.001 against large airways; p=1 against normal).   Conclusion :EMT is active in small airway in COPD suggesting a potential role in small airway fibrosis, i.e, EMT-Type 2; in contrast to Type-3 EMT in large airways where it could be important in promoting cancer formation.
Institutional Responses to Prospective Payment Based on Diagnosis-Related Groups
Authors: Robert S. Stern, Arnold M. Epstein
Journal: New England Journal of Medicine (1985)

OVER the next three years, cost-based reimbursement for hospital services rendered to Medicare recipients will be eliminated.1 Medicare's decision to adopt instead a prospective payment system based on diagnosis-related groups (DRGs) represents a potential revolution in the nation's health care delivery system. Under the new system, hospitals will be paid on a per case basis with fixed payment for each of 467 DRGs.Proponents of the DRG system believe that it will solve many of the ills now attributed to cost-based reimbursement. In his report to Congress, former Secretary of Health and Human Services Richard Schweiker suggested that a DRG-based . . .
Factors associated with Staphylococcus aureus nasal carriage among healthy people in Northern China
Authors: X. Yan, Y. Song, X. Yu, X. Tao, J. Yan, F. Luo, H. Zhang, J. Zhang, Q. Li, L. He, S. Li, F. Meng, J. Zhang, H. Grundmann
Journal: Clinical Microbiology and Infection (2014)

There is still limited knowledge about the prevalence and risk factors of nasal carriage for Staphylococcus aureus among healthy carriers in China. We investigated 2448 healthy adults (≥18 years of age) from Beijing (n = 1530) and Harbin (n = 918) by nasal screening. Participants were checked for carriage of S. aureus, and health-related and demographic information between 2009 and 2011 was gathered. A total of 403 S. aureus (403/2448, 16.5%) were recovered, 8 of which were methicillin resistant (8/2448, 0.33%). Three factors were independently associated with S. aureus nasal carriage: Harbin as city of residence (odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.41 to 2.85), age ≤24 years (OR = 1.77, 95% CI = 1.30–2.44) and non-Han ethnicity (OR = 1.58, 95% CI = 1.05 to 2.38). On the basis of population genetic analysis using multiple locus variable number of tandem repeats analysis (MLVA) and spa typing, MLVA complex (MC) 398 and MC5a were the most prevalent clonal lineages in this collection. In multivariate models, residing in Harbin (OR = 1.77, 95% CI = 1.07–2.92) and having household members in the healthcare profession (OR = 3.69, 95% CI = 1.14–11.92) were factors associated with carriage of clonal lineage MC398. On the other hand, female sex (OR = 3.15, 95% CI = 1.35–7.33) and a history of chronic liver disease (OR = 16.93, 95% CI = 2.91–98.59) were associated with the clonal lineage MC5a. The three most common spa types were t571 (10.9%), t189 (9.9%) and t701 (7.2%). These findings provide insight into the determinants of nasal carriage and ecology for some of the most successful strains of S. aureus among healthy people in Northern China.
Pneumocystis Pneumonia—Los Angeles
Authors: Gottlieb Ms, Schanker Hm, Fan Pt, Saxon A, Weisman Jd, Pozalski I
Journal: JAMA (1996)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Positron Emission Tomography Using [<sup>18</sup>F]Fluorodeoxyglucose for Monitoring Primary Chemotherapy in Breast Cancer
Authors: M. Schelling, N. Avril, J. Nährig, W. Kuhn, W. Römer, D. Sattler, M. Werner, J. Dose, F. Jänicke, H. Graeff, M. Schwaiger
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To address the role of positron emission tomography (PET) using [ 18 F]fluorodeoxyglucose (FDG) to monitor primary (neoadjuvant) chemotherapy in patients with locally advanced breast cancer. PATIENTS AND METHODS: Quantification of regional FDG uptake of the breast acquired after the first and second courses of chemotherapy was compared with the baseline scan in 22 patients with a total of 24 breast carcinomas. To evaluate the predictive value of PET imaging, histopathologic response after completion of chemotherapy classified as gross residual disease (GRD) or minimal residual disease (MRD) served as the gold standard. RESULTS: Significant differences in tracer uptake between nonresponding tumors (GRD) and responding lesions (MRD) were observed (P &lt; .05) as early as after the first course of chemotherapy. Tracer uptake showed little change in tumors with GRD found later in pathologic analysis but decreased sharply to the background level in most tumors with MRD. After the first course, all responders were correctly identified (sensitivity 100%, specificity 85%) by a standardized uptake value decrease below 55% of the baseline scan. At this threshold, histopathologic response could be predicted with an accuracy of 88% and 91% after the first and second courses of therapy, respectively. CONCLUSION: This study demonstrates that in patients with advanced breast cancer undergoing primary chemotherapy, FDG-PET differentiates responders from nonresponders early in the course of therapy. This may help improve patient management by avoiding ineffective chemotherapy and supporting the decision to continue dose-intensive preoperative chemotherapy in responding patients.
Collection of year-round hay fever symptoms using a public website (www.allergieradar.nl)
Authors: Letty A. de Weger, Eefje B. Op den Buysch, Arnold J.H. van Vliet
Journal: European Respiratory Journal (2011)

Introduction:  On average 10-20% of the population in the industrialized world suffers from pollen allergy, also known as hay fever. The geographical distribution and severity of hay fever symptoms in the Netherlands year-round is largely unknown.   Aims and objectives:  Our objective was to study whether symptoms collected by an interactive internet platform from participants characterized by an internet questionnaire can provide relevant information on hay fever.   Methods:  On May 13 2009 the website www.allergieradar.nl was launched. Participants could register by completing an extensive questionnaire on their hay fever (symptoms, doctor diagnosis, etc). Once registered, participants regularly entered their geographical position and their symptoms of nose, eyes and lungs on a scale from 1-10. All data from 2009 (May 13-Dec 31) and 2010 (Jan 1-Dec 31) were stored in a database and analysed.   Results:  Approx. 7000 entries with symptoms scores were collected in 2009 and in 2010 by 884 and 491 participants, respectively. More than 80% of the participants reported a doctor diagnosed hay fever. The majority of these participants suffered from nose and eye symptoms (>92%) and approx. 50% (also) from lung symptoms. The daily mean maximum symptom score of these participants correlated with the logarithm of the daily pollen counts (correlation coefficient=0.549, p   Conclusions:  We conclude that these internet symptom scores are a valuable tool in studies on hay fever symptoms in the general population and for the development of hay fever forecasts.
Phase I trial with a combination of docetaxel and <sup>153</sup>Sm- EDTMP in patients (pts) with castration-resistant metastatic prostate cancer (mCRPC)
Authors: M. A. Eisenberger, J. Lin, V. J. Sinibaldi, M. A. Carducci, S. Denmeade, T. DeWeese, D. Song
Journal: Journal of Clinical Oncology (2009)

5155 Background: Bone targeted therapy holds great promise for improving outcomes in mCRPC. Preclinical data strongly supported biological synergism of docetaxel (Tax) and 153 Sm-EDTMP (Sm) in mCRPC. Concurrent Tax and Sm regimens were reported feasible and tolerable in phase I studies. This study was designed to evaluate toxicity and preliminary efficacy of 2 cycles (12 wks/cycle, C) of concomitant standard dose/schedule of Sm plus Q3 wks schedule of Tax in mCRPC. Methods: mCRPC pts with progressive bone metastases were treated in 4 cohorts ( CH). Previous Tax and palliative RT to bone was admissible. Dose escalation of Tax was implemented if no DLT was observed in the preceding CH. Tax doses (on days 1, 22, per 12 wk cycle) were given as follows: CH 1- 50mg/m 2 (C1 and 2); CH 2–75mg/m 2 (C1) and 50mg/m 2 (C2); CH3 - 75mg/m 2 (C1 and 2) and CH4 ( Tax day 1, 22, 43 per 12 wk C) 75mg/m 2 (C1 and 2). Sm was administered on days 2 (Q12 wks X 2) at dose of 1 mCi/kg/cycle (max. of 2 cycles). Disease status was assessed (with bone /CT scans and PSA) after every cycle. Results: Thirteen pts with progressive bone metastases were enrolled. Three had prior Tax and 3 had prior palliative radiation. Thirteen pts received total 20 cycles in 4 cohorts. Toxicity was primarily hematological. There were total 34 episodes Grade 3/4 neutropenia with a median 7 (range 7 -14) days to recovery to ≤ grade1. Tax dose was reduced to 50% in 2 CH4 pts at C2. Only 1 DLT G3 thrombocytopenia occurred on cohort 4 with duration of 9 wks. Median baseline PSA was 100.4 ng/ml (range 8.6 - 1064), 9/13 (69%) pts had PSA&gt;50% decrease. Median time to disease progression was 147 days (range 72 days - 10 months + ); 6/13 (46%) pts had stable/improved bone scans at 6 months and 8/8 (100%) symptomatic pts had improvement in pain. Conclusions: Concurrent 6-month administration of 2 and possibly 3 full dose /standard schedule of Tax with 2 full doses of Sm is feasible with reversible bone marrow suppression. The combination may provide additional clinical benefits for mCRPC pts with extensive bone metastasis. No significant financial relationships to disclose.
A novel inhaled PI3Kδ inhibitor, LAS194223 reduces allergen-induced airway inflammation in rat
Authors: Marta Calbet, Martin Lehner, Elena Calama, Anna Domenech, Judit Cabedo, Maria Dominguez, Montse Erra, Jorge de Alba, Neus Prats, Montserrat Miralpeix
Journal: European Respiratory Journal (2014)

Rationale: PI3Kd is a lipid kinase involved in the activation, proliferation and differentiation of leukocytes and thus is an anti-inflammatory target for the treatment of asthma and COPD.  Aim: To describe the in vivo efficacy of a new PI3Kd inhibitor, LAS194223 in a model of ovalbumin (OVA)-induced airway inflammation in Brown Norway rat by inhaled route compared to fluticasone.  Methods: The pharmacokinetic profile of LAS194223 was assessed by intratracheal administration in male Wistar rats using a Liquid MicroSprayer. Plasma and lung concentrations were measured at time points ranging from 0.01 to 24 h. LAS194223 was administered by i.t. route to OVA-sensitized Brown Norway rats 1 h prior to the OVA challenge and BAL as well as lung tissue for histological evaluation were obtained 24 h post challenge. Total and differential BAL cell counting were performed by Sysmex. Cytokine levels were measured using Luminex technology. PenH was measured by whole body plethysmography.  Results: In the OVA model intratracheal administration of LAS194223 inhibited OVA induced late asthmatic response (LAR), measuring PenH, by 79% at 1 mg/kg, dose-dependently inhibited the eosinophil, neutrophil counts and cytokine levels in BAL. In the lung tissue, it inhibited the alveolar inflammation, alveolar hemorrhages and interstitial edema.  Conclusions: The inhaled administration of the LAS194223 inhibits OVA induced changes in lung function and inflammation. Therefore, LAS194223 shows a promising profile for further characterization and suggests that PI3Kd inhibition, by inhaled route could be a potential treatment for asthma and COPD.