tbuckley/cabot-search huggingface dataset:
Airway inflammation in waste handlers exposed to bioaerosols assessed by induced sputum
Authors: K.K. Heldal, A.S. Halstensen, J. Thorn, W. Eduard, T.S. Halstensen
Journal: European Respiratory Journal (2003)

Work-associated lower airway inflammation in waste collectors was examined by induced sputum and correlated with the bioaerosol exposure. Organic waste collectors (n=25) underwent induced sputum collection and spirometry before work on Monday and the following Thursday. Total cells, cell differentials, interleukin (IL)-8 and eosinophilic cationic protein were determined. Personal full-shift exposure measurements were performed Monday, Tuesday and Wednesday and analysed for total bacteria, fungal spores, endotoxins and beta(1-3)-glucans. The percentage of neutrophils (46-58%) and the IL-8 concentration (1.1-1.4 ng x mL(-1)) increased from Monday to Thursday. Forced expiratory volume in one second (FEV1) was significantly reduced on Thursday, and the decrease in FEV1/forced vital capacity correlated with the increase in the percentage of neutrophils. The median exposure to endotoxin (range 7-180 EU x m(-3)) and beta(1-3)-glucan (range 5-220 ng x m(-3)) was correlated with the increase in IL-8. Bioaerosol exposure during waste collection induced an inflammatory response in the lower airways, characterised by neutrophils and interleukin-8 secretion, that influenced the lung function. The inflammatory response was related to microbial components in the bioaerosol and was more pronounced for endotoxin than beta(1-3)-glucan exposure. No associations were found for mould spores or bacteria.
A bcl-2 transgene expressed in hepatocytes protects mice from fulminant liver destruction but not from rapid death induced by anti-Fas antibody injection.
Authors: I Rodriguez, K Matsuura, K Khatib, J C Reed, S Nagata, P Vassalli
Journal: The Journal of Experimental Medicine (1996)

Stimulation of the Fas (APO-1, CD95) receptor, which is present on a variety of cells, usually triggers a process of programmed cell death. Systemic injection of anti-Fas antibody into mice leads to fulminant liver destruction resulting from massive hepatocyte apoptosis, and to rapid death. Hepatocytes bear Fas but do not express Bcl-2, a protein that plays, in a number of conditions, a protective role against apoptosis. We have generated mice whose liver expresses Bcl-2 as the result of bcl-2 transgene placed under the control of the hepatocyte-specific alpha1-anti-trypsin gene promoter, but is otherwise not distinguishable from that of normal mice. These mice display a marked to almost total resistance to liver damage induced by anti-Fas antibody injection. This protective effect of Bcl-2 occurs in the absence of significant variations, in the stimulated livers, in the level of expression of other proteins also involved in resistance or sensitivity to apoptosis, namely Bcl-x, Bax, Bad, Bak, and p53. Mice with protected livers, however, die almost as rapidly as normal mice, which indicates that acute lethality results from stimulation of Fas receptors present on other target organs or cells.
Measurement of Left Ventricular Volume by Biplane Angiocardiography and Indicator-Washout Techniques: A Comparison in the Canine Heart
Authors: STUART H. BARTLE, MIGUEL E. SANMARCO
Journal: Circulation Research (1966)

Left ventricular volumes were determined sequentially in 31 dogs and simultaneously in 12 by biplane angiocardiography and a dye-dilution, thermal washout technique. The mean ejected fraction (SV/EDV; systolic volume/end diastolic volume) was significantly higher when measured by angiocardiography (.53 ± .03) than by the washout method (.27 ± .02). The end diastolic volume measured by angiocardiography was lower, 21.1 ± 1.5 ml/10 kg versus 34.4 ± 3.6, as was the end systolic volume, 11.3 ± 1.3 ml/10 kg versus 25.5 ± 3.2. Mean stroke volume by angiocardiography was 10.9 ml/10 kg, or 1.8 ml greater than by dye dilution (the average amount of contrast material injected per beat was 1.9 ml/10 kg). No difference was found between the washout fractions calculated from early and from late beats. There was a significant inverse correlation between the observed heart rate and washout SV/EDV. There was no correlation between heart rates and the discrepancy in measuring the various volumes. Technical difficulties and theoretical considerations are discussed and it is concluded that in dogs the angiographic method gives more accurate calculations of end diastolic and end systolic volumes than the washout technique. The latter method appears to underestimate SV/EDV systematically, probably because of incomplete mixing of indicator in the ventricle. This leads to falsely high values for EDV and ESV.
Atypical Antipsychotic Administration During Late Pregnancy: Placental Passage and Obstetrical Outcomes
Authors: D. Jeffrey Newport, Martha R. Calamaras, C. Lindsay DeVane, Jennifer Donovan, Aquila J. Beach, Stephanie Winn, Bettina T. Knight, Bryan B. Gibson, Adele C. Viguera, Michael J. Owens, Charles B. Nemeroff, Zachary N. Stowe
Journal: American Journal of Psychiatry (2007)

Objectives: There are limited data regarding the use of atypical antipsychotic medications in pregnancy. The objectives of the current study were to quantify placental permeability to antipsychotic medications and to document obstetrical outcomes for women taking these agents proximate to delivery. Method: The authors conducted a prospective observational study of women treated with an atypical antipsychotic or haloperidol during pregnancy. Maternal and umbilical cord plasma samples collected at delivery were analyzed for medication concentrations. Placental passage was defined as the ratio of umbilical cord to maternal plasma concentrations (ng/ml). Obstetrical outcome was ascertained through maternal reports and reviews of obstetrical records. Results: Fifty-four pregnant women with laboratory-confirmed antipsychotic use proximate to delivery were included in the analysis. Complete maternal-infant sample pairs were available for 50 participants. Placental passage ratio was highest for olanzapine (mean=72.1%, SD=42.0%), followed by haloperidol (mean=65.5%, SD=40.3%), risperidone (mean=49.2%, SD=33.9%), and quetiapine (mean=23.8%, SD=11.0%). There were tendencies toward higher rates of low birth weight (30.8%) and neonatal intensive care unit admission (30.8%) among neonates exposed to olanzapine. Conclusions: All four antipsychotics demonstrated incomplete placental passage. Quetiapine demonstrated the lowest placental passage of the medications studied. These novel data provide an initial quantification of the placental passage of antipsychotics and fetal exposure in humans, demonstrating significant differences between individual medications.
CD146 is a coreceptor for VEGFR-2 in tumor angiogenesis
Authors: Tianxia Jiang, Jie Zhuang, Hongxia Duan, Yongting Luo, Qiqun Zeng, Kelong Fan, Huiwen Yan, Di Lu, Zhongde Ye, Junfeng Hao, Jing Feng, Dongling Yang, Xiyun Yan
Journal: Blood (2012)
Quality of life and disease-related symptoms in previously treated Japanese patients with non-small-cell lung cancer: results of a randomized phase III study (V-15-32) of gefitinib versus docetaxel
Authors: I Sekine, Y Ichinose, Y Nishiwaki, N Yamamoto, M Tsuboi, K Nakagawa, T Shinkai, S Negoro, F Imamura, K Eguchi, K Takeda, Y Itoh, T Tamura, N Saijo, M Fukuoka
Journal: Annals of Oncology (2009)
Lung Cancer Screening
Authors: Douglas E. Wood, George A. Eapen, David S. Ettinger, Lifang Hou, David Jackman, Ella Kazerooni, Donald Klippenstein, Rudy P. Lackner, Lorriana Leard, Ann N. C. Leung, Pierre P. Massion, Bryan F. Meyers, Reginald F. Munden, Gregory A. Otterson, Kimberly Peairs, Sudhakar Pipavath, Christie Pratt-Pozo, Chakravarthy Reddy, Mary E. Reid, Arnold J. Rotter, Matthew B. Schabath, Lecia V. Sequist, Betty C. Tong, William D. Travis, Michael Unger, Stephen C. Yang
Journal: Journal of the National Comprehensive Cancer Network (2012)

2][3][4] In 2011, it is estimated that 156,900 deaths (85,600 in men, 71,300 in women) from lung cancer will occur in the United States. 4Five-year survival rates for lung cancer are only approximately 15.6%, partly because most patients have advanced-stage lung cancer at initial diagnosis (http:// seer.cancer.gov/statfacts/html/lungb.html). 5hese facts, combined with the success of screening in improving outcomes in cervical, colon, and breast cancers,
Mammalian Target of Rapamycin Pathway Blockade Slows Progression of Diabetic Kidney Disease in Rats
Authors: Núria Lloberas, Josep M. Cruzado, Marcella Franquesa, Immaculada Herrero-Fresneda, Joan Torras, Gabriela Alperovich, Inés Rama, August Vidal, Josep M. Grinyó
Journal: Journal of the American Society of Nephrology (2006)

Recent data suggest that the phosphatidylinositol 3-kinase (PI3-K)/Akt/mammalian target of rapamycin (mTOR) pathway is important in diabetic nephropathy. The effect of mTOR blockade by sirolimus (SRL) in diabetic kidney disease in rats was investigated. Diabetes was induced by streptozotocin in male Sprague-Dawley rats. Sixteen weeks later, diabetic animals were divided into the following groups: diabetes (D; <i>n</i> = 8), diabetes + SRL at 1 mg/kg per d, SRL trough level 2.3 ± 0.25 ng/ml (D+SRL; <i>n</i> = 7); and diabetes + normoglycemia maintained by insulin implants (D+NG; <i>n</i> = 5). There was an age-matched nondiabetic group (ND; <i>n</i> = 6). All animals were followed for 4 wk. The D group showed glomerular hypertrophy (mean glomerular volume 5.0 ± 0.4 in D <i>versus</i> 3.3 ± 0.2 10<sup>6</sup> μ<sup>3</sup> in ND; <i>P</i> &lt; 0.05) without renal hyperplasia (calculated by reverse transcription-PCR of proliferative cell nuclear antigen) and albuminuria (29 ± 4 in D <i>versus</i> 1.4 ± 1.5 mg/24 h in ND; <i>P</i> &lt; 0.05). Both D+NG and D+SRL groups had a significant reduction of albuminuria, although glomerular hypertrophy was still present. SRL treatment did not modify the number of infiltrating renal ED1<sup>+</sup> cells. Diabetic animals had greater expression of p-Akt and mTOR, unlike ND rats. NG and SRL treatment reduced p-Akt and normalized mTOR. It is interesting that D+SRL was associated with a significant reduction of renal TGF-β1 and glomerular connective tissue growth factor. SRL treatment reduced glomerular α-smooth muscle actin overexpression and reduced significantly the mesangial matrix accumulation that is characteristic of diabetic nephropathy. In conclusion, mTOR blockade by low-dose SRL has a beneficial effect in diabetic kidney disease, suggesting that the mTOR pathway has an important pathogenic role in diabetic nephropathy.
Circulating Retinol-Binding Protein-4, Insulin Sensitivity, Insulin Secretion, and Insulin Disposition Index in Obese and Nonobese Subjects
Authors: Norbert Stefan, Anita M. Hennige, Harald Staiger, Erwin Schleicher, Andreas Fritsche, Hans-Ulrich Häring
Journal: Diabetes Care (2007)

In the recent article by Broch et al. (1), circulating retinol-binding protein-4 (RBP4) (measured by nephelometry) was not correlated with adiposity or insulin sensitivity; however, negative correlations with indexes of insulin secretion were detected. The authors concluded that RBP4 may impair β-cell function in human subjects.

This is an interesting hypothesis, particularly because retinol seems to be required for adequate glucose-stimulated insulin secretion (2). However, retinoids in blood are not exclusively transported by RBP4 but also by albumin and lipoprotein particles (3). This suggests that the availability of retinoids in …
Predictive role of smoking in the development of mucociliary insufficiency in patients with chronic non-obstructive bronchitis
Authors: Victor P. Kolosov, Andrey N. Odireev, Artem V. Kolosov
Journal: European Respiratory Journal (2011)

Background:  Smoking in patients with chronic bronchitis can lead to decrease of effectiveness of mucociliary clearance (MCC) and to development of mucociliary insufficiency at the early stages of a disease formation.   Aim:  To study the peculiarities of mucociliary system functioning in patients with chronic non-obstructive bronchitis (CNOB) depending on smoking factor.   Methods:  Spirography, the study of MCC by scintigraphy with  99m Tc, the measurement of frequency of bronchial epithelium cilia beating in bronchial biopsy material in vitro were carried out in 79 patients with CNOB. There were 45 smokers (1st group) and 34 non-smokers (2nd group) at the age from 25 till 30 years old, the duration of the disease was no more than 5 years.   Results:  There was no statistically significant difference between the groups of smokers and non-smokers in FEV 1  (92,4±3,5 and 96,8±2,6%, respectively). The integral index of MCC in the 1st group were lower than in the 2nd group (36,2±2,9 and 40,5±3,3% an hour, respectively, p 2 =9,31; p   Conclusion:  The decrease of MCC is typical for smokers with CNOB with latent lung function disturbance. It is suggested the early correction of MCC failure is essential for optimization of CNOB clinical course.
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of Oral Sildenafil Citrate in Treatment-Naive Children With Pulmonary Arterial Hypertension
Authors: Robyn J. Barst, D. Dunbar Ivy, Guillermo Gaitan, Andras Szatmari, Andrzej Rudzinski, Alberto E. Garcia, B.K.S. Sastry, Tomas Pulido, Gary R. Layton, Marjana Serdarevic-Pehar, David L. Wessel
Journal: Circulation (2011)

Safe, effective therapy is needed for pediatric pulmonary arterial hypertension.Children (n=235; weight ≥8 kg) were randomized to low-, medium-, or high-dose sildenafil or placebo orally 3 times daily for 16 weeks in the Sildenafil in Treatment-Naive Children, Aged 1-17 Years, With Pulmonary Arterial Hypertension (STARTS-1) study. The primary comparison was percent change from baseline in peak oxygen consumption (PV(O(2))) for the 3 sildenafil doses combined versus placebo. Exercise testing was performed in 115 children able to exercise reliably; the study was powered for this population. Secondary end points (assessed in all patients) included hemodynamics and functional class. The estimated mean±SE percent change in PV(O(2)) for the 3 doses combined versus placebo was 7.7±4.0% (95% confidence interval, -0.2% to 15.6%; P=0.056). PV(O(2)), functional class, and hemodynamics improved with medium and high doses versus placebo; low-dose sildenafil was ineffective. Most adverse events were mild to moderate in severity. STARTS-1 completers could enter the STARTS-2 extension study; patients who received sildenafil in STARTS-1 continued the same dose, whereas placebo-treated patients were randomized to low-, medium-, or high-dose sildenafil. In STARTS-2 (ongoing), increased mortality was observed with higher doses.Sixteen-week sildenafil monotherapy is well tolerated in pediatric pulmonary arterial hypertension. Percent change in PV(O(2)) for the 3 sildenafil doses combined was only marginally significant; however, PV(O(2)), functional class, and hemodynamic improvements with medium and high doses suggest efficacy with these doses. Combined with STARTS-2 data, the overall profile favors the medium dose. Further investigation is warranted to determine optimal dosing based on age and weight.http://www.clinicaltrials.gov. Unique identifier: NCT00159913.
Autoimmunity against pancreatic islets and other tissues before and after interferon-alpha therapy in patients with hepatitis C virus chronic infection.
Authors: C Betterle, P Fabris, R Zanchetta, B Pedini, G Tositti, E Bosi, F de Lalla
Journal: Diabetes Care (2000)

The aim of the study was to investigate the prevalence of clinical and latent autoimmune diseases in Italian patients with hepatitis C virus (HCV) chronic infection before and after treatment with interferon-alpha (IFN-alpha).The evidence of clinical autoimmune disease and the presence of autoantibodies were assessed in 70 patients with HCV chronic infection. Autoantibodies to islet cell (ICA), glucagon-producing cells (GCA), parietal cell (PCA), adrenal cortex (ACA), adrenal medulla (AdMA), nuclei (ANA), liver-kidney microsomal (LKM-Ab), mitochondrial, and smooth muscle (SMA) were tested using the classic indirect immunofluorescence technique. Autoantibodies to GAD (GADAb), second islet cell autoantigen (IA2-Ab), and insulin (IAA) were tested by radioimmunoassay and thyroid microsomal autoantibodies (TMHA) and thyroglobulin autoantibodies (TGHA) were assessed by hemoagglutination test.None of the 70 patients studied showed evidence of clinical disease before treatment with IFN-alpha. However, 1 (1.4%) patient was positive for ICA, 2 (2.8%) were positive for GCA, 2 (2.8%) for GADAb, 5 (7.1%) for PCA, 2 (2.8%) for ANA, 3 (3.7%) for SMA, 4 (5.7%) for TMHA, and 2 (2.8%) for TGHA. These frequencies were not significantly different when compared with healthy control subjects. There were 29 (41%) patients who were positive for IAA at low titers compared with 2% of the control subjects (significantly different P < 0.0001). ICA titers of one patient positive for ICA/GADAb increased during the IFN-alpha therapy, and the patient developed type 1 diabetes 5 months after the beginning of treatment. IAA levels did not change during the course of treatment, and none of the IAA+ patients developed diabetes. Thyroid autoantibody titers increased in 3 of the 4 initially positive patients, with 1 patient becoming positive and 2 thyroid antibody-positive patients developing overt hypothyroidism during IFN-alpha treatment. PCA titers increased in 1 of 5 positive patients. Antibodies to other autoantigens did not change during the course of treatment.We have not found an increased frequency of clinical or latent autoimmune diseases in patients with chronic HCV infection. However, this study suggests that screening patients for autoantibodies (in particular, thyroid and pancreas) before and during IFN-alpha therapy may be useful in assessing the risk of patients developing autoimmune disease.
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome
Authors: D L Worthley, K D Phillips, N Wayte, K A Schrader, S Healey, P Kaurah, A Shulkes, F Grimpen, A Clouston, D Moore, D Cullen, D Ormonde, D Mounkley, X Wen, N Lindor, F Carneiro, D G Huntsman, G Chenevix-Trench, G K Suthers
Journal: Gut (2011)

<h3>Objective</h3> The purpose of this study was the clinical and pathological characterisation of a new autosomal dominant gastric polyposis syndrome, gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). <h3>Methods</h3> Case series were examined, documenting GAPPS in three families from Australia, the USA and Canada. The affected families were identified through referral to centralised clinical genetics centres. <h3>Results</h3> The report identifies the clinical and pathological features of this syndrome, including the predominant dysplastic fundic gland polyp histology, the exclusive involvement of the gastric body and fundus, the apparent inverse association with current <i>Helicobacter pylori</i> infection and the autosomal dominant mode of inheritance. <h3>Conclusions</h3> GAPPS is a unique gastric polyposis syndrome with a significant risk of gastric adenocarcinoma. It is characterised by the autosomal dominant transmission of fundic gland polyposis, including areas of dysplasia or intestinal-type gastric adenocarcinoma, restricted to the proximal stomach, and with no evidence of colorectal or duodenal polyposis or other heritable gastrointestinal cancer syndromes.
Genome-wide expression profiling of T-cells in childhood wheeze
Authors: A. Bosco, P. G. Holt
Journal: European Respiratory Journal (2008)

<h3>Objectives</h3> To evaluate the cost-effectiveness of a work style (WS) intervention and a work style plus physical activity (WSPA) intervention in computer workers with neck and upper limb symptoms compared with usual care. <h3>Methods</h3> An economic evaluation was conducted from an employer9s perspective and alongside a randomised controlled trial in which 466 computer workers with neck and upper limb symptoms were randomised to a WS group (N=152), a WSPA group (N=156) or a usual care group (N=158). Total costs were compared to the effects on recovery and pain intensity. In the primary analyses, missing effect data were imputed using multiple imputation techniques. <h3>Results</h3> Total costs during the 12-month intervention and follow-up period were €1907 (WS), €2811 (WSPA) and €2310 (usual care). Differences between groups were not statistically significant. Neither intervention was more effective than usual care in improving overall recovery. The WS intervention was more effective than usual care in reducing current pain, average pain and worst pain in the past 4 weeks, but the WSPA intervention was not. The acceptability curve showed that when a company is willing to pay approximately €900 for a 1-point reduction in average pain (scale from 0 to 10), the probability of cost-effectiveness compared to usual care is 95%. Similar results were observed for current and worst pain. <h3>Conclusions</h3> This study shows that the WS intervention was not cost-effective for improving recovery but was cost-effective for reducing pain intensity, although this reduction was not clinically significant. The WSPA intervention was not cost-effective compared with usual care. <h3>Trial registration number</h3> ISRCTN87019406.
Regulation of Ventricular Contraction by the Carotid Sinus
Authors: S. J. SARNOFF, J. P. GILMORE, S. K. BROCKMAN, J. H. MITCHELL, R. J. LINDEN
Journal: Circulation Research (1960)

A lowering of pressure in the carotid sinus reflexly increases the force of atrial systole by (a) increasing sympathetic activity to the heart (carotido-sympatho-atrial reflex) and(b) decreasing efferent vagal activity to the heart (carotido-vago-atrial reflex); an elevation of carotid pressure has the reverse effect. The carotid sinus can thereby vary ventricular end-diastolic pressure and fiber length. A change of pressure in the carotid sinus reflexly modifies the ventricle's contractility such that from a given end-diastolic pressure or fiber length, with a low carotid pressure the ventricle's contraction will be substantially augmented and from a high carotid pressure it will be diminished. The role of the carotid sinus in circulatory regulation has been likened to a voltage regulating element in an electronic system; i.e., it causes an appropriate variation of input into the system so as to maintain a constant voltage when the current requirements of the system it is supplying are changed.
Association of an ERAP1 ERAP2 haplotype with familial ankylosing spondylitis
Authors: F. W. L. Tsui, N. Haroon, J. D. Reveille, P. Rahman, B. Chiu, H. W. Tsui, R. D. Inman
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objectives</h3> To assess whether there is excess transmission of alleles from the <i>ERAP1 ERAP2</i> locus in families with ankylosing spondylitis (AS). <h3>Methods</h3> 199 multiplex families with AS with four non-synonymous single nucleotide polymorphisms (SNPs), three in the endoplasmic reticulum aminopeptidase 1 (<i>ERAP1</i>) gene (<i>rs27044</i>, <i>rs10050860</i> and <i>rs30187</i>) and one in the endoplasmic reticulum aminopeptidase 2 (<i>ERAP2</i>) gene (<i>rs2549782</i>), were genotyped and family-based association analyses were performed. <h3>Results</h3> Family-based association testing (FBAT –e; empirical variance option) analysis showed that <i>ERAP1 rs30187[T]</i> was associated with AS (additive model: p<i>=</i>0.02; dominant model: p=0.007). Haplotype permutation tests (HBAT-p) showed that a haplotype in the <i>ERAP1</i> and <i>ERAP2</i> locus (<i>rs27044[G] rs30187[T] rs2549782[T]</i>) was significantly associated with AS (two-sided p value by permutation test 0.009 for additive and 0.008 for dominant model, respectively). <h3>Conclusion</h3> This study shows that one <i>ERAP1</i> SNP and a haplotype in the <i>ERAP1</i> and <i>ERAP2</i> locus are associated with familial AS.