tbuckley/cabot-search huggingface dataset:
Molecular Damage in the Bronchial Epithelium of Current and Former Smokers
Authors: I. I. Wistuba, A. K. Virmani, A. F. Gazdar, S. Lam, J. LeRiche, C. Behrens, K. M. Fong, J. M. Samet, S. Srivastava, J. D. Minna
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Most lung cancers are attributed to smoking. These cancers have been associated with multiple genetic alterations and with the presence of preneoplastic bronchial lesions. In view of such associations, we evaluated the status of specific chromosomal loci in histologically normal and abnormal bronchial biopsy specimens from current and former smokers and specimens from nonsmokers. Methods: Multiple biopsy specimens were obtained from 18 current smokers, 24 former smokers, and 21 nonsmokers. Polymerase chain reaction-based assays involving 15 polymorphic microsatellite DNA markers were used to examine eight chromosomal regions for genetic changes (loss of heterozygosity [LOH] and microsatellite alterations). Results: LOH and microsatellite alterations were observed in biopsy specimens from both current and former smokers, but no statistically significant differences were observed between the two groups. Among individuals with a history of smoking, 86% demonstrated LOH in one or more biopsy specimens, and 24% showed LOH in all biopsy specimens. About half of the histologically normal specimens from smokers showed LOH, but the frequency of LOH and the severity of histologic change did not correspond until the carcinoma in situ stage. A subset of biopsy specimens from smokers that exhibited either normal or preneoplastic histology showed LOH at multiple chromosomal sites, a phenomenon frequently observed in carcinoma in situ and invasive cancer. LOH on chromosomes 3p and 9p was more frequent than LOH on chromosomes 5q, 17p (17p13; TP53 gene), and 13q (13q14; retinoblastoma gene). Microsatellite alterations were detected in 64% of the smokers. No genetic alterations were detected in nonsmokers. Conclusions: Genetic changes similar to those found in lung cancers can be detected in the nonmalignant bronchial epithelium of current and former smokers and may persist for many years after smoking cessation.
Intramural Hematoma of the Aorta
Authors: Yskert von Kodolitsch, Susanne K. Csösz, Dietmar H. Koschyk, Ilka Schalwat, Roger Loose, Matthias Karck, Christoph Dieckmann, Rossella Fattori, Axel Haverich, Jürgen Berger, Thomas Meinertz, Christoph A. Nienaber
Journal: Circulation (2003)

Aortic intramural hematoma (IMH) is a variant of overt aortic dissection. The predictors of progression of IMH to dissection and rupture are still unknown, and strategies for management are not established.A multicenter study was conducted comprising 66 patients with IMH and hospital admission <or=48 hours after onset of initial symptoms. Among these, progression to aortic dissection or rupture occurred in 30 (45%) and death occurred in 13 (20%) patients within 30 days. Late progression was noted in 14 (21%) and death in 11 (17%) patients, yielding a 1-, 2-, and 5-year survival of 76%, 73%, and 43%, respectively. In a set of 9 variables, multivariate analysis identified IMH location in the ascending aorta (type A; P=0.02) and moderately ectatic aortic diameters (49+/-13 mm with progression versus 57+/-16 mm without progression; P=0.03) as independent predictors of early progression. In type A IMH, early mortality was 8% with swift surgery versus 55% without surgery (P=0.004). The risk of late progression of IMH was independently associated with age at index diagnosis (P=0.01) and absence of beta-blocker therapy during follow-up (P=0.03). Kaplan-Meier analysis confirmed improved 1-year survival of IMH with beta-blocker therapy (95% versus 67% without beta-blockers; P=0.004).Regardless of aortic diameter, IMH of the ascending aorta (type A) is at high risk for early progression, and, thus, undelayed surgical repair should be performed. Moreover, oral beta-blocker therapy may improve long-term prognosis of IMH independent of anatomical location.
Associations between birth weight, early childhood weight gain and adult lung function
Authors: R J Hancox, R Poulton, J M Greene, C R McLachlan, M S Pearce, M R Sears
Journal: Thorax (2008)

<h3>Background:</h3> Low birth weight is associated with lower values for spirometry in adults but it is not known if birth weight influences other measures of pulmonary function. It is also unclear whether postnatal growth affects adult lung function. The associations between birth weight, postnatal growth and adult lung function were assessed in an unselected birth cohort of 1037 children. <h3>Methods:</h3> Birth weight, weight gain between birth and age 3 years, and lung function at age 32 years were measured. Analyses were adjusted for adult height and sex and further adjusted for multiple other potential confounding factors. <h3>Results:</h3> Birth weight was positively correlated with spirometric (forced expiratory volume in 1 s and forced vital capacity) and plethysmographic (total lung capacity and functional residual capacity) lung function and with lung diffusing capacity. These associations persisted after adjustment for confounding factors including adult weight, exposure to cigarette smoke in utero and during childhood, personal smoking, socioeconomic status, asthma and gestational age. Weight gain between birth and age 3 years was also positively associated with lung diffusing capacity, and with higher values of lung volumes in men after adjustment for covariates. Neither birth weight nor postnatal weight gain was associated with airflow obstruction. <h3>Conclusions:</h3> Low birth weight and lower weight gain in early childhood are associated with modest reductions in adult lung function across a broad range of measures of lung volumes and with lower diffusing capacity. These findings are independent of a number of potential confounding factors and support the hypothesis that fetal and infant growth is a determinant of adult lung function.
Primary tracheo-bronchial amyloidosis studied with 64-slice MDCT (2D and 3D reconstructions)
Authors: F. Boccuzzi, M. Busso, L. Cardinale, C. Fava
Journal: Thorax (2010)

Images in ThoraxPrimary tracheo-bronchial amyloidosis studied with 64-slice MDCT (2D and 3D reconstructions)A 50-year-old Caucasian man was presented to the emergency department with cough and progressive dyspnoea.Plain chest x-ray showed multiple pseudo-nodular parenchymal opacities, partly confluent and calcified, prominent in the middle-basal lung fields (figure 1A).Volumetric high-resolution computed tomography (HRCT) confirmed multiple bilateral parenchymal nodules with lobulated margins and extensive calcifications due to diffuse bronchiectasis with thickened and calcified walls (figure 1BeC).Airways involvement was evident, characterised by submucosal deposits and lumen distortion mainly in the trachea, without sparing of the posterior membranous portion, and main and segmental bronchi (figure 2).Biopsy specimen from bronchoscopy was striking for amyloid (figure 3), therefore the evidence pointed towards a diagnosis of primary tracheo-bronchial amyloidosis.
Lower Body X Irradiation and 3-Methylcholanthrene Administration in Breast-Tumor Induction in the Wistar Rat&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Harry Shay, Margot Gruenstein, Claire J. Shellabarger, Woodrow B. Kessler, L. L. Ashburn
Journal: JNCI Journal of the National Cancer Institute (1962)

X irradiation (400 r) to the caudal half of the body of Wistar rats was weakly tumorigenic and even weaker as a carcinogen. Tumors appeared almost entirely in area of X-ray exposure. Appearance time of the 1 X-ray-induced adenocarcinoma and the average for the 5 fibroadenomas were long compared with mean appearance time (MAT) of first adenocarcinoma induced by 3-methylcholanthrene (3-MCA). Partial body X ray plus 3-MCA decreased MAT significantly. Partial body X irradiation and the 2 mg dose of 3-MCA 6 days a week shifted tumor frequency in favor of X-ray-exposed area. The 5 mg dose of 3-MCA alone so equalized distribution of tumors between thoracocervical (TC) and abdominoinguinal areas (AI) that added X-ray exposure of AI area produced no further significant shift. Breast-tumor induction by X ray was almost entirely a local tissue action. However, action of X ray on 3-MCA breast-cancer induction may also have carried a systemic effect. X ray (400 r) delivered to the caudal half of the body affected ovari an weight and histology. These changes did not abolish the functional capacity of ovaries to supply promoting agents important for induction of breast cancer by 3-MCA. Increasing daily dose of 3-MCA from 2 to 5 mg hastened appearance time of all breast cancers, increased tumors per tumor-bearing animal, and tended to equalize distribution and induction time of cancers in TC and AI areas. Increasing daily dose of 3-MCA enhanced its promoting action, its high efficiency as an initiator having been demonstrated with the 2 mg dose.
Transforming growth factor ? and liver regeneration: The stage may be set, but what's the script?
Authors: B H Davis, A Chen
Journal: Hepatology (1996)

lipocytes (Ito or stellate cells) from normal and regener-San Diego, CA ating liver.In normal liver, TGF-b1 and -b2 levels were relatively high in sinusoidal endothelial cells and Kupf-REFERENCES fer cells.After partial hepatectomy, an early peak of TGF-b2 and -b3 was present in all four cell types, fol-1.Houglum K, Filip M, Witztum JL, Chojkier M. Malondialdehyde lowed by a sustained increase in messenger RNA and 4-hydroxynonenal protein adducts in plasma and liver of (mRNA) for TGF-b1, -b2, and -b3 primarily in the hepatorats with iron overload.
Unexplained Vomiting: A Diagnostic Challenge
Authors: JUAN-R. MALAGELADA
Journal: Annals of Internal Medicine (1984)

When vomiting is not related to preventing the entry of physically or chemically unsuitable substances into the absorbing gut, it may be regarded as pathologic. The commonest causes of chronic vomiting are structural lesions affecting the mucosa of the upper gastrointestinal tract (often with luminal obstruction) and psychogenic disorders. Diseases affecting extrinsic and intrinsic neural control of gut motility and visceral smooth muscle may also cause unexplained vomiting. A stratified management approach to patients with vomiting is suggested. The first assessment is aimed at exclusion of mucosal lesions of the upper gut and systemic or psychiatric disease that may affect it. Second is a therapeutic trial, usually with a prokinetic agent. The final phase, reserved for recalcitrant undiagnosed patients, is evaluation at special centers with gastric emptying studies, gastrointestinal manometry, other electrophysiologic studies, and, in a few patients, laparotomy with examination of full-thickness biopsy specimens of the small intestine.
Modeling antibiotic and cytotoxic effects of the dimeric isoquinoline IQ-143 on metabolism and its regulation in Staphylococcus aureus, Staphylococcus epidermidis and human cells
Authors: Alexander Cecil, Carina Rikanović, Knut Ohlsen, Chunguang Liang, Jörg Bernhardt, Tobias A Oelschlaeger, Tanja Gulder, Gerhard Bringmann, Ulrike Holzgrabe, Matthias Unger, Thomas Dandekar
Journal: Genome biology (2011)

Xenobiotics represent an environmental stress and as such are a source for antibiotics, including the isoquinoline (IQ) compound IQ-143. Here, we demonstrate the utility of complementary analysis of both host and pathogen datasets in assessing bacterial adaptation to IQ-143, a synthetic analog of the novel type N,C-coupled naphthyl-isoquinoline alkaloid ancisheynine. Metabolite measurements, gene expression data and functional assays were combined with metabolic modeling to assess the effects of IQ-143 on Staphylococcus aureus, Staphylococcus epidermidis and human cell lines, as a potential paradigm for novel antibiotics. Genome annotation and PCR validation identified novel enzymes in the primary metabolism of staphylococci. Gene expression response analysis and metabolic modeling demonstrated the adaptation of enzymes to IQ-143, including those not affected by significant gene expression changes. At lower concentrations, IQ-143 was bacteriostatic, and at higher concentrations bactericidal, while the analysis suggested that the mode of action was a direct interference in nucleotide and energy metabolism. Experiments in human cell lines supported the conclusions from pathway modeling and found that IQ-143 had low cytotoxicity. The data suggest that IQ-143 is a promising lead compound for antibiotic therapy against staphylococci. The combination of gene expression and metabolite analyses with in silico modeling of metabolite pathways allowed us to study metabolic adaptations in detail and can be used for the evaluation of metabolic effects of other xenobiotics.
n of 1 trials comparing a non-steroidal anti-inflammatory drug with paracetamol in osteoarthritis
Authors: L March, L Irwig, J Schwarz, J Simpson, C Chock, P Brooks
Journal: BMJ (1994)

<b>OBJECTIVE:</b> To evaluate the efficacy of paracetamol and a non-steroidal anti-inflammatory drug for symptom relief in osteoarthritis. <b>DESIGN:</b> Double blind, randomised, controlled trials in individual patients (n of 1 trials). Three treatment cycles with two weeks9 each of paracetamol (1 g twice daily) and diclofenac (50 mg twice daily) prepared in identical gelatin capsules. <b>SETTING:</b> General practices in metropolitan Sydney, Australia. <b>SUBJECTS:</b> 25 patients (median age 64 years) with pain of osteoarthritis (median duration of disease eight years) considered by their general practitioners to require regular treatment. 20 were already taking non-steroidal anti-inflammatory drugs. <b>MAIN OUTCOME MEASURES:</b> Diary of pain and stiffness, function, and side effects. <b>RESULTS:</b> 15 patients completed the study, five withdrew early but had made a therapeutic decision, and five dropped out very early. Results from 20 patients were analysed. Several patterns of response evolved. Eight of the 20 patients found no clear difference, symptoms being adequately controlled by paracetamol; five indicated a clear preference for the non-steroidal anti-inflammatory drug; two showed control of symptoms after their initial two weeks of the non-steroidal anti-inflammatory drug which continued throughout subsequent treatment changes; in five the non-steroidal anti-inflammatory drug may have been better but neither agent gave satisfactory control. After three months nine of the 20 patients had adequate symptom control with paracetamol alone. <b>CONCLUSIONS:</b> Of 1 studies--that is, randomised trials in individual patients--are clinically useful in deciding treatment in heterogeneous conditions which require long term symptomatic relief. In osteoarthritis many patients currently receiving or being considered for non-steroidal anti-inflammatory drugs may achieve adequate control with paracetamol.
American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer
Authors: Christopher G. Azzoli, Sherman Baker, Sarah Temin, William Pao, Timothy Aliff, Julie Brahmer, David H. Johnson, Janessa L. Laskin, Gregory Masters, Daniel Milton, Luke Nordquist, David G. Pfister, Steven Piantadosi, Joan H. Schiller, Reily Smith, Thomas J. Smith, John R. Strawn, David Trent, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2009)

The purpose of this article is to provide updated recommendations for the treatment of patients with stage IV non-small-cell lung cancer. A literature search identified relevant randomized trials published since 2002. The scope of the guideline was narrowed to chemotherapy and biologic therapy. An Update Committee reviewed the literature and made updated recommendations. One hundred sixty-two publications met the inclusion criteria. Recommendations were based on treatment strategies that improve overall survival. Treatments that improve only progression-free survival prompted scrutiny of toxicity and quality of life. For first-line therapy in patients with performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For patients with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with carboplatin-paclitaxel, except for patients with certain clinical characteristics. Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs. Data are insufficient to recommend routine use of molecular markers to select chemotherapy.
Potent Protection against Aflatoxin-Induced Tumorigenesis through Induction of Nrf2-Regulated Pathways by the Triterpenoid 1-[2-Cyano-3-,12-Dioxooleana-1,9(11)-Dien-28-Oyl]Imidazole
Authors: Melinda S. Yates, Mi-Kyoung Kwak, Patricia A. Egner, John D. Groopman, Sridevi Bodreddigari, Thomas R. Sutter, Karen J. Baumgartner, B.D. Roebuck, Karen T. Liby, Mark M. Yore, Tadashi Honda, Gordon W. Gribble, Michael B. Sporn, Thomas W. Kensler
Journal: Cancer Research (2006)

Abstract Synthetic triterpenoid analogues of oleanolic acid are potent inducers of the phase 2 response as well as inhibitors of inflammation. We show that the triterpenoid, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), is a highly potent chemopreventive agent that inhibits aflatoxin-induced tumorigenesis in rat liver. The chemopreventive potency of CDDO-Im was evaluated by measuring inhibition of formation of putative preneoplastic lesions (glutathione S-transferase P positive foci) in the liver of rats exposed to aflatoxin B1. CDDO-Im produces an 85% reduction in the hepatic focal burden of preneoplastic lesions at 1 μmol/kg body weight and a &amp;gt;99% reduction at 100 μmol/kg body weight. CDDO-Im treatment reduces levels of aflatoxin-DNA adducts by ∼40% to 90% over the range of 1 to 100 μmol/kg body weight. Additionally, changes in mRNA levels of genes involved in aflatoxin metabolism were measured in rat liver following a single dose of CDDO-Im. GSTA2, GSTA5, AFAR, and EPHX1 transcripts are elevated 6 hours following a 1 μmol/kg body weight dose of CDDO-Im. Microarray analysis using wild-type and Nrf2 knockout mice confirms that many phase 2 and antioxidant genes are induced in an Nrf2-dependent manner in mouse liver following treatment with CDDO-Im. Thus, low-micromole doses of CDDO-Im induce cytoprotective genes, inhibit DNA adduct formation, and dramatically block hepatic tumorigenesis. As a point of reference, oltipraz, an established modulator of aflatoxin metabolism in humans, is 100-fold weaker than CDDO-Im in this rat antitumorigenesis model. The unparalleled potency of CDDO-Im in vivo highlights the chemopreventive promise of targeting Nrf2 pathways with triterpenoids. (Cancer Res 2006; 66(4): 2488-94)
Predictive value of perioperative gastric acid tests.
Authors: J M Hood, E F Spencer, K D MacRae, T Kennedy
Journal: Gut (1976)

Preoperative acid studies and early postoperative insulin tests in 275 patients undergoing various forms of vagotomy have been related to recurrent ulceration. Follow-up time has been from two to nine years, mean 4-3 years. Recurrence is directly related to basal acidity in both tests but is not related to stimulated acid levels preoperatively. In the insulin tests higher levels of acidity after insulin are associated with a higher incidence of recurrence. When positive, Hollander9s and multiple criteria are both associated with a higher recurrence rate.
Incidence and Prevalence of Unrecognized Myocardial Infarction in People With Diabetes
Authors: Michael R. MacDonald, Mark C. Petrie, Philip D. Home, Michel Komajda, Nigel P. Jones, Henning Beck-Nielsen, Ramon Gomis, Markolf Hanefeld, Stuart J. Pocock, Paula S. Curtis, John J.V. McMurray
Journal: Diabetes Care (2011)

To examine the prevalence and incidence of unrecognized myocardial infarction in a contemporary population with type 2 diabetes.We performed a retrospective analysis of the electrocardiograms (ECGs) recorded at baseline and after 2 years for the first 1,004 type 2 diabetic individuals to be randomized in the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) study.ECGs suitable for analysis were obtained from 669 participants. The prevalence of unrecognized Q-wave myocardial infarction at baseline was 1.9% (n = 13). The incidence of unrecognized Q-wave myocardial infarction at the end of 2 years of follow-up was 1.5/1,000-person-years (n = 2). One-third (13 of 39) of prevalent and one-quarter (2 of 8) of incident myocardial infarctions were unrecognized.Although the prevalence and incidence of myocardial infarction was low, unrecognized Q-wave myocardial infarctions made up a substantial proportion of all events.
Effects of glucose on receptor-mediated phosphoinositide hydrolysis and second messenger generation in rat glomerular mesangial cells.
Authors: N J Guzman, P Kurian, V J Andaloro, C C Tisher, F T Crews
Journal: Journal of the American Society of Nephrology (1991)

The phosphoinositide system plays a critical role in mesangial cell contraction. myo-Inositol depletion occurs in glomeruli from diabetic animals and may result in mesangial cell dysfunction. The hypothesis that mesangial cell exposure to high concentrations of glucose could lead to abnormalities in phosphoinositide metabolism and receptor-mediated inositol phosphate release was tested. When compared with controls (5 mM glucose), inositol phosphate release in mesangial cells exposed to 28 mM glucose was decreased by 27% after maximal stimulation with angiotensin II, by 41% after arginine vasopressin, and by 63% after the thromboxane A2 analog, U46619. Increasing the concentration of glucose to 50 mM caused a further reduction (from 27 to 54%) in maximal angiotensin II stimulation of inositol phosphate release. High glucose decreased incorporation of myo-inositol into phospholipids but did not change phosphoinositide mass. High glucose also resulted in increased de novo synthesis of diacylglycerol which was associated with membrane translocation of protein kinase C. myo-inositol supplementation prevented the reduction in phosphoinositide hydrolysis whereas sorbinil did not. It was concluded that high concentrations of glucose cause abnormalities in myo-inositol metabolism in mesangial cells which lead to reduced receptor-mediated phosphoinositide hydrolysis. These abnormalities appear to be related to desensitization of receptor-mediated phosphoinositide responses due to negative feedback by protein kinase C which becomes activated as a result of enhanced de novo diacylglycerol formation from glucose. These changes are unrelated to the polyol pathway and can be prevented by myo-inositol supplementation.