tbuckley/cabot-search huggingface dataset:
Effect of captopril on the release of the components of the renin-angiotensin system into plasma and lymph.
Authors: C S Wilcox, V J Dzau
Journal: Journal of the American Society of Nephrology (1992)

The effects of captopril on the intrarenal renin-angiotensin system were assessed from measurements in arterial plasma, renal venous plasma, and renal lymph from salt-depleted dogs. In the basal state, immunoreactive angiotensin II (Ang II) in renal venous plasma averaged only 60 +/- 12% (P less than 0.01) of arterial plasma, although the concentration of Ang II in renal lymph was 2.0 +/- 0.4-fold (P less than 0.05) greater. The Ang II concentration of renal lymph incubated ex vivo at 37 degrees C doubled in 10 to 15 min, which was the time taken to collect renal lymph samples. Compared with arterial plasma, renal lymph contained lower concentrations (P less than 0.01) of renin substrate and angiotensin-converting enzyme but higher concentrations of active (5.3 +/- 2.1-fold) and inactive (8.9 +/- 3.2-fold) renin. Although captopril increased the secretion of active renin into renal venous plasma by six-fold, the secretion of total renin was unchanged because of a reciprocal fall in the secretion of inactive renin. The percent reduction in renal vascular resistance with captopril correlated with the percent fall in Ang II in renal lymph (r = 0.70). In conclusion: (1) all components of the renin-angiotensin system are represented in the renal interstitium, as reflected in lymph; (2) Ang II concentrations in renal lymph in vivo approximate arterial levels; (3) increased secretion of active renin into plasma during intrarenal infusion of captopril into denervated kidneys is due predominantly to renin activation; and (4) renal vascular resistance may depend on the concentration of Ang II in the renal interstitium.
An assessment of community health workers' ability to screen for cardiovascular disease risk with a simple, non-invasive risk assessment instrument in Bangladesh, Guatemala, Mexico, and South Africa: an observational study
Authors: Thomas A Gaziano, Shafika Abrahams-Gessel, Catalina A Denman, Carlos Mendoza Montano, Masuma Khanam, Thandi Puoane, Naomi S Levitt
Journal: The Lancet Global Health (2015)
Clinical relevance of transmembrane drug efflux as a mechanism of multidrug resistance.
Authors: D M Bradshaw, R J Arceci
Journal: Journal of Clinical Oncology (1998)

For cytotoxic agents to have an effect on tumor cells, drugs must first be transported into the cell, potentially be metabolized to an active form, and interact appropriately with target molecules. A final common pathway of cytotoxic agents is usually the initiation of programmed cell death, or apoptosis. Tumor cells overcome the effects of cytotoxic agents at one or more of these levels. The classic multidrug-resistance (MDR) phenotype, as mediated by the drug efflux pump, P-glycoprotein, is one of the most extensively studied mechanisms of drug resistance. Additional drug transporters, such as the multidrug resistance-associated proteins (MRPs), have also been identified and can convey drug-resistance phenotypes. Important questions remain as to how and whether such transport systems can be specifically measured and effectively targeted to improve therapeutic outcomes. Furthermore, alterations in drug targets, drug metabolism, repair of DNA damage caused by drugs, and the inability to initiate programmed cell death can all contribute to drug resistance and must be ultimately considered in the explanation of tumor-cell resistance to therapy. Continued exploration of the pharmacologic methods to circumvent drug resistance, as well as strategies that involve targeted therapy and immunomodulation, should increase the specificity and efficacy of treatments for patients with cancer.
A new rating scale for Alzheimer's disease
Authors: Wilma G. Rosen, Richard C. Mohs, Kenneth L. Davis
Journal: American Journal of Psychiatry (1984)

A new rating instrument, the Alzheimer's Disease Assessment Scale, was designed specifically to evaluate the severity of cognitive and noncognitive behavioral dysfunctions characteristic of persons with Alzheimer's disease. Item descriptions, administration procedures, and scoring are outlined. Twenty-seven subjects with Alzheimer's disease and 28 normal elderly subjects were rated on 40 items. Twenty-one items with significant intraclass correlation coefficients for interrater reliability (range, .650-.989) and significant Spearman rank-order correlation coefficients for test-retest reliability (range, .514-1) constitute the final scale. Subjects with Alzheimer's disease had significantly more cognitive and noncognitive dysfunction than the normal elderly subjects.
IL17 Functions through the Novel REG3β–JAK2–STAT3 Inflammatory Pathway to Promote the Transition from Chronic Pancreatitis to Pancreatic Cancer
Authors: Celine Loncle, Laia Bonjoch, Emma Folch-Puy, Maria Belen Lopez-Millan, Sophie Lac, Maria Inés Molejon, Eduardo Chuluyan, Pierre Cordelier, Pierre Dubus, Gwen Lomberk, Raul Urrutia, Daniel Closa, Juan L. Iovanna
Journal: Cancer Research (2015)

Pancreatic ductal adenocarcinoma (PDAC) offers an optimal model for discovering "druggable" molecular pathways that participate in inflammation-associated cancer development. Chronic pancreatitis, a common prolonged inflammatory disease, behaves as a well-known premalignant condition that contributes to PDAC development. Although the mechanisms underlying the pancreatitis-to-cancer transition remain to be fully elucidated, emerging evidence supports the hypothesis that the actions of proinflammatory mediators on cells harboring Kras mutations promote neoplastic transformation. Recent elegant studies demonstrated that the IL17 pathway mediates this phenomenon and can be targeted with antibodies, but the downstream mechanisms by which IL17 functions during this transition are currently unclear. In this study, we demonstrate that IL17 induces the expression of REG3β, a well-known mediator of pancreatitis, during acinar-to-ductal metaplasia and in early pancreatic intraepithelial neoplasia (PanIN) lesions. Furthermore, we found that REG3β promotes cell growth and decreases sensitivity to cell death through activation of the gp130-JAK2-STAT3-dependent pathway. Genetic inactivation of REG3β in the context of oncogenic Kras-driven PDAC resulted in reduced PanIN formation, an effect that could be rescued by administration of exogenous REG3β. Taken together, our findings provide mechanistic insight into the pathways underlying inflammation-associated pancreatic cancer, revealing a dual and contextual pathophysiologic role for REG3β during pancreatitis and PDAC initiation.
A Phase || Trial of First-Line Nab-Paclitaxel/Carboplatin Versus Gemcitabine/Carboplatin in Advanced Squamous Cell Carcinoma of the Lung (Ctong1002)
Authors: J. Yang, C. Huang, Y. Song, Y. Cheng, G. Chen, H. Yan, Q. Zhou, H. Chen, H. Chen, X. Zhang, Y. Wu, X. Ben
Journal: Annals of Oncology (2014)

Aim: The administration of nab-paclitaxel/carboplatin (nab-PC) as first-line therapy in patients with advanced non-small-cell lung cancer was efficacious and resulted in a significantly improved objective overall response rate (ORR) versus solvent-based PC in a phase ||| trial.Subgroup analysis showed the squamous histology appeared to be a predictive factor to nab-paclitaxel treatment.This phase || trial (NCT01236716; CTONG1002) compared the eficacy and safety of first-line
Evaluation of cardiopulmonary effects and oxidative stress in sugarcane workers compared to a control population exposed to outdoor biomass air pollution
Authors: Gustavo Prado, Ubiratan Santos, Mário Terra-Filho, Dirce Zanetta, Renato Paceli
Journal: European Respiratory Journal (2011)

Brazil is the world's largest producer of sugar and alcohol. The practice of burning the sugarcane field in the night before harvesting in order to facilitate cropping and thereby increase productivity is still very common. This biomass burning emits large amounts of particulate (PM) and gaseous pollutants to the atmosphere.

With the aim of studying cardiopulmonary impacts and oxidative stress in a population of 113 sugarcane workers (SW) and 109 local healthy controls (C), we evaluated lung function tests (LFTs), blood pressure (BP), heart rate variability (HRV) – in submaximal treadmill protocol – and laboratory tests in pre-harvest and harvest periods. All subjects were male non-smokers. Data were submited to univariate and LMM multivariate analysis.

Results: Median age was 28.4 (C) and 23 (SW); P=0.02.

In the harvest period (median atmospheric PM2.5=75.3μg/m3 in sugarcane tillage area vs 27.7μg/m3 in city area) there was a significant higher increase in CPK levels in SW than in control subjects, as well as a higher reduction in LFTs. We also found a significant higher increase in diastolic BP and decrease in HRV among sugarcane workers in harvest period. Another important result, was the statistically significant reduction in antioxidants enzymes SOD, GST and GPX in the harvest period, much more expressive among sugarcane workers than in control subjects.

We conclude, therefore, that even in healthy populations, exposure to biomass outdoor pollution can cause cardiopulmonary detrimental effects with potential clinical relevance and that such impacts can be probably explained by the physiopathologic pathway of oxidative stress.
Magnetic Resonance Imaging of the Nose and Paranasal Sinuses
Authors: G A S Lloyd
Journal: Journal of the Royal Society of Medicine (1989)

Seventy-five patients with a wide range of sinus disease have been investigated by magnetic resonance (MR): these included congenital conditions, allergic and inflammatory sinus disease, fungus infections, and the necrotizing granulomata. In addition, a variety of benign and malignant tumours have been examined, and in the more recent sinus malignancies the paramagnetic contrast agent, Gadolinium (Gd) DTPA (Schering Health Care) has been used. This experience of magnetic resonance scanning has shown that it is superior to computed tomography in demonstrating the extent of malignant disease in the nose and sinuses; most especially when Gd DTPA is used, reaching an accuracy of over 96% by biopsy correlation. An additional advantage of this technique is the wide coverage of the head and neck for the assessment of malignant disease, provided by direct 3 plane imaging and the multislice facility. The main disadvantage of magnetic resonance of the sinuses is the poor demonstration of calcification and bone. For this reason the MR scans may need to be augmented by high resolution CT performed specifically to show bone detail.
Allergen-induced late-phase airways obstruction in the pig: the role of endogenous cortisol
Authors: C Fornhem, JM Lundberg, K Alving
Journal: European Respiratory Journal (1995)

In developing a novel model for studies of the allergen-induced late-phase airways obstruction, by using the pig, the importance of endogenous cortisol levels was examined by the use of metyrapone, a cortisol-synthesis inhibitor. Specific-pathogen free pigs were actively sensitized with Ascaris suum allergen. One group of pigs was treated with a constant infusion of metyrapone in order to maintain low levels of plasma cortisol. Ascaris suum allergen was nebulized into the lower airways and plasma cortisol and catecholamine levels, total lung resistance and dynamic compliance, blood gases and pH, and blood flow in the bronchial circulation were continuously recorded for 8 h. At the time of allergen challenge, the plasma cortisol levels in sensitized pigs were 455 +/- 37 nM and 40.1 +/- 3.8 nM in non-metyrapone-treated and metyrapone-treated pigs, respectively. No difference was seen between the magnitude of the acute bronchoconstrictor response in the two groups. A late airways obstruction, starting at about 4 h, developed only in pigs with low cortisol levels, whereas a late increase in blood flow in the bronchial circulation was seen in both groups, even if a late airways obstruction was absent. Plasma adrenaline did not seem to influence the late-phase reaction. These results suggest that endogenous cortisol levels, but not adrenaline, modify the late response to allergen in the pig. Furthermore, it is suggested that the pig is a suitable model for studies of allergic reactions in the airways, if metyrapone is used to keep plasma cortisol levels within a normal range.
Fluorine Substitution as a Probe for the Role of the 6-Position of Benzo[&lt;italic&gt;a&lt;/italic&gt;]pyrene in Carcinogenesis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: M K Buening, W Levin, A W Wood, R L Chang, I Agranat, M Rabinovitz, D R Buhler, H D Mah, O Hernandez, R B Simpson, D M Jerina, A H Conney, E C Miller, J A Miller
Journal: JNCI Journal of the National Cancer Institute (1983)

The tumorigenic activities of benzo[a]pyrene (BP) and 6-fluorobenzo[a]pyrene (6-F-BP) were compared to determine whether an unsubstituted 6-position is important for the carcinogenic effect of BP. Highly purified samples of 6-F-BP and BP had similar activities for the induction of lung adenomas in Swiss Webster mice treated before weaning. The 6-fluoro derivative, however, had about one-half as much activity as BP for the initiation of skin papillomas in CD-1 mice. Similarly, 6-F-BP (≈90% purity) had about one-half the activity of BP for the induction of skin tumors in C57BL/6J mice given repetitive treatments of the hydrocarbons and for the induction of sarcomas in C3H/fCum mice given a single sc injection. 6-F-BP (≈90% purity) had activity similar to that of BP for induction of sarcomas at the sc injection site in Fischer 344 rats. These results and related data indicate the need for detailed metabolic studies whenever fluorine substitution is used as a probe to assess the role of the unsubstituted position in the carcinogenicity of the parent compound.
LSC 2012 abstract - Wnt11 is identified in 3D human lung tissue model as regulator of distal airway epithelial cell differentiation
Authors: Domokos Bartis, Veronika Csongei, Vijay D'Souza, David R. Thickett, Judit E. Pongracz
Journal: European Respiratory Journal (2012)

Alveolar Type II (ATII) cells repopulate the damaged alveolar surface and transdifferentiate into Alveolar Type I (ATI) cells during physiological regeneration. During pathological airway repair excessive Epithelial-Mesenchymal Transition (EMT) might occur, resulting in fibrosis. Mesenchymal signals might contribute to the differentiation and regeneration of pulmonary epithelium stimulating distal airway epithelial differentiation and preventing EMT. To identify these factors, we constructed a 3-dimensional (3D) human tissue model of primary pulmonary cells to mimic epithelial-mesenchymal interactions in the human lung.  Distal airway epithelial cells differentiate into ATII-like cells as suggested by morphological changes as well as increased expression of differentiation markers AQP3, SP-A, SP-C in the 3D model. Wnt11 was identified in the model and in human lung explant cultures as one of the main regulators of ATII differerentiation. Added Wnt11 increased the expression of ATII markers, while silencing of Wnt11 resulted in elevated levels of EMT markers N-cadherin and S100A4. We conclude that the 3D lung model is applicable for studying epithelial-mesenchymal interactions in the lung. Our finding may mark Wnt11 as a potential therapeutic target in lung regenerative therapy.
Trends in diagnosis and long-term treatment of patients with asthma in primary health care facilities (1998-2011) in Saint-Petersburg, Russia
Authors: Alexander Emelyanov, Inessa Tsukanova, Gleb Fedoseev, Galina Sergeeva, Natalia Lisitsyna, Lubov Bakanina, Ekaterina Nikitina
Journal: European Respiratory Journal (2013)

Background. This study was performed to assess the changes in diagnosis and treatment of asthma (1998-2011) in primary health care facilities in Saint-Petersburg, the second largest city in Russia.  Methods. Case record forms (CRF) of 1248 outpatients 18 to 89 years old with asthma were reviewed in 13 outpatient departments in 7 residential areas in Saint Petersburg in 1998, 2002 and 2005 (253, 579 and 416 respectively) and the telephone interviews with 205 asthma outpatients (aged 24 to 90 yrs) were conducted in 2011. Asthma control was assessed by using the Asthma Control Test™ (ACT) in 2011.  Results. During the past 12 month spirometry were performed in 81.3% of patients in 2002 and only 62.1%, 50.7% and 26.8% in 1998, 2005 and 2011 respectively (p  Conclusion. Quality of diagnostics and treatment of asthma in primary health care is not sufficient and should be improved. Asthma pharmacotherapy has been changed in the past 13 years according to evidence-based guidelines.
Granulocytic myeloid-derived-supressor cells (GrMDSCs) in chronic obstructive pulmonary disease (COPD) patients
Authors: Agata Nowicka, Beata Brajer-Luftmann, Mariusz Kaczmarek, Halina Batura-Gabryel
Journal: European Respiratory Journal (2013)

COPD increses the risk of developing lung cancer (LC). Development of LC may be connected not only with smoking, but also with genetic predysposition and chronic inflammation. GrMDSCs expand in cancer, inflamation and infection. GrMDSCs activation increses immunosupresive factors expression, that may activate epithelial cells proliferation and support their migration. These processes may lead to neoplasmatic transformation in course of COPD.

Aim of the study: assesment of GrMDSCs in COPD patients blood and BAL (bronchoalveolar lavage) and correlation with clinical parameteres. 18 COPD patients were included to cross-sectional study. Immunophenotyping of blood and BAL cells was performed using CD11b, CD33, Lin1, HLA-DR, CD45 (FACSCanto cytometer). PFTs (pulmonary functin tests) and BODE index were performed.

Results: We indicated the presence of GrMDSCs in COPD patients blood (Mean 2.75%, SD 1.625, Min. 0.31, Max. 5.23) and BAL (Mean 0.21%, SD 0.459, Min. 0.0, Max. 1.71). We observed correlation between GrMDSCs\[%] and age [yr\] (rs,0,68, p 0,0099) GOLD stage (rs,0,7, p 0,0080), RV\[%\] (rs,0,64, p 0,0182), RV/TLC (rs,0,74, p 0,0036) in BAL and between GrMDSCs\[%] and age[yr\] (rs,-0,63, p 0,0223), paO2\[mmHg\] (rs,0,57, p 0,0398), FVC\[%\] (rs,0,66, p 0,0142) in blood. No correlation between GrMDSCs[%] and other PFT parametres (FEV1, TLC, SaO2, paCO2, DLCO), and BODE index was observed.

Conclusion: Our findings confirm the presence of GrMDSCs in systemic and local inflammatory process in COPD. Further studies are needed to explain their role in neoplasmatic transformation in course of COPD.
Early management of severe acute biliary pancreatitis: wind of change
Authors: M S Petrov
Journal: Gut (2008)

In a recent issue of Gut , I read with interest the guidelines on the management of common bile duct stones by Williams et al ( Gut 2008;57:1004–21) and would like to thank the authors for providing these recommendations. However, I have some comments with regard to the management of common bile duct stones in the setting of acute biliary pancreatitis (ABP).

The authors state that “patients with (predicted) severe pancreatitis of suspected or proven biliary origin should undergo biliary sphincterotomy ± endoscopic stone extraction within 72 h of presentation”. Generally, this recommendation reflects the literature published until 2005. However, some more recent randomised controlled trials (RCTs)1 2 and a meta-analysis3 escaped the attention of Dr Williams and his colleagues. In particular, the recent meta-analysis found that co-existing acute cholangitis …
Rapid susceptibility testing of Mycobacterium tuberculosis by the Mycobacteria Growth Indicator Tube (MGITAST SIRE)
Authors: E.A. Macondo, F. Ba, A. Gaye-Diallo, N.C. Touré-Kane, O. Kaıré, A. Gueye-Ndiaye, C.S. Boye, S. Mboup
Journal: Clinical Microbiology and Infection (2000)
Molecular Tumor Testing for Lynch Syndrome in Patients With Colorectal Cancer
Authors: Jeremy Matloff, Aimee Lucas, Alexandros D. Polydorides, Steven H. Itzkowitz
Journal: Journal of the National Comprehensive Cancer Network (2013)

Lynch syndrome (LS) is the most common hereditary colon cancer syndrome, and accounts for 2% to 3% of all colorectal cancers. These tumors are caused by germline mutations of DNA mismatch repair genes, which result in microsatellite instability. Colonic and extracolonic malignancies can occur at a young age, and are often diagnosed at a late stage because of underrecognition of the syndrome. Identifying individuals with LS before the development of these malignancies decreases mortality because of frequent screening and surveillance of colonic and extracolonic cancers. Moreover, family members of these individuals can be tested and begin screening at a young age if appropriate. Classically, Amsterdam criteria and Bethesda guidelines have been used to identify at-risk individuals; however, these tools miss a significant number of cases. As the molecular basis for LS has been clarified, more sophisticated strategies have emerged. Testing all colorectal cancers for loss of mismatch repair proteins, known as universal screening, is a strategy used to identify individuals at risk for LS. This approach has been shown to be more sensitive than previous methods that rely on family history. Implementation of universal tumor testing necessitates a systematic approach to positive results in order to have maximal effect, and could prove to be the most cost-effective approach to reducing cancer mortality in patients with LS.
Analysis of 177 endobronchial tuberculosis cases in Serbia over 15-years period
Authors: Dragana Jovanovic, Ljiljana Denic-Markovic, Natalija Samardzic, Spasoje Popevic, Vesna Skodric-Trifunovic, Marina Roksandic Milenkovic, Ruza Stevic, Marta Velinovic, Jelena Stojsic, Nada Vasic, Milica Kontic, Dragana Maric
Journal: European Respiratory Journal (2012)

Introduction:  Tuberculosis still represents a significant health problem of population in Serbia, the incidence being for last few decades 32-36/100.000 inhabitants, up to last few years when it decreased to 24-26. Endobronchial tuberculosis (EBTB) is a chronic, progressive tuberculosis infection with often complicated clinical course and bronchostenosis formation.   The aim  of the study was to determine common clinical features and diagnostic aspects of bronchoscopic biopsy proven EBTB in population of Serbia over 15 years period and compare with published data.   Method : Analysis and comparison of clinical features, radiologic, mycobacterial, bronchoscopic and histologic findings of 177 EBTB patients by SPSS ver. 15 for Windows, chi-square test, t - test and calculating Phi correlation coefficient.   Results : Male to female ratio was 1.2:1. Five patients (2.8%) were asymptomatic. None had normal chest radiograph finding; the most frequent localization of concurrent pulmonary TB lesions was in the upper lobes. Two thirds of patients, 116 (65.5%) had cavernous lesions. Atypical TB was evident in 27pts (15.3%).  The most common endoscopic forms of EBTB were edematous hyperemic (40,1%) and non-specific bronchitis (35,6%) unlike majority of published data. Bacteriologic confirmation of TB had 117 patients (66.1%). Sputum cultures for AFB were positive in only 27.7%, bronchial washing culture in 10.1%. Sputum and bronchial washing culture both were positive in 28.2% patients. Correlation between bronchoscopic categories of EBTB and bacteriologic confirmation of TB diagnosis was analysed and discussed.   Conclusion : EBTB in Serbia has some distinctive and specific features in comparison with other published EBTB series.
Necrotizing soft tissue infections caused by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis of groups C and G in western Norway
Authors: T. Bruun, B.R. Kittang, B.J. de Hoog, S. Aardal, H.K. Flaatten, N. Langeland, H. Mylvaganam, H.A. Vindenes, S. Skrede
Journal: Clinical Microbiology and Infection (2013)