tbuckley/cabot-search huggingface dataset:
Immunobiology of CR2, the B Lymphocyte Receptor for Epstein-Barr Virus and the C3d Complement Fragment
Authors: N R Cooper, M D Moore, G R Nemerow
Journal: Annual Review of Immunology (1988)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Nontuberculous Mycobacterial Disease in Patients with HIV in Southeast Asia
Authors: Kimberly D. McCarthy, Kevin P. Cain, Kevin L. Winthrop, Nibondh Udomsantisuk, Nguyen T. N. Lan, Borann Sar, Michael E. Kimerling, Nong Kanara, Lut Lynen, Patama Monkongdee, Theerawit Tasaneeyapan, Jay K. Varma
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Although nontuberculous mycobacteria (NTM) are widely documented as a cause of illness among HIV-infected people in the developed world, studies describing the prevalence of NTM disease among HIV-infected people in most resource-limited settings are rare.To evaluate the prevalence of mycobacterial disease in HIV-infected patients in Southeast Asia.We enrolled people with HIV from three countries in Southeast Asia and collected pulmonary and extrapulmonary specimens to evaluate the prevalence of mycobacterial disease. We adapted American Thoracic Society/Infectious Disease Society of America guidelines to classify patients into NTM pulmonary disease, NTM pulmonary disease suspects, NTM disseminated disease, and no NTM categories.In Cambodia, where solid media alone was used, NTM was rare. Of 1,060 patients enrolled in Thailand and Vietnam, where liquid culture was performed, 124 (12%) had tuberculosis and 218 (21%) had NTM. Of 218 patients with NTM, 66 (30%) were classified as NTM pulmonary disease suspects, 9 (4%) with NTM pulmonary disease, and 10 (5%) with NTM disseminated disease. The prevalence of NTM disease was 2% (19 of 1,060). Of 51 patients receiving antiretroviral therapy (ART), none had NTM disease compared with 19 (2%) of 1,009 not receiving ART.Although people with HIV frequently have sputum cultures positive for NTM, few meet a strict case definition for NTM disease. Consistent with previous studies, ART was associated with lower odds of having NTM disease. Further studies of NTM in HIV-infected individuals in tuberculosis-endemic countries are needed to develop and validate case definitions.
Doxorubicin Directs the Accumulation of Interleukin-12–Induced IFNγ into Tumors for Enhancing STAT1–Dependent Antitumor Effect
Authors: Shiguo Zhu, Marian Waguespack, Steven A. Barker, Shulin Li
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To examine the mechanism by which doxorubicin plus interleukin-12 (IL-12) gene transfer induces enhanced therapeutic efficacy against tumors. Experimental Design: Tumor-bearing mice were treated with doxorubicin, IL-12–encoding plasmid DNA, doxorubicin plus IL-12–encoding plasmid DNA, or plasmid DNA control. Doxorubicin was systemically given via i.p. injection, and IL-12 was systemically expressed via i.m. injection. To show that doxorubicin enhances the accumulation of IL-12–induced IFNγ into tumors and the signal transducer and activator of transcription 1 (Stat1)–dependent antitumor efficacy, the distribution of IFNγ and the therapeutic end points, such as T-cell infiltration, inhibition of tumor vessel density, tumor growth inhibition, and inhibition of spontaneous tumor metastasis in wild-type and Stat1−/− host and tumors were determined after the treatment at the indicated time points. Results: In this study, a novel mechanism was unveiled. We discovered that doxorubicin enhances the accumulation of IL-12–induced IFNγ in tumors. The doxorubicin-mediated accumulation of IFNγ in tumors is caused by an increased accumulation of IFNγ-secreting immune cells and not by a direct translocation of IFNγ protein into tumors. Depletion of immune cells reverses the doxorubicin-mediated accumulation of IFNγ into tumors and reverses the inhibition of tumor vessel density induced by coadministration of doxorubicin and IL-12 DNA. Knocking out IFNγ signaling in the tumor host reverses the significant inhibition of tumor growth by coadministration of doxorubicin and IL-12. Conclusions: The enhanced antitumor efficacy by coadministration of doxorubicin and IL-12 is dependent on the accumulation of IFNγ in tumors. This discovery provides a possible strategy to reduce side effects caused by IL-12.
Lymphoma risk in systemic lupus: effects of disease activity versus treatment
Authors: Sasha Bernatsky, Rosalind Ramsey-Goldman, Lawrence Joseph, Jean-Francois Boivin, Karen H Costenbader, Murray B Urowitz, Dafna D Gladman, Paul R Fortin, Ola Nived, Michelle A Petri, Soren Jacobsen, Susan Manzi, Ellen M Ginzler, David Isenberg, Anisur Rahman, Caroline Gordon, Guillermo Ruiz-Irastorza, Edward Yelin, Sang-Cheol Bae, Daniel J Wallace, Christine A Peschken, Mary Anne Dooley, Steven M Edworthy, Cynthia Aranow, Diane L Kamen, Juanita Romero-Diaz, Anca Askanase, Torsten Witte, Susan G Barr, Lindsey A Criswell, Gunnar K Sturfelt, Irene Blanco, Candace H Feldman, Lene Dreyer, Neha M Patel, Yvan St Pierre, Ann E Clarke
Journal: Annals of the Rheumatic Diseases (2013)

To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE).
A polyalanine peptide with only five native myelin basic protein residues induces autoimmune encephalomyelitis.
Authors: A M Gautam, C I Pearson, D E Smilek, L Steinman, H O McDevitt
Journal: The Journal of Experimental Medicine (1992)

The minimum structural requirements for peptide interactions with major histocompatibility complex (MHC) class II molecules and with T cell receptors (TCRs) were examined. In this report we show that substituting alanines at all but five amino acids in the myelin basic protein (MBP) peptide Ac1-11 does not alter its ability to bind A alpha uA beta u (MHC class II molecules), to stimulate specific T cells and, surprisingly, to induce experimental autoimmune encephalomyelitis (EAE) in (PL/J x SJL/J)F1 mice. Most other amino acid side chains in the Ac1-11 peptide are essentially irrelevant for T cell stimulation and for disease induction. Further analysis revealed that binding to A alpha uA beta u occurred with a peptide that consists mainly of alanines and only three of the original residues of Ac1-11. Moreover, when used as a coimmunogen with MBP Ac1-11, this peptide inhibited EAE. The finding that a specific in vivo response can be generated by a peptide containing only five native residues provides evidence that disease-inducing TCRs recognize only a very short sequence of the MHC-bound peptide.
The Ratio of Serum Eicosapentaenoic Acid to Arachidonic Acid Is Associated With Renal Impairment and Diabetic Macroangiopathies in Elderly Patients With Type 2 Diabetes
Authors: Hiroyuki Ito, Hiroshi Ohira, Toshiya Chinen, Takashi Omoto, Masahiro Shinozaki, Shinya Nishio, Mariko Abe, Shinichi Antoku, Mizuo Mifune, Michiko Toagane
Journal: Diabetes Care (2013)

A low ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) has been reported to correlate with coronary heart disease (1–3), and no previous studies have investigated serum polyunsaturated fatty acid (PUFA) levels exclusively in patients with diabetes, in whom atherosclerotic diseases are commonly found. We therefore examined the association between serum EPA/AA ratio and the prevalence of diabetic angiopathies in patients with type 2 diabetes.

The serum levels of EPA and AA were determined in 744 Japanese patients with type 2 diabetes (aged 67 ± 12 years, 60% males, duration of diabetes 13 ± 11 years, estimated glomerular filtration rate [eGFR] 78 ± 32 mL/min/1.73 m2, serum EPA 79.6 ± 52.6 μg/mL, serum AA 189.5 ± 55.0 μg/mL) and in 285 age- and sex-matched subjects without diabetes between October and December 2012. …
A SPECIFIC INHIBITOR FOR HUMAN DESOXYRIBONUCLEASE AND AN INHIBITOR OF THE LUPUS ERYTHEMATOSUS CELL PHENOMENON FROM LEUCOCYTES 1
Authors: Nathaniel B. Kurnick, Lawrence I. Schwartz, Sanford Pariser, Stanley L. Lee
Journal: Journal of Clinical Investigation (1953)

In speculating upon the probable role of desoxy- ribonuclease (DNase) in the depolymerization of desoxyribonucleic acid (DNA), which character- izes (1) the "lupus erythematosus (L.E.) cell" (2), we have suggested (3), as have Klemperer and his associates (4), that an increased serum en- zyme activity, potentiation of an intracellular DNase, or destruction of an intracellular inhibitor of DNase by a serum factor, might be responsible.In a previous communication (5) we reported evi- dence which excludes the serum DNase from re- sponsibility for the phenomenon.Studies on the interaction of leucocytes and serum, in an ap- proach to the alternative possibilities, disclosed the presence of a specific intracellular inhibitor of hu- man serum DNase and an inhibitor of the "L.E.cell" phenomenon (6, 7).In the present paper, we shall report upon some of the characteristics of these factors. I. SERUM DNAsE INHIBITIONA. Preparation of leucocyte extracts Leucocytes (WBC) were prepared with the aid of Bovine fraction I from heparinized blood as previously described (5) or by centrifugation at 0 to 2°C of fresh "ACD" bloods (120 ml. of 1.47 per cent dextrose, 1.32 per cent sodium citrate, 0.48 per cent citric acid plus 480
A heparin‐like anticoagulant in an 8‐month‐old boy with acute monoblastic leukemia
Authors: James B. Bussel, Peter G. Steinherz, Denis R. Miller, Margaret W. Hilgartner
Journal: American Journal of Hematology (1984)

Abstract An 8‐month‐old male with acute monoblastic leukemia died during induction chemotherapy of severe bleeding refractory to repeated infusions of platelets and clotting factors. A heparin effect was suggested by prothrombin time (PT) of 26 seconds, partial thromboplastin time (PTT) of 94 seconds, thrombin time 240 seconds, and reptilase time 18.4 seconds, with a fibrinogen of 88 mg/dl. Both plasma mixed with the patient's urine and the patient's plasma had their thrombin times corrected toward normal by both PF4 and protamine. Synergism of of the anticoagulant with antithrombin III was demonstrated not only by enhanced inhibition of thrombin but also by an increased rate of formation of thrombin‐antithrombin III complexes in the presence of the anticoagulant, which was eliminated by preincubation with heparinase. Since the anticoagulant activity was not found in the blasts themselves, it is presumed that the anticoagulant is heparin/heparan liberated from the endothelial lining by products of the cell destruction secondary to chemotherapy.
Outcome of wheeze in childhood: the influence of atopy
Authors: S Ross, DJ Godden, M Abdalla, D McMurray, A Douglas, D Oldman, JA Friend, JS Legge, JG Douglas
Journal: European Respiratory Journal (1995)

We have previously demonstrated that the adult outcome of childhood asthma differs from that of wheeze occurring only in the presence of infection. This paper examines the role of atopy in relation to outcome. We investigated the atopic status, current symptoms and bronchial reactivity to methacholine of 235 subjects aged 34-40 yrs, originally classified at age 10-15 yrs as having asthma (asthma group), wheeze only in the presence of infection (wheezy group), or no respiratory symptoms (comparison group). Subjects from the original asthma group were more likely to be atopic as defined by skin test reactivity, total serum immunoglobulin E (IgE) measurement or specific IgE radio allergosorbent test (RAST) measurement than those from the wheezy group. The wheezy group differed significantly from the reference group only in RAST results, when other variables were taken into account. In a logistic regression model, the important independent predictors for adult wheezing symptoms were original group, atopy and current smoking. Methacholine responsiveness was independently associated with original group (the asthma group were more likely to respond positively), atopy and female gender. The results suggest that atopy is an important predictor for wheeze and bronchial hyperreactivity in middle age. However, the difference in outcome for children who had asthma compared to those who had wheeze only in the presence of infection cannot be explained by atopy alone.
Phase II study of troxacitabine in chemotherapy-naïve patients with advanced cancer of the pancreas
Authors: R. Lapointe, R. Létourneau, W. Steward, R.E. Hawkins, G. Batist, M. Vincent, R. Whittom, M. Eatock, J. Jolivet, M. Moore
Journal: Annals of Oncology (2005)
Tuberculin skin test size and risk of tuberculosis: A 12-year follow-up of contacts of TB cases
Authors: Onofre Morán-Mendoza, Mark FitzGerald, Kevin Elwood, David Patrick
Journal: European Respiratory Journal (2011)

Background: There are no long-term cohort studies assessing the risk of developing active TB according to the tuberculin skin test size in contacts of TB cases who did not receive treatment for latent TB infection (LTBI).

Objective: To assess the risk of TB – according to the tuberculin skin test (TST) size in contacts of active TB cases who did not receive LTBI treatment.

Methods: This is a population-based retrospective cohort study of contacts of active TB cases recorded in British Columbia, Canada. We estimated the up to 12-year risk of developing TB for infected and non-infected contacts, -according to tuberculin skin test size- using incidence rates. Contacts with HIV infection or with previous TB were excluded.

Results: Among 26,542 contacts, 180 individuals developed TB (tuberculosis rate 678/100,000). Non-infected Household contacts (tuberculin skin test size 0-4 mm) had a TB rate of 1,014/100,000; those with a TST of 5-9 mm a TB rate of 2,162/100,000; and those with 10-14 mm a rate of 4,478/100,000.

Non-infected Close non-household contacts had a TB rate of 222/100,000; those with a TST of 5-9 mm a TB rate of 296/100,000 and those with 10-14 mm a rate of 1,821/100,000.

Non-infected Casual contacts had a TB rate of 83/100,000; those with a TST of 5-9 mm a TB rate of 204/100,000 and those with 10-14 mm a rate of 860/100,000.

Conclusion: The risk of TB increases with TST size in all contacts; especially with close contacts. TB risk is high for all household contacts, including those considered non-infected. The risk of TB in non-household contacts is significant only when the TST is >10 mm.
Steroid Pretreatment of Organ Donors to Prevent Postischemic Renal Allograft Failure
Authors: Alexander Kainz, Julia Wilflingseder, Christa Mitterbauer, Maria Haller, Christopher Burghuber, Paul Perco, Robert M. Langer, Georg Heinze, Rainer Oberbauer
Journal: Annals of Internal Medicine (2010)

Posttransplantation acute renal failure (ARF) occurs in roughly 25% of recipients of organs from deceased donors. Inflammation in the donor organ is associated with risk for ARF.To determine whether administering corticosteroids to deceased organ donors reduces the incidence and duration of ARF in organ recipients more than placebo.Parallel, blocked randomized trial, performed between February 2006 and November 2008, with computer-generated randomization and centralized allocation. Investigators were masked to group assignment. (Controlled-trials.com registration number: ISRCTN78828338) SETTING: 3 renal transplantation centers in Austria and Hungary.306 deceased heart-beating donors and 455 renal transplant recipients.Organ donors were administered an intravenous infusion of either 1000 mg of methylprednisolone (136 donors) or placebo (0.9% saline) (133 donors) at least 3 hours before organ harvesting.Incidence of ARF, defined as more than 1 dialysis session in the first week after transplantation, was the primary end point. Secondary and other end points included duration of ARF and trajectories of serum creatinine level. The suppression of immune response and inflammation by the intervention was assessed in the donor organ on a genome-wide basis.52 of 238 recipients (22%) of kidneys from steroid-treated donors and 54 of 217 recipients (25%) of kidneys from placebo-treated donors had ARF (difference, 3 percentage points [95% CI, -11 to 5 percentage points]). One graft was lost on day 1 in each group, and 1 recipient in the placebo group died of cardiac arrest on day 2. The median duration of ARF was 5 days (interquartile range, 2 days) in the steroid group and 4 days (interquartile range, 2 days) in the placebo group (P = 0.31). The groups had similar trajectories of serum creatinine level in the first week (P = 0.72). Genomic analysis showed suppressed inflammation and immune response in kidney biopsies from deceased donors who received corticosteroids.Donors and recipients were mainly white, and all were from 3 transplantation centers in central Europe, which may limit generalizability.Systemic suppression of inflammation in deceased donors by corticosteroids did not reduce the incidence or duration of posttransplantation ARF in allograft recipients.Austrian Science Fund and Austrian Academy of Science.
Lung function in white children aged 4 to 19 years: I--Spirometry.
Authors: M Rosenthal, S H Bain, D Cramer, P Helms, D Denison, A Bush, J O Warner
Journal: Thorax (1993)

A study was performed to produce reference standards for spirometric lung function in white children and to calculate standard deviation scores adjusted for gender and pubertal stage.A cross sectional study was made of 772 white children aged 4.6 to 18.8 years (455 male) tested on an OHIO 840 spirometer and assessed anthropometrically and pubertally.Before puberty there was a linear increase in all lung function measurements with height. During puberty a sudden increase occurred, but subsequently the relationship was again linear. No simple single equation described this pattern. Advanced puberty in younger children conferred a respiratory advantage, whilst delayed puberty resulted in the converse. Girls had poorer volumes per unit height, but young girls had superior airflow/unit lung volume. In both sexes lung volumes and flows bore a constant relationship to external thoracic dimensions.Puberty has a dramatic effect on lung function. Regression equations for predicted values of lung function measurements and for calculation of standard deviation scores are given (with pubertal correction factors) for each gender.
Statin use and risk of community acquired pneumonia in older people: population based case-control study
Authors: S. Dublin, M. L Jackson, J. C Nelson, N. S Weiss, E. B Larson, L. A Jackson
Journal: BMJ (2009)

<b>Objective</b> To test the hypothesis that hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) may decrease the risk of community acquired pneumonia. <b>Design</b> Population based case-control study. <b>Setting</b> Group Health, a large integrated healthcare delivery system. <b>Population</b> Immunocompetent, community dwelling Group Health members aged 65 to 94; two matched controls for each case with pneumonia. Information on comorbid illnesses and functional and cognitive status, potential confounders of the association between statin use and risk of pneumonia, came from medical record review and computerised pharmacy data. <b>Main outcome measure</b> Adjusted estimates of risk of pneumonia in relation to current statin use. <b>Results</b> 1125 validated cases of pneumonia and 2235 matched controls were identified. Compared with controls, cases were more likely to have chronic lung and heart disease, especially severe disease, and functional or cognitive impairment. Current statin use was present in 16.1% (181/1125) of cases and 14.6% (327/2235) of controls (adjusted odds ratio 1.26, 95% confidence interval 1.01 to 1.56). Among cases admitted to hospital and matched controls, current statin use was present in 17.2% (68/395) of cases and 14.2% (112/788) of controls (adjusted odds ratio 1.61, 1.08 to 2.39, compared with non-use). In people in whom statins were indicated for secondary prevention, the adjusted odds ratio for risk of pneumonia in relation to current statin use was 1.25 (0.94 to 1.67); in those with no such indication, it was 0.81 (0.46 to 1.42). <b>Conclusions</b> Statin use was not associated with decreased risk of pneumonia among immunocompetent, community dwelling older people. Findings of previous studies may reflect “healthy user” bias.
Phase II Study of Vinflunine in Malignant Pleural Mesothelioma
Authors: Denis C. Talbot, Jacques Margery, Gérard Dabouis, Graham Dark, Henry Taylor, Hélène Boussemart, Véronique Cadic, Marie-Claire Pinel, Alain Rivière, Liliane Ollivier, Pierre Ruffié
Journal: Journal of Clinical Oncology (2007)

Malignant pleural mesothelioma (MPM) is a disease of increasing incidence for which treatment options are limited. This study reports the clinical efficacy data for vinflunine, a novel microtubule inhibitor, in MPM.Patients with a histologically confirmed diagnosis of MPM were eligible for enrollment onto this multicenter phase II trial if they had not received prior chemotherapy or radiotherapy and had measurable lesions by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Vinflunine 320 mg/m2 by 10-minute intravenous infusion was administered on day 1 of 21-day cycles. Modifications of dose and schedule were made according to National Cancer Institute Common Toxicity Criteria version 2.0. Efficacy was assessed by an external, independent radiologist. The one-sample multiple testing procedure of Fleming was applied at the predetermined recruitment stages of 20 and 40 assessable patients.Sixty-seven patients were enrolled. Five patients were not assessable for tumor response. The response rate was 13.8% (95% CI, 6.5% to 24.7%). The median survival was 10.8 months (95% CI, 7.8 to 12.0 months). The most common adverse events were anemia, neutropenia, fatigue, constipation, and nausea. Of grade 3 and 4 toxicities, neutropenia and constipation were the most common (45% and 9% of patients, respectively).Vinflunine can be delivered with high-dose intensity in patients with MPM. The response rate and median survival are encouraging for a single agent. These data suggest that vinflunine should be further evaluated in the management of MPM.