tbuckley/cabot-search huggingface dataset:
Cigarette smoking accelerates progression of alcoholic chronic pancreatitis
Authors: P Maisonneuve
Journal: Gut (2005)

Smoking is a recognised risk factor for pancreatic cancer and has been associated with chronic pancreatitis and also with type II diabetes.The aim of this study was to investigate the effect of tobacco on the age of diagnosis of pancreatitis and progression of disease, as measured by the appearance of calcification and diabetes.We used data from a retrospective cohort of 934 patients with chronic alcoholic pancreatitis where information on smoking was available, who were diagnosed and followed in clinical centres in five countries.We compared age at diagnosis of pancreatitis in smokers versus non-smokers, and used the Cox proportional hazards model to evaluate the effects of tobacco on the development of calcification and diabetes, after adjustment for age, sex, centre, and alcohol consumption.The diagnosis of pancreatitis was made, on average, 4.7 years earlier in smokers than in non-smokers (p = 0.001). Tobacco smoking increased significantly the risk of pancreatic calcifications (hazard ratio (HR) 4.9 (95% confidence interval (CI) 2.3-10.5) for smokers v non-smokers) and to a lesser extent the risk of diabetes (HR 2.3 (95% CI 1.2-4.2)) during the course of pancreatitis.In this study, tobacco smoking was associated with earlier diagnosis of chronic alcoholic pancreatitis and with the appearance of calcifications and diabetes, independent of alcohol consumption.
The allergy‐associated chemokine receptors CCR3 and CCR5 can be inactivated by the modified chemokine NNY‐CCL11
Authors: J. Manns, S. Rieder, S. Escher, B. Eilers, W.‐G. Forssmann, J. Elsner, U. Forssmann
Journal: Allergy (2006)

Background: CC chemokine ligand 11 (CCL11) is the outstanding member of all described CC chemokine receptor 3 (CCR3) ligands and is shown to be selective for this receptor. However, it also activates CCR5 but only in the micromolar range. The in vivo activity of CCL11 is expected to be temporally restricted, as it is degraded by specific proteases such as the dipeptidyl‐peptidase IV (DP4), also termed CD26. Based on the approach to inactivate chemokine receptors in allergic disease models as has been demonstrated for DP4‐resistant n ‐nonanoyl (NNY)‐CCL14 and for amino‐oxypentane (AOP)‐CCL5, it is tempting to study similar compounds derived from CCL11. Methods: Synthesis of NNY‐CCL11 was performed and it was characterized for biological functions in human and mouse eosinophils as well as in cell lines stably transfected either with human CCR3 or CCR5. Resistance to DP4 treatment was also investigated. Results: The functional activities of NNY‐CCL11 mediated via CCR3 show an almost identical pattern to CCL11 with respect to intracellular calcium mobilization and CCR3 internalization. N‐terminal cleavage of CCL11 by preincubation with DP4 results in a reduced capacity to internalize CCR3, while preincubation of NNY‐CCL11 shows no influence. In contrast to CCL11, NNY‐CCL11 also activates CCR5 + cell lines and human monocytes in the nanomolar range, being about 100 times more potent than CCL11. Conclusions: n ‐Nonanoyl‐CCL11 represents a compound with dual activity restricted to CCR3 and CCR5. Because of its receptor‐inactivating capacity and stability against DP4 degradation, NNY‐CCL11 is a suitable tool for the decoding of the pathophysiological mechanisms of allergic diseases.
Spitz nevi: In vivo confocal microscopic features, dermatoscopic aspects, histopathologic correlates, and diagnostic significance
Authors: Giovanni Pellacani, Caterina Longo, Gerardo Ferrara, Anna Maria Cesinaro, Sara Bassoli, Pascale Guitera, Scott W. Menzies, Stefania Seidenari
Journal: Journal of the American Academy of Dermatology (2008)
Efaproxiral: Should We Hold Our Breath?
Authors: Penny K. Sneed
Journal: Journal of Clinical Oncology (2005)

Suh et al breathe a bit of new life into two long-standing endeavors with their report in this issue of a phase III study of whole-brain radiotherapy (WBRT) and efaproxiral (RSR13), a hemoglobin modifier meant to increase tissue oxygenation. For decades, radiation oncologists have sought to enhance tumor control and patient survival by addressing the problem of hypoxia and, separately, to improve results of WBRT by sensitization, dose escalation, or altered fractionation. In this large randomized trial, efaproxiral added to WBRT and oxygen breathing increased median survival time from 4.4 to 5.4 months (P .16) and the overall response rate from 38% to 46% (P .10). Larger gains were seen in the combined non–small-cell lung cancer (NSCLC) and breast cancer subset, for whom the median survival time improved from 4.4 to 6.0 months (P .07) and overall response rate improved from 41% to 54% (P .01).
Rapid prediction of rifampin susceptibility of Mycobacterium tuberculosis.
Authors: H Ohno, H Koga, T Kuroita, K Tomono, K Ogawa, K Yanagihara, Y Yamamoto, J Miyamoto, T Tashiro, S Kohno
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We evaluated the relationship between rifampin (RIF) susceptiblility and amino acid substitution in rpoB gene of Mycobacterium tuberculosis and the usefulness of rpoB gene sequencing in the rapid prediction of RIF susceptibility of M. tuberculosis in clinical specimens. A total of 76 genetic alterations in the 69 bp core region of rpoB gene were detected in 74 of 130 M. tuberculosis strains. Examination of the correlation between the minimum inhibitory concentrations (MICs) of RIF and amino acid substitutions in the 69 bp core region of rpoB gene revealed that all 43 strains containing amino acid substitution with Leu or Trp in codon 531 showed RIF-resistant phenotypes, with MICs > or = 64 microg/ml. In contrast, a variable level of RIF susceptibility was observed among strains containing amino acid substitutions in either codon 516 or codon 526. In the clinical study, we tested 26 sputum samples, two gastric lavages, and one synovial fluid sample obtained from patients with tuberculosis. The RIF susceptibility predicted by direct rpoB sequencing was satisfactorily compatible with the results of the RIF-susceptibility test and the MICs of RIF against isolated organisms. Our results suggest that rpoB gene sequencing is useful for the detection of M. tuberculosis in clinical samples as well as the rapid prediction of RIF susceptibility of these strains.
Impact of Brachytherapy on Local Recurrence Rates After Sublobar Resection: Results From ACOSOG Z4032 (Alliance), a Phase III Randomized Trial for High-Risk Operable Non–Small-Cell Lung Cancer
Authors: Hiran C. Fernando, Rodney J. Landreneau, Sumithra J. Mandrekar, Francis C. Nichols, Shauna L. Hillman, Dwight E. Heron, Bryan F. Meyers, Thomas A. DiPetrillo, David R. Jones, Sandra L. Starnes, Angelina D. Tan, Benedict D.T. Daly, Joe B. Putnam
Journal: Journal of Clinical Oncology (2014)

A major concern with sublobar resection (SR) for non-small-cell lung cancer (NSCLC) is high local recurrence (LR). Adjuvant brachytherapy may reduce LR This multicenter randomized trial compares SR to SR with brachytherapy (SRB).High-risk operable patients with NSCLC ≤ 3 cm were randomly assigned to SR or SRB. The primary end point was time to LR, where LR included recurrence at the staple line (local progression), in the primary tumor lobe away from the staple line, and in ipsilateral hilar nodes. The trial was designed to have a 90% power to detect a hazard ratio (HR) of 0.315 in favor of SRB, using a one-sided type I error rate of 0.05 with a sample size of 100 eligible patients in each arm.Two hundred twenty-four patients were randomly assigned; 222 patients were evaluable for intent-to-treat analysis. Median age was 71 years (range, 49 to 87 years). No differences were found in baseline characteristics. Median follow-up time was 4.38 years (range, 0.04 to 5.59 years). There was no difference in time to LR (HR, 1.01; 95% CI, 0.51 to 1.98; log-rank P = .98) or in the types of LR. Local progression occurred in only 17 (7.7%) of 222 patients. In patients with potentially compromised margins (margin < 1 cm, margin-to-tumor ratio < 1, positive staple line cytology, wedge resection, nodule size > 2.0 cm), SRB did not reduce LR, although trends favored the SRB arm. This was most marked in 14 patients with positive staple line cytology (HR, 0.22; P = .24). Three-year overall survival rates were similar for patients in the SR (71%) and SRB (71%) arms (P = .97).Brachytherapy did not reduce LR after SR. This finding may have been related to closer attention to parenchymal margins by surgeons participating in this study.
A Large Subset of Neutrophils Expressing Membrane Proteinase 3 Is a Risk Factor for Vasculitis and Rheumatoid Arthritis
Authors: VERONIQUE WITKO-SARSAT, PHILIPPE LESAVRE, SANDRA LOPEZ, GILLES BESSOU, CORINNE HIEBLOT, BERNARD PRUM, LAURE HÉLÈNE NOËL, LOÏC GUILLEVIN, PHILIPPE RAVAUD, ISABELLE SERMET-GAUDELUS, JOSE TIMSIT, JEAN-PIERRE GRÜNFELD, LISE HALBWACHS-MECARELLI
Journal: Journal of the American Society of Nephrology (1999)

Abstract. It has been shown previously that proteinase 3 (PR3), a neutrophil intracellular protease that is the main antigen of antineutrophil cytoplasm (ANCA) autoantibodies, is present on the plasma membrane of a subset of freshly isolated neutrophils. This study shows that the size of this subset of membrane PR3-positive (mPR3 + ) neutrophils is a stable feature of a given individual, most likely genetically controlled. It ranges from 0 to 100% of neutrophils and allows us to define a new polymorphism in the healthy population, with three discrete phenotypes corresponding respectively to less than 20% mPR3 + neutrophils (mPR3 low ) or to a mean percentage of 47% (mPR3 intermediate ) and 71.5% (mPR3 high ) mPR3 + neutrophils. The frequency of the mPR3 high phenotype was significantly increased in patients with ANCA-associated vasculitis (85% versus 55% in healthy subjects). The percentage of mPR3 + neutrophils was not affected by disease activity, relapses, or therapy, and did not reflect in vivo cell activation. In addition, mPR3 + phenotypes were normally distributed in cystic fibrosis patients, indicating that infection and/or inflammation per se do not lead to a high percentage of mPR3 + neutrophils. The frequency of the mPR3 high phenotype was not related to anti-PR3 autoimmunization, since it was increased in vasculitic patients regardless of the ANCA specificity (anti-PR3, anti-myeloperoxidase, or unknown). Interestingly, the frequency of the mPR3 high phenotype was also increased in patients with rheumatoid arthritis. It was normal in type I-diabetes, a T cell-dependent autoimmune disease. It is proposed here that a high proportion of membrane PR3-positive neutrophils could favor the occurrence or the progression of chronic inflammatory diseases.
GLI1 Modulates EMT in Pancreatic Cancer—Response
Authors: Simon Joost, Luciana L. Almada, Verena Rohnalter, Philipp S. Holz, Maite G. Fernandez-Barrena, Martin E. Fernandez-Zapico, Matthias Lauth
Journal: Cancer Research (2012)

In a recent publication ([1][1]), we showed that low levels of the GLI1 transcription factor sensitize pancreatic ductal adenocarcinoma (PDAC) cells to induce an epithelial-to-mesenchymal transition (EMT). Analysis of the mechanism identified E-cadherin (encoded by the CDH1 gene) as a direct target
Atypical Antipsychotics and Risk of Cerebrovascular Accidents
Authors: Nathan Herrmann, Muhammad Mamdani, Krista L Lanctôt
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Randomized controlled trials have suggested that at least one atypical antipsychotic may be associated with an increased risk of stroke in older people with dementia. This study examined the association between atypical antipsychotic use and stroke in the elderly. METHOD: The authors conducted a retrospective population-based cohort study of patients over the age of 66 by linking administrative health care databases. Three cohorts—users of typical antipsychotics, risperidone, and olanzapine—were identified and compared. RESULTS: Subjects treated with typical antipsychotics (N=1,015) were compared with those given risperidone (N=6,964) and olanzapine (N=3,421). Model-based estimates adjusted for covariates hypothesized to be associated with stroke risk revealed relative risk estimates of 1.1 (95% CI=0.5–2.3) for olanzapine and 1.4 (95% CI=0.7–2.8) for risperidone. CONCLUSIONS: Olanzapine and risperidone use were not associated with a statistically significant increased risk of stroke compared with typical antipsychotic use.
Delta Virus Infection and Severe Hepatitis
Authors: STEPHEN C. HADLER
Journal: Annals of Internal Medicine (1984)

Over a 3-year period, 149 Yucpa Indians in Venezuela developed hepatitis; 34 persons died and at least 22 developed chronic hepatitis. Children and young adults were primarily affected, especially males. Serologic testing showed that hepatitis B virus infection was highly endemic in this population, but also that 65% of patients had hepatitis B virus surface antigen (HBsAg) during or after illness. Most patients had evidence of delta-agent superinfection; 86% of HBsAg-positive patients had delta antibody, and delta antigen was found in specimens taken during autopsies on 7 of 9 patients. Serologic data suggested that most infections were due to delta superinfection of hepatitis B carriers, and that more than 60% of these infections progressed to chronic disease. Delta agent infection, and particularly delta superinfection of hepatitis B carriers, appears to be an ominous occurrence that may develop in populations among whom hepatitis B virus infection is endemic, and who have no other risk factor for delta infection.
HIV-1 Drug Resistance Profiles in Children and Adults With Viral Load of &amp;lt;50 Copies/mL Receiving Combination Therapy
Authors: Monika Hermankova
Journal: JAMA (2001)

ContextThe continued release of human immunodeficiency virus type 1 (HIV-1) into plasma at very low levels during highly active antiretroviral therapy (HAART) can be detected using specialized techniques, but the nature and significance of this low-level viremia, especially as related to acquisition of drug resistance mutations, are unclear.ObjectiveTo determine genetic resistance profiles of low-level plasma HIV-1 in patients with prolonged viral suppression (<50 copies/mL of plasma HIV-1 RNA) while receiving HAART.Design and SettingCross-sectional study conducted at a US academic hospital from November 1999 to February 2001 using a novel method for amplification of low levels of viral genomes in plasma.PatientsEighteen HIV-1–infected patients (7 children and 11 adults), enrolled in a longitudinal study of HIV-1 reservoirs, who had suppression of viral replication while receiving protease inhibitor–containing combination therapy. Two patients (1 adult and 1 child) with less optimal suppression of viral replication were included to assess virus predominating when plasma HIV-1 RNA levels are low but detectable (<1000 copies/mL). Follow-up analyses were conducted in 3 patients.Main Outcome MeasureDetection of drug resistance mutations in clones amplified from low-level plasma virus.ResultsViral sequences were amplified from 8 of the 18 patients with simultaneous plasma HIV-1 measurements of less than 50 copies/mL and from 2 patients with 231 and 50 copies/mL. Clones from 3 treatment-naive patients with less than 50 copies/mL of plasma HIV-1 RNA showed continued release, for as long as 42 months, of wild-type drug-sensitive virus. The 7 patients with prior nonsuppressive therapy, with viral loads below 50 copies/mL and during "blips" to 231 and 64 copies/mL, had only resistance mutations consistent with pre-HAART therapy (although reverse transcriptase inhibitor mutations may have continued to occur). New HAART-related mutations were seen in a control patient with prior viral load levels of about 400 to 1000 copies/mL. For phylogenetic analysis, sequences were available for both resting CD4+ T cells and plasma HIV for 7 of 10 patients and showed patient-specific clustering of sequences and a close relationship between virus in the plasma and the latent reservoir.ConclusionsBased on the samples that could be amplified, low-level viremia in children and adults receiving HAART with prolonged suppression of viremia to less than 50 copies/mL of HIV-1 RNA may result primarily from archival, pre-HAART virus, reflecting earlier treatment conditions, and does not appear to require development of new, HAART-selected mutations reflecting partial resistance to therapy. Low-level viremia below 50 copies/mL may represent less of a concern regarding impending drug failure of current HAART regimens. However, the archival drug-resistant virus may be relevant regarding future treatment strategies.
Improved Survival with HPV among African Americans with Oropharyngeal Cancer
Authors: Maria J. Worsham, Josena K. Stephen, Kang Mei Chen, Meredith Mahan, Vanessa Schweitzer, Shaleta Havard, George Divine
Journal: Clinical Cancer Research (2013)

Abstract Purpose: A major limitation of studies reporting a lower prevalence rate of human papilloma virus (HPV) in African American patients with oropharyngeal squamous cell cancer (OPSCC) than Caucasian Americans, with corresponding worse outcomes, was adequate representation of HPV-positive African American patients. This study examined survival outcomes in HPV-positive and HPV-negative African Americans with OPSCC. Experimental Design: The study cohort of 121 patients with primary OPSCC had 42% African Americans. Variables of interest included age, race, gender, HPV status, stage, marital status, smoking, treatment, and date of diagnosis. Results: Caucasian Americans are more likely to be HPV positive (OR = 3.28; P = 0.035), as are younger age (age &amp;lt; 50 OR = 7.14; P = 0.023 compared with age &amp;gt; 65) or being married (OR = 3.44; P = 0.016). HPV positivity and being unmarried were associated with being late stage (OR = 3.10; P = 0.047 and OR = 3.23; P = 0.038, respectively). HPV-negative patients had 2.7 times the risk of death as HPV-positive patients (P = 0.004). Overall, the HPV-race groups differed (log-rank P &amp;lt; 0.001), with significantly worse survival for HPV-negative African Americans versus (i) HPV-positive African Americans (HR = 3.44; P = 0.0012); (ii) HPV-positive Caucasian Americans (HR = 3.11; P = &amp;lt; 0.049); and (iii) HPV-negative Caucasian Americans (HR = 2.21; P = 0.049). Conclusions: HPV has a substantial impact on overall survival in African American patients with OPSCC. Among African American patients with OPSCC, HPV-positive patients had better survival than HPV negative. HPV-negative African Americans also did worse than both HPV-positive Caucasian Americans and HPV-negative Caucasian Americans. This study adds to the mounting evidence of HPV as a racially linked sexual behavior life style risk factor impacting survival outcomes for both African American and Caucasian American patients with OPSCC. Clin Cancer Res; 19(9); 2486–92. ©2013 AACR.
Myocardial digoxin uptake in pressure overload right ventricular hypertrophy
Authors: B. E. HOPKINS, B. L. LLOYD, R. R. TAYLOR
Journal: Cardiovascular Research (1974)

Journal Article Myocardial digoxin uptake in pressure overload right ventricular hypertrophy Get access BARRY E. HOPKINS, BARRY E. HOPKINS From the Department of Medicine, University of Western Australia; The Research Centre and Cardiology Unit of Royal Perth Hospital, Perth, Western Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar BRIAN L. LLOYD, BRIAN L. LLOYD From the Department of Medicine, University of Western Australia; The Research Centre and Cardiology Unit of Royal Perth Hospital, Perth, Western Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar ROGER R. TAYLOR ROGER R. TAYLOR From the Department of Medicine, University of Western Australia; The Research Centre and Cardiology Unit of Royal Perth Hospital, Perth, Western Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 8, Issue 5, September 1974, Pages 701–706, https://doi.org/10.1093/cvr/8.5.701 Published: 01 September 1974
Different patterns of postprandial lipoprotein metabolism in normal, type IIa, type III, and type IV hyperlipoproteinemic individuals. Effects of treatment with cholestyramine and gemfibrozil.
Authors: M S Weintraub, S Eisenberg, J L Breslow
Journal: Journal of Clinical Investigation (1987)

To study exogenous fat metabolism, we used the vitamin A-fat loading test, which specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). Postprandial RP concentrations were followed in total plasma, and chylomicron (Sf greater than 1,000) and nonchylomicron (Sf less than 1,000) fractions. In normal subjects postprandial lipoproteins were present for more than 14 h, and chylomicron levels correlated inversely with lipoprotein lipase activity and fasting high density lipoprotein (HDL) cholesterol levels and nonchylomicron levels correlated inversely with hepatic triglyceride lipase activity. The main abnormality in type IV patients was a 5.6-fold increase in the chylomicron fraction, whereas in type III patients it was a 6.4-fold increase in nonchylomicrons. Type IIa patients had abnormally low chylomicron fractions. In type IV patients gemfibrozil decreased, whereas in type IIa patients cholestyramine increased the chylomicron fraction 66 and 88%, respectively. This study demonstrates an unexpectedly large magnitude and long duration of postprandial lipemia in normal subjects and patients. These particles are potentially atherogenic, and their role in human atherosclerosis warrants further study.
Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions
Authors: Stewart MacArthur, Xiao-Yong Li, Jingyi Li, James B Brown, Hou Cheng Chu, Lucy Zeng, Brandi P Grondona, Aaron Hechmer, Lisa Simirenko, Soile VE Keränen, David W Knowles, Mark Stapleton, Peter Bickel, Mark D Biggin, Michael B Eisen
Journal: Genome biology (2009)

Abstract Background We previously established that six sequence-specific transcription factors that initiate anterior/posterior patterning in Drosophila bind to overlapping sets of thousands of genomic regions in blastoderm embryos. While regions bound at high levels include known and probable functional targets, more poorly bound regions are preferentially associated with housekeeping genes and/or genes not transcribed in the blastoderm, and are frequently found in protein coding sequences or in less conserved non-coding DNA, suggesting that many are likely non-functional. Results Here we show that an additional 15 transcription factors that regulate other aspects of embryo patterning show a similar quantitative continuum of function and binding to thousands of genomic regions in vivo . Collectively, the 21 regulators show a surprisingly high overlap in the regions they bind given that they belong to 11 DNA binding domain families, specify distinct developmental fates, and can act via different cis -regulatory modules. We demonstrate, however, that quantitative differences in relative levels of binding to shared targets correlate with the known biological and transcriptional regulatory specificities of these factors. Conclusions It is likely that the overlap in binding of biochemically and functionally unrelated transcription factors arises from the high concentrations of these proteins in nuclei, which, coupled with their broad DNA binding specificities, directs them to regions of open chromatin. We suggest that most animal transcription factors will be found to show a similar broad overlapping pattern of binding in vivo , with specificity achieved by modulating the amount, rather than the identity, of bound factor.