tbuckley/cabot-search huggingface dataset:
Risk of Diabetes Mellitus in Long-Term Survivors of Hodgkin Lymphoma
Authors: Frederika A. van Nimwegen, Michael Schaapveld, Cecile P.M. Janus, Augustinus D.G. Krol, John M.M. Raemaekers, Leontien C.M. Kremer, Marilyn Stovall, Berthe M.P. Aleman, Flora E. van Leeuwen
Journal: Journal of Clinical Oncology (2014)

Purpose Recently, an increased risk of diabetes mellitus (DM) was observed after abdominal irradiation for childhood cancer. Because many Hodgkin lymphoma (HL) survivors have also been treated with infradiaphragmatic radiotherapy, we evaluated the association between HL treatment and DM risk. Patients and Methods Our study cohort comprised 2,264 5-year HL survivors, diagnosed before age 51 years and treated between 1965 and 1995. Treatment and follow-up information was collected from medical records and general practitioners. Radiation dosimetry was performed to estimate radiation dose to the pancreas. Cumulative incidence of DM was estimated, and risk factors for DM were evaluated by using Cox regression. Results After a median follow-up of 21.5 years, 157 patients developed DM. Overall cumulative incidence of DM after 30 years was 8.3% (95% CI, 6.9% to 9.8%). After para-aortic radiation with ≥ 36 Gy, the 30-year cumulative incidence of DM was 14.2% (95% CI, 10.7% to 18.3%). Irradiation with ≥ 36 Gy to the para-aortic lymph nodes and spleen was associated with a 2.30-fold increased risk of DM (95% CI, 1.54- to 3.44-fold) whereas para-aortic radiation alone with ≥ 36 Gy was associated with a 1.82-fold increased risk (95% CI, 1.02- to 3.25-fold). Lower doses (10 to 35 Gy) did not significantly increase risk of DM. The risk of DM significantly increased with higher mean radiation doses to the pancreatic tail (P &lt; .001). Conclusion Radiation to the para-aortic lymph nodes increases the risk of developing DM in 5-year HL survivors. Screening for DM should be considered in follow-up guidelines for HL survivors, and treating physicians should be alert to this increased risk.
Recurrent symptomatic pulmonary embolism caused by an infected Pudenz cerebrospinal fluid shunt device.
Authors: R T Gibney, F Donovan, M X Fitzgerald
Journal: Thorax (1978)

<h3>BACKGROUND AND PURPOSE:</h3> Identification of a partial/complete chemotherapy response in pediatric patients with intracranial germ cell tumors is clinically important for radiation treatment and management. Partial/complete response is conventionally determined on postcontrast MR imaging sequences. The purpose of this study was to assess the diagnostic utility of a balanced steady-state free precession sequence as an adjunct to standard MR imaging sequences for the detection of residual tumor in pediatric patients on postchemoreduction pre–radiation planning MR imaging. <h3>MATERIALS AND METHODS:</h3> This was a retrospective study of pediatric patients with intracranial germ cell tumors undergoing postchemotherapy, preradiotherapy MR imaging. Patients underwent 1.5T or 3T MR imaging with pre- and postcontrast T1WIs, T2WIs, and a balanced steady-state free precession sequence. Two neuroradiologists independently reviewed standard MR imaging sequences without the balanced steady-state free precession sequence, then with the balanced steady-state free precession sequence 1 week later. Assessment for partial/complete response was determined using Response Assessment in Neuro-Oncology criteria. A 5-point Likert scale scored the diagnostic confidence of the neuroradiologist rating each study without/with the balanced steady-state free precession sequence. Rates of residual disease concordance and diagnostic confidence levels without/with the balanced steady-state free precession sequence were calculated. <h3>RESULTS:</h3> Thirty-nine patients were included with 31 males and 8 females (mean age, 14.15 ± 4.26 years). Thirty-one patients had single-site disease; 8 patients had multisynchronous disease (47 sites in total). Compared to review of the standard MR sequences alone, the addition of the balanced steady state free precession sequence resulted in higher rates of tumor partial response categorization and greater diagnostic confidence levels (<i>P </i>&lt; .001, <i>P </i>&lt; .001). <h3>CONCLUSIONS:</h3> The balanced steady-state free precession sequence improves detection of residual chemotherapy-reduced intracranial germ cell tumors and increases diagnostic confidence of the neuroradiologist. The balanced steady-state free precession sequence may be an important adjunct to the standard MR imaging protocol for radiation planning.
Cyclin D1 Genotype, Response to Biochemoprevention, and Progression Rate to Upper Aerodigestive Tract Cancer
Authors: J. G. Izzo, V. A. Papadimitrakopoulou, D. D. Liu, P. L. C. den Hollander, I. M. Babenko, J. Keck, A. K. El-Naggar, D. M. Shin, J. J. Lee, W. K. Hong, W. N. Hittelman
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Altered cyclin D1 expression in advanced preinvasive lesions of the upper aerodigestive tract (UADT) is associated with an increased risk of developing cancer and histologic progression during and after combination biochemopreventive therapy (13-cis-retinoic acid, α-interferon, and α-tocopherol). Both alleles of the adenine (A)/guanine (G) cyclin D1 polymorphism located at nucleotide 870 encode two alternatively spliced transcripts, but the A allele preferentially encodes a protein with an extended half-life. We investigated whether the cyclin D1 genotype at nucleotide 870 was associated with baseline levels of cyclin D1 protein, post-treatment modulation of cyclin D1 protein levels, histologic response to treatment, and the outcome for subjects with preinvasive UADT lesions after biochemopreventive therapy. Methods: UADT tissue biopsy samples were obtained before and 6 and 12 months after biochemopreventive treatment from 31 individuals with advanced preinvasive UADT lesions. Tissues were examined for cyclin D1 genotype (by DNA single-strand conformation polymorphism analysis), for cyclin D1 protein expression (by immunohistochemistry), and for cyclin D1 gene copy number (by fluorescence in situ hybridization). Associations of cyclin D1 genotype with histologic response to therapy and time to progression to a higher degree of dysplasia or invasive cancer were investigated. All statistical tests were two-sided. Results: The A allele was associated with increased baseline cyclin D1 expression in the parabasal epithelial layer (16 of 18 AA/AG subjects versus four of nine GG subjects; P = .02), decreased histologic response to biochemopreventive treatment (six of 21 AA/AG subjects versus four of 10 GG subjects; P = .70), decreased favorable modulation of cyclin D1 expression by the treatment (seven of 18 AA/AG subjects versus eight of nine GG subjects; P = .02), and shorter progression-free survival (P = .05). Conclusions: The cyclin D1 A allele was associated with a diminished modulation of normal physiologic and treatment-induced decreased expression of cyclin D1, a decreased likelihood of response to biochemopreventive intervention, and an increased rate of progression to cancer development, findings that require validation in a larger cohort.
Hepatic Free Fatty Acids in Alcoholic Liver Disease and Morbid Obesity
Authors: Peter G. Mavrelis, Helmut V. Ammon, John J. Gleysteen, Richard A. Komorowski, Ursula K. Charaf
Journal: Hepatology (1983)

Alcoholic liver disease is characterized by the accumulation of fat and inflammatory changes in the liver. Because free fatty acids, the precursors of triglycerides, can damage biological membranes, accumulation of free fatty acids in the liver might be in part responsible for the functional and morphological changes seen in alcoholic liver disease. We, therefore, determined the hepatic lipid composition in biopsies from 31 patients with alcoholic liver disease, 18 patients with morbid obesity, and 5 patients without evidence of liver disease. Free fatty acids were found in all liver biopsies. Patients with morbid obesity or alcoholic liver disease had significantly higher fatty acid and triglyceride levels than did controls (p &amp;lt;, 0.01). Patients with alcoholic liver disease had significantly higher fatty acid levels than did patients with morbid obesity (p &amp;lt; 0.05), while there was no difference in the triglyceride concentrations between these two groups. The distribution of the fatty acids in the free fatty acid fraction differed significantly from that in the triglyceride fraction indicating a preferential incorporation of unsaturated fatty acids into triglycerides. This difference in the distribution pattern was lost in patients with the most severe forms of alcoholic liver disease. The data are consistent with the hypothesis that accumulation of free fatty acids in patients with alcoholic liver disease may be responsible for or contribute to the observed functional and morphological damages.
Histone deacetylase 2–mediated deacetylation of the glucocorticoid receptor enables NF-κB suppression
Authors: Kazuhiro Ito, Satoshi Yamamura, Sarah Essilfie-Quaye, Borja Cosio, Misako Ito, Peter J. Barnes, Ian M. Adcock
Journal: The Journal of Experimental Medicine (2005)

Glucocorticoids are the most effective antiinflammatory agents for the treatment of chronic inflammatory diseases even though some diseases, such as chronic obstructive pulmonary disease (COPD), are relatively glucocorticoid insensitive. However, the molecular mechanism of this glucocorticoid insensitivity remains uncertain. We show that a defect of glucocorticoid receptor (GR) deacetylation caused by impaired histone deacetylase (HDAC) 2 induces glucocorticoid insensitivity toward nuclear factor (NF)-κB–mediated gene expression. Specific knockdown of HDAC2 by RNA interference resulted in reduced sensitivity to dexamethasone suppression of interleukin 1β–induced granulocyte/macrophage colony-stimulating factor production. Loss of HDAC2 did not reduce GR nuclear translocation, GR binding to glucocorticoid response element (GRE) on DNA, or GR-induced DNA or gene induction but inhibited the association between GR and NF-κB. GR becomes acetylated after ligand binding, and HDAC2-mediated GR deacetylation enables GR binding to the NF-κB complex. Site-directed mutagenesis of K494 and K495 reduced GR acetylation, and the ability to repress NF-κB–dependent gene expression becomes insensitive to histone deacetylase inhibition. In conclusion, we show that overexpression of HDAC2 in glucocorticoid-insensitive alveolar macrophages from patients with COPD is able to restore glucocorticoid sensitivity. Thus, reduction of HDAC2 plays a critical role in glucocorticoid insensitivity in repressing NF-κB–mediated, but not GRE-mediated, gene expression.
Cytokine Profile and Correlation to the APACHE III and MPM II Scores in Patients with Sepsis
Authors: ELISABETH PRESTERL, THOMAS STAUDINGER, MARIA PETTERMANN, ANDREA LASSNIGG, HEINZ BURGMANN, STEFAN WINKLER, MICHAEL FRASS, WOLFGANG GRANINGER
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

In 35 patients fulfilling the criteria of systemic inflammatory response syndrome (SIRS) of infectious origin, tumor necrosis factor- α (TNF- α ), interleukin-6 (IL-6), tumor necrosis factor-soluble receptor (TNF-sR), and interleukin-12 (IL-12), C-reactive protein (CRP) levels and the Acute Physiology, And Chronic Health Evaluation III score (APACHE III) were determined on days 1 to 7, 14, 21, and 28. The Mortality Probability Models (MPM) II sepsis score was assessed at the time of admission into the study. The MPM II sepsis score correlated with IL-6 plasma levels on day 1. The APACHE III scores correlated with plasma levels of TNF-sR on days 2–7, with IL-6 levels on days 3–7, and with CRP levels on days 4–7 (p < 0.01). The MPM II sepsis score, the APACHE III score, and the IL-6, TNF-sR, and CRP levels were significantly different between survivors and nonsurvivors and between patients with and without shock (p < 0.05). A significant decrease of the APACHE III scores, IL-6, and CRP levels was observed over the study period in the survivor group only (p < 0.05), while neither the dynamics of TNF- α nor IL-12 plasma levels contributed to the risk estimation of mortality.
Defining obesity hypoventilation syndrome
Authors: Aiman Tulaimat, Stephen Littleton
Journal: Thorax (2014)

The definition of obesity hypoventilation syndrome (OHS) proposed by Hart et al 1 raises two questions that we have tried to answer briefly in this letter. 

First, previous definitions of OHS included obstructive sleep apnoea (OSA); Hart et al have excluded it. Why? OSA is present in most patients with OHS and is partly responsible for the hypercapnia.2 We believe that it is …
Physical activity, nutritional status and systemic inflammation in COPD
Authors: Pierantonio Laveneziana, Paolo Palange
Journal: European Respiratory Journal (2012)

ERS) Research Seminar entitled ''Physical activity, nutritional status and systemic inflammation in COPD'' and organised by the "Clinical Physiology and Exercise" ERS scientific group 4.01, brought together international experts to discuss several important aspects of physical activity, nutritional status and inflammation in chronic obstructive pulmonary disease (COPD) including pathology and pathophysiology, measurement, and clinical and therapeutic implications.
A20 takes on tumors: tumor suppression by an ubiquitin-editing enzyme
Authors: Barbara A. Malynn, Averil Ma
Journal: The Journal of Experimental Medicine (2009)

Many B cell cancers are characterized in part by the dysregulation of the NF-κB signaling pathway. A new study identifies somatic mutations in TNFAIP3, the gene encoding the NF-κB inhibitor A20, in Hodgkin lymphomas and primary mediastinal lymphomas. These data reveal the role of A20 as a tumor suppressor protein.
US College Students' Use of Tobacco Products
Authors: Nancy A. Rigotti, Jae Eun Lee, Henry Wechsler
Journal: JAMA (2000)

ContextAdults aged 18 to 24 years, many of whom are in college, represent the youngest legal targets for tobacco industry marketing. Cigarette smoking has been described among college students, but little is known about noncigarette tobacco use by college students or cigar use by adults of any age.ObjectivesTo assess the prevalence of all forms of tobacco use (cigarettes, cigars, pipes, and smokeless tobacco) among US college students and to identify student- and college-level factors associated with use of each product.DesignThe Harvard College Alcohol Survey, a self-administered survey conducted in 1999.SettingOne hundred nineteen nationally representative US 4-year colleges.SubjectsA total of 14,138 randomly selected students (60% response rate).Main Outcome MeasuresSelf-report of current (in the past 30 days), past-year, and lifetime use of cigarettes, cigars, pipes, smokeless tobacco, and all tobacco products.ResultsNearly half (45.7%) of respondents had used a tobacco product in the past year and one third (32.9%) currently used tobacco. Cigarettes accounted for most of the tobacco use (28.5% current prevalence), but cigar use was also substantial (37.1% lifetime prevalence, 23.0% past-year prevalence, and 8.5% current prevalence) and combinations of the 2 were common. Total tobacco use was higher in men than in women (37.9% vs 29.7%; P&lt;.001), despite nearly identical current cigarette smoking rates between the sexes (28.5% for women vs 28.4% for men), because of greater use of cigars (current prevalence, 15.7% vs 3.9%; P&lt;.001) and smokeless tobacco (current prevalence, 8.7% vs 0.4%; P&lt;.001) by men. Tobacco use was significantly higher among white students (P&lt;.001), users of other substances (alcohol and marijuana) (P&lt;.001), and students whose priorities were social rather than educational or athletic (P&lt;.05). Among students who had used both cigars and cigarettes, only 8.9% smoked cigars at an earlier age than they had smoked cigarettes.ConclusionOur study indicates that tobacco use is common among college students and is not limited to cigarettes. College appears to be a time when many students are trying a range of tobacco products and are in danger of developing lifelong nicotine dependence. National efforts to monitor and reduce tobacco use of all types should expand to focus on college students and other young adults.
Manifestation of Hyperplastic Alveolar Nodules and Mammary Tumors in “Viable Yellow” and Non-yellow Mice
Authors: George L. Wolff, Daniel Medina, Robert L. Umholtz
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Manifestation of Hyperplastic Alveolar Nodules and Mammary Tumors in “Viable Yellow” and Non-yellow Mice Get access George L. Wolff, George L. Wolff 2National Center for Toxicological Research, Food and Drug Administration, Public Health Service, U.S. Department of Health, Education, and Welfare, Jefferson, Ark. 72079. Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniel Medina, Daniel Medina 3Department of Cell Biology, Baylor College of Medicine, Texas Medical Center, Houston, Tex. 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert L. Umholtz Robert L. Umholtz 2National Center for Toxicological Research, Food and Drug Administration, Public Health Service, U.S. Department of Health, Education, and Welfare, Jefferson, Ark. 72079. 4We acknowledge the technical assistance of Ms. Frances Shepherd and Mr. Olen E. Domon in this study. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 63, Issue 3, September 1979, Pages 781–785, https://doi.org/10.1093/jnci/63.3.781 Published: 01 September 1979 Article history Received: 27 October 1978 Accepted: 27 March 1979 Published: 01 September 1979
Long-term Effects of Cognitive Training on Everyday Functional Outcomes in Older Adults
Authors: Sherry L. Willis, Sharon L. Tennstedt, Michael Marsiske, Karlene Ball, Jeffrey Elias, Kathy Mann Koepke, John N. Morris, George W. Rebok, Frederick W. Unverzagt, Anne M. Stoddard, Elizabeth Wright, for the ACTIVE Study Group
Journal: JAMA (2006)

ECLINE IN COGNITIVE ABILI-ties has been shown to lead to an increased risk of difficulty in performing instrumental activities of daily living (IADL). 1-5However, whether interventions to maintain or enhance cognitive abilities in older adults will prevent or delay these functional difficulties is unclear.Prior interventions with older adults have targeted those with cognitive deficits or functional disabilities and have focused on remediation rather than prevention. 6,7rior studies have shown that cognitive interventions can improve cognitive abilities in normal elders but have not included functional outcome measures and have been limited by small, homogeneous samples and lack of randomization.
Wotherspoon criteria combined with B cell clonality analysis by advanced polymerase chain reaction technology discriminates covert gastric marginal zone lymphoma from chronic gastritis
Authors: M Hummel, S Oeschger, T F E Barth, C Loddenkemper, S B Cogliatti, A Marx, H-H Wacker, A C Feller, H-W Bernd, M-L Hansmann, H Stein, P Möller
Journal: Gut (2006)

<b>Background and aims:</b> Gastric mucosa associated lymphoid tissue lymphoma is a well defined B cell lymphoma yet often impossible to distinguish from severe chronic gastritis on morphological grounds alone. Therefore, it was suggested to use the clonality of the immunoglobulin (Ig) heavy chain (H) genes, as detected by polymerase chain reaction (PCR), as a decisive criterion. However, there is controversy as to whether B cell clonality also exists in chronic gastritis, hence rendering this approach futile at present. <b>Methods:</b> An expert panel re-examined the histology and immunohistochemistry of a total of 97 cases of gastric biopsies, including clearcut marginal zone lymphoma, chronic gastritis, and ambiguous cases, applying the Wotherspoon criteria on the basis of haematoxylin-eosin and CD20 immunostainings. In addition, a new and advanced PCR system for detection of clonal IgH gene rearrangements was independently applied in two institutions in each case. <b>Results:</b> The overall IgH clonality assessments of both institutions were in total agreement. Overt lymphoma (Wotherspoon score 5) was clonal in 24/26 cases. Chronic gastritis (Wotherspoon scores 1 and 2) was not clonal in 52/53 cases; the clonal case being Wotherspoon score 2. Of 18 cases with ambiguous histology (Wotherspoon scores 3 and 4) four were clonal. <b>Conclusions:</b> Using advanced PCR technology, clonal gastritis is extremely rare, if it exists at all. Thus B cell clonality in Wotherspoon 3 and 4 cases is regarded as suitable for definitively diagnosing gastric marginal zone lymphoma.
Inhibition of cyclic flow variations in stenosed canine coronary arteries by thromboxane A2/prostaglandin H2 receptor antagonists.
Authors: J H Ashton, J M Schmitz, W B Campbell, M L Ogletree, S Raheja, A L Taylor, C Fitzgerald, L M Buja, J T Willerson
Journal: Circulation Research (1986)

We tested the hypothesis that thromboxane A2 and thromboxane A2/PGH2 receptor occupation are important in mediating cyclical reductions in coronary blood flow (CFVs) in concentrically narrowed canine coronary arteries. Two potent and selective thromboxane A2/PGH2 receptor antagonists, SQ29,548 and SQ28,668 eliminated CFVs and restored a normal pattern of blood flow through the severely narrowed vessels in 77 and 75% of the dogs, respectively. CFVs were eliminated within several minutes of an intravenous bolus injection of SQ29,548 or SQ28,688. A continuous infusion of SQ29,548 (0.2 mg/kg X min) prevented the recurrence of CFVs throughout the duration of its infusion. Left atrial infusion of the thromboxane A2 mimetic, U46619, restored CFVs in 5 of 8 SQ29,548-treated and in 5 of 7 SQ28,668-treated dogs. Circulating concentrations of the stable metabolites of TxA2 and PGI2, TxB2 and 6-keto-PGF1 alpha, respectively, were unaffected by administration of SQ29,548. However, stenosed vascular segments of the left anterior descending coronary artery (LAD) of SQ29,548-treated dogs produced significantly less thromboxane A2 than comparable segments from untreated dogs. Morphologic studies showed that stenosed coronary arteries in which CFVs had been abolished by either SQ29,548 or SQ28,668 had relatively few adherent platelets, whereas comparable coronary segments removed from untreated animals had relatively large, platelet-rich mural thrombi. SQ29,548 did not alter the synthesis of TxB2 by platelets. 6-keto-PGF1 alpha concentrations in the stenosed LAD and nonstenosed circumflex coronary arteries were not altered by SQ29,548 administration. These data suggest that the thromboxane A2/PGH2 receptor antagonists, SQ29,548 and SQ28,688, inhibit cyclic reductions in coronary blood flow in this model by preventing the accumulation of platelets at the site of a critical coronary arterial stenosis. The data also suggest that TxA2 is important in mediating the interaction between platelets and the constricted coronary artery that is responsible for the development and maintenance of CFVs in this experimental model.