tbuckley/cabot-search huggingface dataset:
Reply to V.R. Bhatt et al and M.C. Chamberlain
Authors: James W. Welsh, Susan L. McGovern, Jeffrey S. Wefel, Ritsuko Komaki, Paul D. Brown, Hendrick E. Soh
Journal: Journal of Clinical Oncology (2013)

suggests that, at present, there are no compelling data to commend coadministering a systemic agent with radiotherapy for the treatment of BM.However, erlotinib may be useful in the context of asymptomatic BM in patients with NSCLC who are naive to EGFR inhibitors and have mutated EGFR, who nonetheless require close neurologic follow-up.
Physiological upper limits of left ventricular dimensions in highly trained junior tennis players
Authors: Sandeep Basavarajaiah, Mathew Wilson, Reza Naghavi, Gregory Whyte, Mike Turner, Sanjay Sharma
Journal: British Journal of Sports Medicine (2007)

Background: The differentiation between physiological cardiac enlargement and cardiomyopathy is crucial, considering that most young non-traumatic deaths in sport are due to cardiomyopathy. Currently, there are few data relating to cardiac dimensions in junior elite tennis players. The aim of this study was to define the upper limits of left ventricular dimensions in a large cohort of national adolescent tennis players. Methods: Between 1996 and 2003, 259 adolescent tennis players (152 males), mean (SD) age 14.8 (1.4) years (range 13–19) and 86 healthy age, gender and body surface matched sedentary controls underwent 12-lead ECG and 2D-transthoracic echocardiography. Results: Inter-ventricular septal end diastolic dimension (IVSd), left ventricular end diastolic dimension (LVEDd) and left ventricular end diastolic posterior wall dimension (LVPWd) in tennis players were significantly higher than in controls (8.9 mm vs 8.3 mm p&lt;0.001, 48.9 mm vs 47.9 mm p&lt;0.05 and 9 mm vs 8.3 mm p&lt;0.001 respectively), however in absolute terms, the difference did not exceed 7%. None of the tennis players had a wall thickness exceeding 12 mm or a left ventricular cavity size exceeding 60 mm. Conclusions: Tennis players exhibit modest increases in cardiac dimensions, which do not resemble those seen in individuals with cardiomyopathy affecting the left ventricle.
P251 Prevalence and treatment outcome of Obstructive Sleep Apnoea (OSA) diagnosed following preoperative screening compared with GP or other clinician referral
Authors: A Dwarakanath, V Palissery, MW Elliott
Journal: Thorax (2013)

<h3>Introduction</h3> OSA is very prevalent and has potential implications perioperatively. Preoperative screening may identify high risk patients and treatment with CPAP may reduce perioperative complications, though this is unproven. We evaluated the treatment outcome and long term compliance with CPAP in patients diagnosed through preoperative screening and compared it with patients diagnosed with OSAS following GP or other clinician referral. <h3>Method</h3> Over 2 years (October 2009–2011) 1412 patients (males-62%) had sleep studies (oximetry or respiratory variable). 44% were referred from the preassessment clinic following screening for possible OSA. The prevalence of sleep disordered breathing, the Epworth Sleepiness Score (ESS) and among those referred for a CPAP trial the outcome, long-term compliance and average use per night were compared between preassessment and clinician referred patients. <h3>Results</h3> The prevalence of OSA was 62% and 58% in the clinician referred and preassessment patients respectively. There was a significant difference in age (61 +/-16 v/s 55 +/-13, P = &lt;0.0001) and ESS (11 +/-6 v/s 8 +/-5, P = &lt;0.0001) between the two groups. Clinician referred patients were more likely to be commenced on CPAP (P = &lt;0.0001, OR- 2.79). Preassessment patients with mild OSA who were prescribed CPAP were more likely to fail the CPAP trial (P = 0.01, OR- 3.02) and were less likely to continue CPAP treatment after one year (P = 0.02, OR-2.1). No difference was seen between the groups in patients with moderate or severe OSA. There was a significant difference in the median CPAP usage, 5.5 hours v/s 4 hours (Mann Whitney, P = 0.0053, figure-1). Both groups reported a significant improvement in ESS with CPAP (Δ ESS-5 and Δ ESS-4, P = &lt;0.0001) between the clinician referred and preassessment patients respectively. <h3>Conclusions</h3> The prevalence of OSA was similar in patients referred following preoperative screening or from another clinician, but preassessment patients were younger and less symptomatic. There was no difference in short or long term CPAP use in patients with moderate or severe OSA, but preassessment patients with mild OSA were less likely to use CPAP in the short or longer term. Opportunistic screening of patients awaiting surgery is worthwhile, independently of any effect of CPAP upon surgical outcomes.
Nitric Oxide Attenuates Signal Transduction
Authors: Hong Li, Sergey Brodsky, Mary Basco, Victor Romanov, Dino A. De Angelis, Michael S. Goligorsky
Journal: Circulation Research (2001)

Abstract —Caveolae harbor different serpentine receptors, intracellular components of signaling cascades, and certain enzymes, including endothelial nitric oxide synthase (eNOS). The regulation of eNOS activity by Ca 2+ /calmodulin and caveolin has been described. We have previously demonstrated that nitric oxide (NO) can modulate signaling initiated via receptors localized to caveolae. In the present study, we show that NO donors induced an increase in the monomeric form of this scaffolding protein in cultured endothelial cells, the effect mimicked by 8-bromo cGMP. Proximity imaging of endothelial cells transfected with the thermotolerant green fluorescent protein–caveolin-1 construct demonstrated that sodium nitroprusside resulted in the increased fluorescence ratio of 410:470 nm, consistent with the distancing of fluorescently tagged caveolin-1. Pulse labeling of endothelial cells with cholera toxin B subunit indicated that sodium nitroprusside reversibly decreased its binding. Signaling via G protein–coupled receptors resident to caveolae was inhibited by pretreatment with NO donor. The data demonstrate that NO modulation of cell signaling is accomplished in part by regulating the state of caveolin-1 oligomerization. NO-induced attenuation of signaling involves reversible dissociation of caveolin scaffold, thus providing both spatial and temporal modulation of signal transduction.
Increased collagenase activity in macrophages from bronchial lavage as a diagnostic marker of non-small cell lung cancer
Authors: Y Hakoda
Journal: Thorax (2003)

The roles of matrix metalloproteinases (MMPs) in cancer metastasis have been studied. Macrophages are considered to release MMPs in the tissues of patients with lung cancer.Intracellular collagenase activity was measured in CD14+ CD45+ cells from bronchial lavage fluid to establish a new diagnostic tool for lung cancer. Between August 2000 and November 2001 bronchoscopy and bronchial lavage were performed in 45 patients with abnormal shadows on the chest radiograph; 21 had lung cancer and 24 had non-malignant disease.Collagenase activity in patients with primary lung cancer (5.54 (0.65)) or non-small cell lung cancer (NSCLC) (5.62 (0.71)) was significantly higher than in those with non-malignant disease (3.63 (0.78), p=0.006 and p=0.008, respectively). Only three of 18 patients in the low activity group were diagnosed as having cancer compared with 18 of 27 in the high activity group (p=0.001). This significance was not seen in non-smokers but it was apparent in smokers/ex-smokers. Excluding non-smokers improved the specificity of collagenase activity in differentiating cancer and non-malignant disease from 62.5% to 80.0%. The sensitivity of the test was 85.7% in all patients and 88.2% in smokers/ex-smokers.Measurement of intracellular collagenase activity in macrophages in bronchial lavage fluid is a useful diagnostic tool for distinguishing between cancer and non-malignant diseases, especially in smokers and ex-smokers.
Enhanced Dopamine Transporter Density in Psychotropic-Naive Patients With Obsessive-Compulsive Disorder Shown by [<sup>123</sup>I]β-CIT SPECT
Authors: Nic J. van der Wee, Henk Stevens, Johannes A. Hardeman, Rene C. Mandl, Damiaan A. Denys, Harold J. van Megen, René S. Kahn, Herman M. Westenberg
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The authors examine the functional anatomy of serotonergic and dopaminergic systems in obsessive-compulsive disorder in psychotropic-naive patients without comorbidity. METHOD: [123I]β-CIT binding patterns for dopamine and serotonin transporters in the brain were measured in 15 psychotropic-naive adult outpatients with OCD (no comorbidity) and in 15 pairwise-matched healthy subjects. Volumes of interest were constructed on magnetic resonance imaging scans and coregistered with single photon emission computed tomography scans. Binding ratios were compared, and possible correlations between binding patterns and obsessive-compulsive symptoms were assessed. RESULTS: There were significant differences between patients and healthy subjects in the [123I]β-CIT binding pattern for dopamine transporter in the left caudate and left putamen. Patients had higher binding ratios than healthy subjects. No differences were found in the less specific [123I]β-CIT binding pattern for serotonin transporters in the selected volumes of interest. Hemispheric within-group comparisons revealed no asymmetry effects. CONCLUSIONS: The results of our study provide direct evidence for an involvement of the dopaminergic system in the pathophysiology of OCD.
Impact of Subclinical Atherosclerosis on Cardiovascular Disease Events in Individuals With Metabolic Syndrome and Diabetes
Authors: Shaista Malik, Matthew J. Budoff, Ronit Katz, Roger S. Blumenthal, Alain G. Bertoni, Khurram Nasir, Moyses Szklo, R. Graham Barr, Nathan D. Wong
Journal: Diabetes Care (2011)

OBJECTIVE While metabolic syndrome (MetS) and diabetes confer greater cardiovascular disease (CVD) risk, recent evidence suggests that individuals with these conditions have a wide range of risk. We evaluated whether screening for coronary artery calcium (CAC) and carotid intimal-medial thickness (CIMT) can improve CVD risk stratification over traditional risk factors (RFs) in people with MetS and diabetes. RESEARCH DESIGN AND METHODS We assessed CAC and CIMT in 6,603 people aged 45–84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). Cox regression examined the association of CAC and CIMT with coronary heart disease (CHD) and CVD over 6.4 years in MetS and diabetes. RESULTS Of the subjects, 1,686 (25%) had MetS but no diabetes and 881 (13%) had diabetes. Annual CHD event rates were 1.0% among MetS and 1.5% for diabetes. Ethnicity and RF-adjusted hazard ratios for CHD for CAC 1–99 to ≥400 vs. 0 in subjects with neither MetS nor diabetes ranged from 2.6 to 9.5; in those with MetS, they ranged from 3.9 to 11.9; and in those with diabetes, they ranged from 2.9 to 6.2 (all P &amp;lt; 0.05 to P &amp;lt; 0.001). Findings were similar for CVD. CAC increased the C-statistic for events (P &amp;lt; 0.001) over RFs and CIMT in each group while CIMT added negligibly to prediction over RFs. CONCLUSIONS Individuals with MetS or diabetes have low risks for CHD when CAC or CIMT is not increased. Prediction of CHD and CVD events is improved by CAC more than by CIMT. Screening for CAC or CIMT can stratify risk in people with MetS and diabetes and support the latest recommendations regarding CAC screening in those with diabetes.
IN VITRO ACTIVATION OF CELLULAR IMMUNE RESPONSE TO GROSS VIRUS-INDUCED LYMPHOMA
Authors: Manuel Ortiz de Landazuri, Ronald B. Herberman
Journal: The Journal of Experimental Medicine (1972)

Spleen cells from W/Fu rats 40 days or more after immunization with a syngeneic Gross virus-induced leukemia were unreactive in direct cytotoxic assays. Incubation of these immune cells at 37 degrees C for 12 hr or longer, in the absence of antigen, resulted in the appearance of specific cytotoxic reactivity. Other lymphoid cells from the immune rats also were activated upon in vitro incubation, but to a lesser extent. Experiments were performed to define the necessary conditions and the mechanism for the in vitro incubation. Activation was temperature dependent, occurring at 37 degrees C but not at 4 degrees C. Immune serum suppressed the activation, but normal rat serum also had some inhibitory activity. Passage of immune cells through a nylon column, before preincubation, prevented activation. In contrast, exposure to nylon after preincubation did not remove cytotoxic reactivity. These findings demonstrate the reversal of a central inhibition of immune cell activity. The explanations offered for this phenomenon included change in surface characteristics of the immune cells during in vitro incubation, and the possible need for an adherent helper cell.
HIV-1 Protease Inhibitor, Ritonavir
Authors: Takayuki Ikezoe, Yasuko Hisatake, Tamotsu Takeuchi, Yuji Ohtsuki, Yang Yang, Jonathan W. Said, Hirokuni Taguchi, H. Phillip Koeffler
Journal: Cancer Research (2004)

Abstract We previously showed that HIV-1 protease inhibitors (PIs) slowed the proliferation of human myeloid leukemia cells and enhanced their differentiation in the presence of all–trans-retinoic acid. In this study, we found that PIs, including ritonavir, saquinavir, and indinavir, inhibited the growth of DU145 and PC-3 androgen-independent prostate cancer cells as measured by a clonal proliferation assay. Recent studies showed that ritonavir inhibited cytochrome P450 3A4 enzyme (CYP3A4) in liver microsomes. The CYP3A4 is involved in drug metabolism and acquisition of drug resistance. To clarify the drug interaction between ritonavir and other anticancer drugs, we cultured DU145 cells with docetaxel either alone or in combination with ritonavir. Ritonavir enhanced the antiproliferative and proapoptotic effects of docetaxel in the hormonally independent DU145 prostate cancer cells in vitro as measured by the clonogenic soft agar assay and detection of the activated form of caspase-3 and cleavage of poly(ADP-ribose) polymerase using Western blot analysis. Real-time PCR showed that docetaxel induced the expression of CYP3A4 at the transcriptional level, and ritonavir (10−5 mol/L) completely blocked this induction. An ELISA-based assay also showed that ritonavir inhibited DNA binding activity of nuclear factor κB (NFκB) in DU145 cells, which is a contributor to drug resistance in cancer cells. Furthermore, combination treatment of docetaxel and ritonavir dramatically inhibited the growth of DU145 cells present as tumor xenografts in BNX nude mice compared with either drug alone. Importantly, docetaxel induced expression of CYP3A4 in DU145 xenografts, and ritonavir completely blocked this induction. Ritonavir also inhibited NFκB DNA binding activity in DU145 xenografts. Extensive histologic analyses of the liver, spleen, kidneys, bone marrow, skin, and subcutaneous fat pads from these mice showed no abnormalities. In summary, combination therapy of ritonavir and anticancer drugs holds promise for the treatment of individuals with advanced, drug resistant cancers.
Emergency Abdominal Surgery.
Authors: M R B KEIGHLEY
Journal: Gut (2000)

<h3>Abstract</h3> Public health recommendations aimed at limiting spread of SARS-CoV-2 have encouraged social distancing and masks as economies across the United States re-open. Understanding adherence to these guidelines will inform further efforts to reduce transmission. In this repeated cross-sectional survey study, we describe changes in social behavior in Ohio during periods of declining and rising cases. While essential activities remained consistent over time, more individuals attended gatherings of 10 or more people as cases rose, particularly in the 18-29 age group. A majority of individuals wore masks. It appears necessary to continue limiting gatherings and encourage mask-wearing, particularly among younger groups.
Common Origin and Evolution of Glycosyltransferases Using Dol-P-monosaccharides as Donor Substrate
Authors: Rafael Oriol, Ivan Martinez-Duncker, Isabelle Chantret, Rosella Mollicone, Patrice Codogno
Journal: Molecular Biology and Evolution (2002)

On the basis of the analysis of 64 glycosyltransferases from 14 species we propose that several successive duplications of a common ancestral gene, followed by divergent evolution, have generated the mannosyltransferases and the glucosyltransferases involved in asparagine-linked glycosylation (ALG) and phosphatidyl-inositol glycan anchor (PIG or GPI), which use lipid-related donor and acceptor substrates. Long and short conserved peptide motifs were found in all enzymes. Conserved and identical amino acid positions were found for the α2/6- and the α3/4-mannosyltransferases and for the α2/3-glucosyltransferases, suggesting unique ancestors for these three superfamilies. The three members of the α2-mannosyltransferase family (ALG9, PIG-B, and SMP3) and the two members of the α3-glucosyltransferase family (ALG6 and ALG8) shared 11 and 30 identical amino acid positions, respectively, suggesting that these enzymes have also originated by duplication and divergent evolution. This model predicts a common genetic origin for ALG and PIG enzymes using dolichyl-phospho-monosaccharide (Dol-P-monosaccharide) donors, which might be related to similar spatial orientation of the hydroxyl acceptors. On the basis of the multiple sequence analysis and the prediction of transmembrane topology we propose that the endoplasmic reticulum glycosyltransferases using Dol-P-monosaccharides as donor substrate have a multispan transmembrane topology with a first large luminal conserved loop containing the long motif and a small cytosolic conserved loop containing the short motif, different from the classical type II glycosyltransferases, which are anchored in the Golgi by a single transmembrane domain.
The epidemiology of glioma in adults: a "state of the science" review
Authors: Q. T. Ostrom, L. Bauchet, F. G. Davis, I. Deltour, J. L. Fisher, C. E. Langer, M. Pekmezci, J. A. Schwartzbaum, M. C. Turner, K. M. Walsh, M. R. Wrensch, J. S. Barnholtz-Sloan
Journal: Neuro-Oncology (2014)

Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors. Although relatively rare, they cause significant mortality and morbidity. Glioblastoma, the most common glioma histology (∼45% of all gliomas), has a 5-year relative survival of ∼5%. A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic analyses of glioma have also produced new evidence about risk and prognosis. Recently discovered biomarkers that indicate improved survival include O6-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine–phosphate–guanine island methylator phenotype. Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma. Many risk factors have been examined as potential contributors to glioma risk. Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s). The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results. We provide a "state of the science" review of current research into causes and risk factors for gliomas in adults.
Gene transefer as a new mode of vaccination: Implications for HCV
Authors: Jorge J. Gumucio, Michael W. McDonnell
Journal: Hepatology (1993)

Cytotoxic T lymphocytes (CTLs) specific for conserved viral antigens can respond to different strains of virus, in contrast to antibodies, which are generally strain-specific. The generation of such CTLs in vivo usually requires endogenous expression of the antigen, as occurs in the case of virus infection. To generate a viral antigen for presentation to the immune system without the limitations of direct peptide delivery or viral vectors, plasmid DNA encoding influenza A nucleoprotein was injected into the quadriceps of BALB/c mice. This resulted in the generation of nucleoproteinspecific CTLs and protection from a subsequent challenge with a heterologous strain of influenza A virus, as measured by decreased viral lung titers, inhibition of mass loss, and increased survival.
Adjuvant chemotherapy and survival in completely resected non-small cell lung cancer
Authors: S S Birring
Journal: Thorax (2004)

▴ The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med2004;350:351–60 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] The role of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC) is unclear. In this randomised controlled trial, patients with pathologically documented NSCLC (stages I–III) were assigned to either cisplatin based chemotherapy or observation within 60 days of surgery. The primary outcome … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DThe%2BInternational%2BAdjuvant%2BLung%2BCancer%2BTrial%2BColla%26rft.auinit1%253D%2B%26rft.volume%253D350%26rft.issue%253D4%26rft.spage%253D351%26rft.epage%253D360%26rft.atitle%253DCisplatin-Based%2BAdjuvant%2BChemotherapy%2Bin%2BPatients%2Bwith%2BCompletely%2BResected%2BNon-Small-Cell%2BLung%2BCancer%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa031644%26rft_id%253Dinfo%253Apmid%252F14736927%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa031644&link_type=DOI [3]: /lookup/external-ref?access_num=14736927&link_type=MED&atom=%2Fthoraxjnl%2F59%2F4%2F341.atom [4]: /lookup/external-ref?access_num=000188254800007&link_type=ISI
Autologous stem-cell transplantation in patients with mantle cell lymphoma beyond 65 years of age: a study from the European Group for Blood and Marrow Transplantation (EBMT)
Authors: E. Jantunen, C. Canals, M. Attal, K. Thomson, N. Milpied, A. Buzyn, A. Ferrant, P. Biron, C. Crawley, A. Schattenberg, J.J. Luan, H. Tilly, B. Rio, P.W. Wijermans, P. Dreger, A. Sureda
Journal: Annals of Oncology (2011)
Compliance with inhaled asthma medication in preschool children.
Authors: N A Gibson, A E Ferguson, T C Aitchison, J Y Paton
Journal: Thorax (1995)

BACKGROUND--Previous studies have shown poor compliance with regular drug therapy in children and adults with asthma. In preschool children the parents supervise and are responsible for drug administration, but little is known of compliance in this group. In addition, there are few data on the patterns of drug use of inhaled prophylactic asthma therapy or of the relation between compliance and symptom control. A study was undertaken to address these issues with the hypothesis that parental supervision would result in good compliance. METHODS--The subjects were 29 asthmatic children aged 15 months to five years already established on inhaled prophylactic medication delivered through a large volume spacer. The prescribed drug regimens varied between subjects. This was an observational study using an electronic inhaler timer device to record the date and time of each actuation of the aerosol canister. Diary cards were used for parallel recording of symptoms and parentally reported compliance with a drug regimen. RESULTS--Variable and generally poor compliance was demonstrated with a median of 50% of study days with full compliance (subject range 0-94%) and an overall median of 77% of prescribed doses of therapy taken during the study period. No relation was found between frequency of prescribed regimen and good compliance. Day care was associated with poorer compliance. No relation between good compliance and low symptom scores was found. CONCLUSION--Compliance with inhaled prophylactic therapy is poor in preschool children with asthma whose medication is administered under parental supervision.