tbuckley/cabot-search huggingface dataset:
Distribution of immunocompetent cells in the bronchial wall of clinically healthy subjects showing bronchial hyperresponsiveness.
Authors: C Power, S Sreenan, B Hurson, C Burke, L W Poulter
Journal: Thorax (1993)

BACKGROUND--Nearly all asthmatic subjects show bronchial hyperresponsiveness, in that the provocative concentration of histamine reducing forced expiratory volume in one second (FEV1) by 20% (PC20FEV1) is &lt; or = 8 mg/ml histamine, and have underlying chronic inflammation of the bronchial wall mediated by T cells. The possible cause and effect relationship between these phenomena remains an enigma. As a proportion of clinically healthy subjects show bronchial hyperresponsiveness, this study was undertaken to determine whether they also show evidence of bronchial inflammation. METHODS--Bronchial biopsy specimens were obtained from 27 clinically healthy subjects with no history of lung disease. Samples were taken perioperatively before elective knee arthroscopy for sports injuries. Specimens were frozen and cryostat sections analysed immunocytochemically with monoclonal antibodies to identify the presence of T lymphocytes, antigen presenting cells, and the expression of HLA-DR. Double immunofluorescence studies were performed with monoclonal antibodies RFD1 and RFD7 to show the relative proportions of RFD1+ RFD7- antigen presenting cells, RFD1- RFD7+ mature phagocytes, and RFD1+ RFD7+ suppressor macrophages. Histological stains were performed to show the presence of eosinophils and mast cells. Three to four weeks after bronchoscopy spirometry was performed on these subjects to record FEV1, forced vital capacity (FVC), FEV1/FVC, and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75). Bronchial hyperreactivity was recorded by determining PC20FEV1 to histamine. RESULTS--Nine of the 27 subjects showed bronchial hyperresponsiveness as defined by a PC20FEV1 of &lt; or = 8 mg/ml histamine. Segregated subjects with and without bronchial hyperresponsiveness showed no difference in spirometric results. Immunohistological analysis showed no evidence of inflammation in either group. Numbers of T cells, eosinophils, and mast cells were the same in both groups as was the expression of HLA-DR antigen. No neutrophils were observed in any tissues. Interestingly, reduced numbers of macrophages with the phenotype of antigen presenting cells (monoclonal antibodies RFD1+ RFD7-) were recorded in the subjects with bronchial hyperresponsiveness, who also had a significant increase in the proportion of RFD1+ RFD7+ suppressor macrophages. CONCLUSIONS--Up to 30% of selected clinically healthy subjects may have a PC20FEV1 of &lt; or = 8 mg/ml histamine. This physiological trait can exist in the absence of bronchial inflammation. This suggests that bronchial hyperresponsiveness as currently defined is not dependent on immunopathological changes in the bronchial wall and does not necessarily promote even subclinical inflammation.
Combination of Protein Coding and Noncoding Gene Expression as a Robust Prognostic Classifier in Stage I Lung Adenocarcinoma
Authors: Ichiro Akagi, Hirokazu Okayama, Aaron J. Schetter, Ana I. Robles, Takashi Kohno, Elise D. Bowman, Dickran Kazandjian, Judith A. Welsh, Naohide Oue, Motonobu Saito, Masao Miyashita, Eiji Uchida, Toshihiro Takizawa, Seiichi Takenoshita, Vidar Skaug, Steen Mollerup, Aage Haugen, Jun Yokota, Curtis C. Harris
Journal: Cancer Research (2013)

Prognostic tests for patients with early-stage lung cancer may provide needed guidance on postoperative surveillance and therapeutic decisions. We used a novel strategy to develop and validate a prognostic classifier for early-stage lung cancer. Specifically, we focused on 42 genes with roles in lung cancer or cancer prognosis. Expression of these biologically relevant genes and their association with relapse-free survival (RFS) were evaluated using microarray data from 148 patients with stage I lung adenocarcinoma. Seven genes associated with RFS were further examined by quantitative reverse transcription PCR in 291 lung adenocarcinoma tissues from Japan, the United States, and Norway. Only BRCA1, HIF1A, DLC1, and XPO1 were each significantly associated with prognosis in the Japan and US/Norway cohorts. A Cox regression-based classifier was developed using these four genes on the Japan cohort and validated in stage I lung adenocarcinoma from the US/Norway cohort and three publicly available lung adenocarcinoma expression profiling datasets. The results suggest that the classifier is robust across ethnically and geographically diverse populations regardless of the technology used to measure gene expression. We evaluated the combination of the four-gene classifier with miRNA miR-21 (MIR21) expression and found that the combination improved associations with prognosis, which were significant in stratified analyses on stage IA and stage IB patients. Thus, the four coding gene classifier, alone or with miR-21 expression, may provide a clinically useful tool to identify high-risk patients and guide recommendations regarding adjuvant therapy and postoperative surveillance of patients with stage I lung adenocarcinoma.
Subconjunctival Hemorrhage and Conjunctivochalasis
Authors: Tatsuya Mimura, Tomohiko Usui, Satoru Yamagami, Hideharu Funatsu, Hidetaka Noma, Norihiko Honda, Shima Fukuoka, Rika Shirakawa, Hiroshi Hotta, Shiro Amano
Journal: Ophthalmology (2009)
A randomized double-blind multicenter phase III study offixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy
Authors: M.D. Green, H. Koelbl, J. Baselga, A. Galid, V. Guillem, P. Gascon, S. Siena, R.I. Lalisang, H. Samonigg, M.R. Clemens, V. Zani, B.C. Liang, J. Renwick, M.J. Piccart
Journal: Annals of Oncology (2002)
Surgery for nonsmall cell lung cancer: can improvements be made?
Authors: S.G. Spiro
Journal: European Respiratory Journal (2003)

Low-dose spiral computed tomography (CT) for the earlier detection of lung cancer is at the stage of producing hypothesis-generating studies. These studies have shown that more cancers are found at a favourable stage (IA) in prevalence screening but that the fewer numbers found in incidence screening tend to have a slightly worse stage. Randomised controlled trials will be necessary to resolve the place of spiral CT screening. The role of neo-adjuvant chemotherapy before surgery in nonsmall cell lung cancer looks less promising than suggested by earlier studies and the place of adjuvant chemotherapy following surgery appears to be unhelpful, although results of some large, randomised international studies are still awaited. Radical radiotherapy is a poor alternative to surgery in resectable patients who refuse or are unfit for surgery and postoperative radiotherapy is detrimental. Positron emission tomography scanning offers a genuine opportunity to identify occult disease and improve staging prior to surgery and therefore save futile thoracotomies in ∼20% of patients otherwise apparently suitable for resection.
Downregulation of FOXO3a Promotes Tumor Metastasis and Is Associated with Metastasis-Free Survival of Patients with Clear Cell Renal Cell Carcinoma
Authors: Dong Ni, Xin Ma, Hong-Zhao Li, Yu Gao, Xin-Tao Li, Yu Zhang, Qing Ai, Peng Zhang, Er-Lin Song, Qing-Bo Huang, Yang Fan, Xu Zhang
Journal: Clinical Cancer Research (2014)

To explore the mechanisms underlying clear-cell renal cell carcinoma (ccRCC) metastasis using transcriptional profiling and bioinformatics analysis of ccRCC samples, and to elucidate the role of FOXO3a in ccRCC metastasis.Gene expression profiling was performed using four primary metastatic and five primary nonmetastatic ccRCC samples. The mRNA and protein levels of FOXO3a in ccRCC samples were investigated by real-time reverse transcription PCR and immunohistochemistry, respectively. The association between metastasis-free survival of patients with ccRCC and FOXO3a mRNA levels was analyzed. Biologic functions of FOXO3a in renal cancer cell lines were investigated. The influence of FOXO3a on tumor metastasis was also studied in vivo orthotopic xenograft tumor model. Finally, the mechanism by which FOXO3a attenuation could increase invasion and migration of tumor cells was explored.Bioinformatics analysis of the profiling data identified FOXO3a as a key factor in ccRCC metastasis. FOXO3a expression was decreased in primary metastatic ccRCC samples. Patients with low FOXO3a mRNA levels had poor metastasis-free survival (P = 0.003). Knocking down FOXO3a induced tumor cell invasion and migration in the nonmetastatic ccRCC cells. Induced FOXO3a overexpression in SN12-PM6 cells could inhibit tumor metastasis in vivo. Downregulation of FOXO3a increased SNAIL1 expression, thereby activating the epithelial-mesenchymal transition (EMT) of RCC cell lines.The loss of FOXO3a induced EMT of tumor cells by upregulating SNAIL1, which promoted tumor cells metastasis in vitro and in vivo. Thus, FOXO3a could be considered as an independent prognostic factor in ccRCC metastasis and could be a marker of occult metastases.
Occupational asthma to spores of Pleurotus cornucopiae
Authors: A Michils, P De Vuyst, N Nolard, G Servais, J Duchateau, JC Yernault
Journal: European Respiratory Journal (1991)

We report the case of a young man who developed severe asthma a few months after starting work in a factory producing a single type of mushroom: Pleurotus cornucopiae (a basidiomycete). Immunological investigations, performed with material recovered from the filtering devices of the mushroom's bed, led to demonstration of specific IgE and IgG against spore extracts and to isolation of one discriminant antigen (molecular weight: 10.5 kd). Current data concerning the underestimated role of the basidiomycetes in allergic asthma are reviewed.
Statin Use and Adrenal Aldosterone Production in Hypertensive and Diabetic Subjects
Authors: Rene Baudrand, Luminita H. Pojoga, Anand Vaidya, Amanda E. Garza, Paul A. Vöhringer, Xavier Jeunemaitre, Paul N. Hopkins, Tham M. Yao, Jonathan Williams, Gail K. Adler, Gordon H. Williams
Journal: Circulation (2015)

Background— Statins substantially reduce cardiovascular mortality and appear to have beneficial effects independent of their lipid-lowering properties. We evaluated the hypothesis that statin use may modulate the secretion of aldosterone, a well-known contributor to cardiovascular disease. Methods and Results— We measured adrenal hormones in 2 intervention studies. In study 1 in hypertensive subjects, aldosterone was analyzed at baseline and after angiotensin II stimulation on both high- and low-sodium diets (1122 observations, 15% on statins for &gt;3 months). Statin users had 33% lower aldosterone levels in adjusted models ( P &lt;0.001). Cortisol was not modified by statins. In secondary analyses, the lowest aldosterone levels were seen with lipophilic statins and with higher doses. Statin users had lower blood pressure and reduced salt sensitivity of blood pressure (both P &lt;0.001). In study 2, aldosterone was measured in diabetic patients on a high-sodium diet, before and after angiotensin II stimulation (143 observations, 79% statin users). Again, statin users had 26% lower aldosterone levels ( P =0.006), particularly those using lipophilic statins. Ex vivo studies in rat adrenal glomerulosa cells confirmed that lipophilic statins acutely inhibited aldosterone, but not corticosterone, in response to different secretagogues. Conclusions— Statin use among hypertensive and diabetic subjects was associated with lower aldosterone secretion in response to angiotensin II and a low-sodium diet in 2 human intervention studies. This effect appeared to be most pronounced with lipophilic statins and higher doses. Future studies to evaluate whether aldosterone inhibition may partially explain the robust cardioprotective effects of statins are warranted.
Antibiotic Treatment of <i>Mycobacterium abscessus</i> Lung Disease
Authors: Kyeongman Jeon, O Jung Kwon, Nam Yong Lee, Bum-Joon Kim, Yoon-Hoh Kook, Seung-Heon Lee, Young Kil Park, Chang Ki Kim, Won-Jung Koh
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: The optimal therapeutic regimen and duration of treatment for Mycobacterium abscessus lung disease is not well established.Objectives: To assess the efficacy of a standardized combination antibiotic therapy for the treatment of M. abscessus lung disease.Methods: Sixty-five patients (11 males, 55 females, median age 55 yr) with M. abscessus lung disease were treated with clarithromycin, ciprofloxacin, and doxycycline, together with an initial regimen of amikacin and cefoxitin for the first 4 weeks of hospitalization.Measurements and Main Results: Treatment response rates were 83% for symptoms and 74% for high-resolution computed tomography. Sputum conversion and maintenance of negative sputum cultures for more than 12 months was achieved in 38 (58%) patients. These rates were significantly lower in patients whose isolates were resistant to clarithromycin (17%, 2/12) compared with those whose isolates were susceptible or intermediate to clarithromycin (64%, 21/33; P = 0.007). Neutropenia and thrombocytopenia associated with cefoxitin developed in 33 (51%) and 4 (6%) patients, respectively. Drug-induced hepatotoxicity occurred in 10 (15%) patients. Because of these adverse reactions, cefoxitin was discontinued in 39 (60%) patients after treatment for a median of 22 days.Conclusions: Standardized combination antibiotic therapy was moderately effective in treating M. abscessus lung disease. However, frequent adverse reactions and the potential for long-duration hospitalization are important problems that remain to be solved.
Future Intervention Trials in Type 1 Diabetes
Authors: Terry Wilkin, Johnny Ludvigsson, Carla Greenbaum, Jerry Palmer, Dorothy Becker, Jan Bruining
Journal: Diabetes Care (2004)

The recently completed trials using insulin (U.S.) and nicotinamide (Europe) were not effective in preventing type 1 diabetes (1,2), but they leave an important legacy of goodwill among their collaborators and expertise in the conduct of such trials and a network through which more may be carried out.

A commentary on the trials has recently been published (3), and its authors urge “a different combination.” Concerned that too little is known of early immune interactions to intervene effectively in infancy, when the disease is thought to start, they propose trials of combination or “cocktail” therapy to achieve immunosuppression in new-onset patients. The ultimate benefit to the pre-diabetic patient would come if it were possible to improve β-cell survival in the context of reduced inflammation. Antigen-based therapies, monoclonal antibodies, and other immunoregulatory and immunosuppressive agents are listed, built around confident assertions that type 1 diabetes “has an autoimmune basis” and that, given the success of combination therapy in cancer, AIDS, and systemic lupus erythematosus, “why should type 1 diabetes be any different?”

But what if type 1 diabetes is different? What if the paradigms are different? And they may be because, despite an immense research effort, the doubling of type 1 diabetes over the past 25 …
The Effect of Including C-Reactive Protein in Cardiovascular Risk Prediction Models for Women
Authors: Nancy R. Cook, Julie E. Buring, Paul M Ridker
Journal: Annals of Internal Medicine (2006)

Background: While high-sensitivity C-reactive protein (hsCRP) is an independent predictor of cardiovascular risk, global risk prediction models incorporating hsCRP have not been developed for clinical use. Objective: To develop and compare global cardiovascular risk prediction models with and without hsCRP. Design: Observational cohort study. Setting: U.S. female health professionals. Participants: Initially healthy nondiabetic women age 45 years and older participating in the Women's Health Study and followed an average of 10 years. Measurements: Incident cardiovascular events (myocardial infarction, stroke, coronary revascularization, and cardiovascular death). Results: High-sensitivity CRP made a relative contribution to global risk at least as large as that provided by total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol individually, but less than that provided by age, smoking, and blood pressure. All global measures of fit improved when hsCRP was included, with likelihood-based measures demonstrating strong preference for models that include hsCRP. With use of 10-year risk categories of 0% to less than 5%, 5% to less than 10%, 10% to less than 20%, and 20% or greater, risk prediction was more accurate in models that included hsCRP, particularly for risk between 5% and 20%. Among women initially classified with risks of 5% to less than 10% and 10% to less than 20% according to the Adult Treatment Panel III covariables, 21% and 19%, respectively, were reclassified into more accurate risk categories. Although addition of hsCRP had minimal effect on the c-statistic (a measure of model discrimination) once age, smoking, and blood pressure were accounted for, the effect was nonetheless greater than that of total, LDL, or HDL cholesterol, suggesting that the c-statistic may be insensitive in evaluating risk prediction models. Limitations: Data were available only for women. Conclusions: A global risk prediction model that includes hsCRP improves cardiovascular risk classification in women, particularly among those with a 10-year risk of 5% to 20%. In models that include age, blood pressure, and smoking status, hsCRP improves prediction at least as much as do lipid measures.
Liver iron concentration measurements by MRI in chronically transfused children with sickle cell anemia: baseline results from the TWiTCH trial
Authors: John C. Wood, Sara Pressel, Zora R. Rogers, Isaac Odame, Janet L. Kwiatkowski, Margaret T. Lee, William C. Owen, Alan R. Cohen, Timothy St. Pierre, Matthew M. Heeney, William H. Schultz, Barry R. Davis, Russell E. Ware
Journal: American Journal of Hematology (2015)

Noninvasive, quantitative, and accurate assessment of liver iron concentration (LIC) by MRI is useful for patients receiving transfusions, but R2 and R2* MRI techniques have not been systematically compared in sickle cell anemia (SCA). We report baseline LIC results from the TWiTCH trial, which compares hydroxyurea with blood transfusion treatment for primary stroke prophylaxis assessed by transcranial Doppler sonography in pediatric SCA patients. Liver R2 was collected and processed using a FDA-approved commercial process (FerriScan®), while liver R2* quality control and processing were performed by a Core Laboratory blinded to clinical site and patient data. Baseline LIC studies using both MRI techniques were available for 120 participants. LICR2* and LICR2 results were highly correlated (r(2) = 0.93). A proportional bias of LIC(R2*)/LIC(R2), decreasing with average LIC, was observed. Systematic differences between LICR2* and LICR2 were also observed by MRI manufacturer. Importantly, LICR2* and LICR2 estimates had broad 95% limits of agreement with respect to each other. We recommend LICR2 and LICR2* not be used interchangeably in SCA patients to follow individual patient trends in iron burden.
Ability to Acquire Drug Resistance Arises Early during the Tumorigenesis Process
Authors: Ernesto Yagüe, Ana Arance, Loïc Kubitza, Michael O'Hare, Parmjit Jat, Caroline M. Ogilvie, Ian R. Hart, Christopher F. Higgins, Selina Raguz
Journal: Cancer Research (2007)

Abstract Resistance to chemotherapy is one of the principal causes of cancer mortality and is generally considered a late event in tumor progression. Although cellular models of drug resistance have been useful in identifying the molecules responsible for conferring drug resistance, most of these cellular models are derived from cell lines isolated from patients at a late stage in cancer progression. To ask at which stage in the tumorigenic progression does the cell gain the ability to acquire drug resistance, we generated a series of pretumorigenic and tumorigenic cells from human embryonic skin fibroblasts by introducing, sequentially, the catalytic subunit of telomerase, SV40 large T and small T oncoproteins, and an oncogenic form of ras. We show that the ability to acquire multidrug resistance (MDR) can arise before the malignant transformation stage. The minimal set of changes necessary to obtain pretumorigenic drug-resistant cells is expression of telomerase and inactivation of p53 and pRb. Thus, the pathways inactivated during tumorigenesis also confer the ability to acquire drug resistance. Microarray and functional studies of drug-resistant pretumorigenic cells indicate that the drug efflux pump P-glycoprotein is responsible for the MDR phenotype in this pretumorigenic cell model. [Cancer Res 2007;67(3):1130–7]
Glulisine Versus Human Regular Insulin in Combination With Glargine in Noncritically Ill Hospitalized Patients With Type 2 Diabetes
Authors: Christian Meyer, Anna Boron, Elena Plummer, Marina Voltchenok, Rosemarie Vedda
Journal: Diabetes Care (2010)

OBJECTIVE To compare the efficacy and safety of the rapid-acting insulin analog glulisine and regular insulin in hyperglycemic hospitalized patients. RESEARCH DESIGN AND METHODS A total of 180 hospitalized patients with type 2 diabetes received either glulisine (n = 88) or regular insulin (n = 92) before each meal in combination with insulin glargine at bedtime in a randomized double-blind fashion. All previous diabetes medications were discontinued if applicable. Doses of insulin were adjusted to obtain target blood glucose concentrations of &amp;lt;130 mg/dl before meals and at bedtime while avoiding hypoglycemia. RESULTS Overall mean blood glucose concentrations were ∼8 mg/dl lower in the glulisine group than in the regular insulin group (152.6 ± 66.6 vs. 160.4 ± 70.8 mg/dl; P &amp;lt; 0.0002). This improvement was wholly due to ∼22 mg/dl lower levels after 4 days of therapy (140 ± 55 vs. 162 ± 71 mg/dl; P &amp;lt; 0.0007); after day 4, this difference progressively increased such that mean blood glucose concentrations from day 7 onward were ∼31 mg/dl lower in the glulisine group. The mean daily incidence of hypoglycemia was slightly but not significantly lower in the glulisine than the regular insulin group (0.10 ± 0.02 vs. 0.14 ± 0.03 episode/day; P &amp;gt; 0.35). CONCLUSIONS In hospitalized type 2 diabetic patients, glulisine may provide better glycemic control than regular insulin, especially in those who have a prolonged length of stay.
Activated Protein C Resistance in Type I Diabetes
Authors: Gabriella Gruden, Carla Olivetti, Paolo Cavallo-Perin, Mario Bazzan, Stefania Stella, Giacomo Tamponi, Gianfranco Pagano
Journal: Diabetes Care (1997)

To compare activated protein C (aPC) sensitivity in 37 type I diabetic patients and 33 healthy control subjects.In this study, 37 type I diabetic patients and 33 healthy control subjects without personal or familial history of venous thrombosis and coagulation disorders, infections, intercurrent conditions, serum lupus anticoagulant, clinical cardiovascular complications, or drugs were examined.The aPC ratio (aPTT [activated partial thromboplastin time] with and without aPC) was significantly lower in the type I diabetic patients than in the control subjects (P = 0.005).These results suggest that the final steps of the protein C/S inhibiting system could be abnormal in type I diabetes.