tbuckley/cabot-search huggingface dataset:
CD28/B7 SYSTEM OF T CELL COSTIMULATION
Authors: Deborah J. Lenschow, Theresa L. Walunas, Jeffrey A. Bluestone
Journal: Annual Review of Immunology (1996)

▪ Abstract T cells play a central role in the initiation and regulation of the immune response to antigen. Both the engagement of the TCR with MHC/Ag and a second signal are needed for the complete activation of the T cell. The CD28/B7 receptor/ligand system is one of the dominant costimulatory pathways. Interruption of this signaling pathway with CD28 antagonists not only results in the suppression of the immune response, but in some cases induces antigen-specific tolerance. However, the CD28/B7 system is increasingly complex due to the identification of multiple receptors and ligands with positive and negative signaling activities. This review summarizes the state of CD28/B7 immunobiology both in vitro and in vivo; summarizes the many experiments that have led to our current understanding of the participants in this complex receptor/ligand system; and illustrates the current models for CD28/B7-mediated T cell and B cell regulation. It is our hope and expectation that this review will provoke additional research that will unravel this important, yet complex, signaling pathway.
Characteristics and Outcomes in Adult Patients Receiving Mechanical Ventilation&lt;SUBTITLE&gt;A 28-Day International Study&lt;/SUBTITLE&gt;
Authors: Andrés Esteban, Antonio Anzueto, Fernando Frutos, Inmaculada Alía, Laurent Brochard, Thomas E. Stewart, Salvador Benito, Scott K. Epstein, Carlos Apezteguía, Peter Nightingale, Alejandro C. Arroliga, Martin J. Tobin
Journal: JAMA (2002)

The outcome of patients receiving mechanical ventilation for particular indications has been studied, but the outcome in a large number of unselected, heterogeneous patients has not been reported.To determine the survival of patients receiving mechanical ventilation and the relative importance of factors influencing survival.Prospective cohort of consecutive adult patients admitted to 361 intensive care units who received mechanical ventilation for more than 12 hours between March 1, 1998, and March 31, 1998. Data were collected on each patient at initiation of mechanical ventilation and daily throughout the course of mechanical ventilation for up to 28 days.All-cause mortality during intensive care unit stay.Of the 15 757 patients admitted, a total of 5183 (33%) received mechanical ventilation for a mean (SD) duration of 5.9 (7.2) days. The mean (SD) length of stay in the intensive care unit was 11.2 (13.7) days. Overall mortality rate in the intensive care unit was 30.7% (1590 patients) for the entire population, 52% (120) in patients who received ventilation because of acute respiratory distress syndrome, and 22% (115) in patients who received ventilation for an exacerbation of chronic obstructive pulmonary disease. Survival of unselected patients receiving mechanical ventilation for more than 12 hours was 69%. The main conditions independently associated with increased mortality were (1) factors present at the start of mechanical ventilation (odds ratio [OR], 2.98; 95% confidence interval [CI], 2.44-3.63; P<.001 for coma), (2) factors related to patient management (OR, 3.67; 95% CI, 2.02-6.66; P<.001 for plateau airway pressure >35 cm H(2)O), and (3) developments occurring over the course of mechanical ventilation (OR, 8.71; 95% CI, 5.44-13.94; P<.001 for ratio of PaO(2) to fraction of inspired oxygen <100).Survival among mechanically ventilated patients depends not only on the factors present at the start of mechanical ventilation, but also on the development of complications and patient management in the intensive care unit.
Heterocyclic amine intake, smoking, cytochrome P450 1A2 and<i>N</i>-acetylation phenotypes, and risk of colorectal adenoma in a multiethnic population
Authors: Jenna Voutsinas, Lynne R Wilkens, Adrian Franke, Thomas M Vogt, Lance A Yokochi, Robert Decker, Loïc Le Marchand
Journal: Gut (2012)

<h3>Objective</h3> Heterocyclic amines (HAA) are animal carcinogens that are present in meat cooked at high temperature and in tobacco smoke. These compounds require activation by cytochrome P450 1A2 (CYP1A2) and <i>N</i>-acetyltransferase-2 (NAT2) before they can damage DNA. This study tested the hypotheses that well-done meat and cigarette smoking increase the risk of adenoma, the precursor to most colorectal cancers, especially in individuals with rapid CYP1A2 and rapid NAT2 activities. <h3>Design</h3> An endoscopy-based case–control study of adenoma was conducted among Caucasians, Japanese and native Hawaiians to test this hypothesis. The overall diet and consumption of well-done meat cooked by various high-temperature methods were assessed by interview in 1016 patients with a first adenoma and 1355 controls with a normal endoscopy. A caffeine test was used to assess CYP1A2 and NAT2 activities in 635 cases and 845 controls. Logistic regression was used to account for matching factors and potential confounders. <h3>Results</h3> Smoking was associated with an increased risk of adenoma. Weak non-significant elevated OR were observed for the main effects of HAA intakes or NAT2 activity. However, the combined effects of HAA intakes and NAT2 activity were statistically significant. Subjects in both the upper tertiles of NAT2 activity and HAA intake were at increased risk of adenoma compared with subjects in the lower tertiles of NAT2 activity and exposure (2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline intake OR 1.70, 95% CI I 1.06 to 2.75; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline intake OR 1.91, 95% CI 1.16 to 3.16; and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine intake OR 2.14, 95% CI 1.31 to 3.49). <h3>Conclusion</h3> The data suggest that rapid <i>N</i>-acetylators with high HAA intake may be at increased risk of adenoma.
Vitamin E and the Risk of Prostate Cancer
Authors: Eric A. Klein, Ian M. Thompson, Catherine M. Tangen, John J. Crowley, M. Scott Lucia, Phyllis J. Goodman, Lori M. Minasian, Leslie G. Ford, Howard L. Parnes, J. Michael Gaziano, Daniel D. Karp, Michael M. Lieber, Philip J. Walther, Laurence Klotz, J. Kellogg Parsons, Joseph L. Chin, Amy K. Darke, Scott M. Lippman, Gary E. Goodman, Frank L. Meyskens, Laurence H. Baker
Journal: JAMA (2011)

<h3>Context</h3>The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer.<h3>Objective</h3>To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men.<h3>Design, Setting, and Participants</h3>A total of 35 533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34 887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011.<h3>Interventions</h3>Oral selenium (200 μg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years.<h3>Main Outcome Measures</h3>Prostate cancer incidence.<h3>Results</h3>This report includes 54 464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination.<h3>Conclusion</h3>Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.<h3>Trial Registration</h3>Clinicaltrials.gov Identifier: NCT00006392
Inhibition of Type 1 Cytokine–mediated Inflammation by a Soluble CD30 Homologue Encoded by Ectromelia (Mousepox) Virus
Authors: Margarida Saraiva, Philip Smith, Padraic G. Fallon, Antonio Alcami
Journal: The Journal of Experimental Medicine (2002)

CD30 is up-regulated in several human diseases and viral infections but its role in immune regulation is poorly understood. Here, we report the expression of a functional soluble CD30 homologue, viral CD30 (vCD30), encoded by ectromelia (mousepox) virus, a poxvirus that causes a severe disease related to human smallpox. We show that vCD30 is a 12-kD secreted protein that not only binds CD30L with high affinity and prevents its interaction with CD30, but it also induces reverse signaling in cells expressing CD30L. vCD30 blocked the generation of interferon γ–producing cells in vitro and was a potent inhibitor of T helper cell (Th)1- but not Th2-mediated inflammation in vivo. The finding of a CD30 homologue encoded by ectromelia virus suggests a role for CD30 in antiviral defense. Characterization of the immunological properties of vCD30 has uncovered a role of CD30–CD30L interactions in the generation of inflammatory responses.
Waxy Phenotype Evolution in the Allotetraploid Cereal Broomcorn Millet: Mutations at the GBSSI Locus in Their Functional and Phylogenetic Context
Authors: Harriet V. Hunt, Hannah M. Moots, Robert A. Graybosch, Huw Jones, Mary Parker, Olga Romanova, Martin K. Jones, Christopher J. Howe, Kay Trafford
Journal: Molecular Biology and Evolution (2012)

Waxy mutants, in which endosperm starch contains ∼100% amylopectin rather than the wild-type composition of ∼70% amylopectin and ∼30% amylose, occur in many domesticated cereals. The cultivation of waxy varieties is concentrated in east Asia, where there is a culinary preference for glutinous-textured foods that may have developed from ancient food processing traditions. The waxy phenotype results from mutations in the GBSSI gene, which catalyzes amylose synthesis. Broomcorn or proso millet (Panicum miliaceum L.) is one of the world's oldest cultivated cereals, which spread across Eurasia early in prehistory. Recent phylogeographic analysis has shown strong genetic structuring that likely reflects ancient expansion patterns. Broomcorn millet is highly unusual in being an allotetraploid cereal with fully waxy varieties. Previous work characterized two homeologous GBSSI loci, with multiple alleles at each, but could not determine whether both loci contributed to GBSSI function. We first tested the relative contribution of the two GBSSI loci to amylose synthesis and second tested the association between GBSSI alleles and phylogeographic structure inferred from simple sequence repeats (SSRs). We evaluated the phenotype of all known GBSSI genotypes in broomcorn millet by assaying starch composition and protein function. The results showed that the GBSSI-S locus is the major locus controlling endosperm amylose content, and the GBSSI-L locus has strongly reduced synthesis capacity. We genotyped 178 individuals from landraces from across Eurasia for the 2 GBSSI and 16 SSR loci and analyzed phylogeographic structuring and the geographic and phylogenetic distribution of GBSSI alleles. We found that GBSSI alleles have distinct spatial distributions and strong associations with particular genetic clusters defined by SSRs. The combination of alleles that results in a partially waxy phenotype does not exist in landrace populations. Our data suggest that broomcorn millet is a system in the process of becoming diploidized for the GBSSI locus responsible for grain amylose. Mutant alleles show some exchange between genetic groups, which was favored by selection for the waxy phenotype in particular regions. Partially waxy phenotypes were probably selected against—this unexpected finding shows that better understanding is needed of the human biology of this phenomenon that distinguishes cereal use in eastern and western cultures.
Influence of Immunosuppression and Immunorestoration on the Formation of Urethan-induced Lung Adenomas<xref ref-type="fn" rid="FN2">2</xref>
Authors: Nathan Trainin, Mariana Linker-Israeli
Journal: JNCI Journal of the National Cancer Institute (1970)

Inbred SWR/J and randombred Swiss mice, given injections of antilymphocytic serum (ALS) for different periods of time, received a single dose of the carcinogen urethan. These mice had, along with symptoms of immune impairment, a significantly increased incidence of urethan-induced lung adenomas, as compared with controls treated with normal rabbit serum (NRS). When neonatally thymectomized, urethan-treated SWR/J mice were implanted repeatedly with syngeneic thymuses, their immunologic competence was restored. Also, their neoplastic response was reduced, the tumor incidence in these mice being similar to that of intact animals and significantly lower than that in thymectomized controls. It appears, therefore, that a) impairment of immunologic competence is accompanied by an increase in the neoplastic response to urethan, and b) this increased susceptibility to the carcinogen could be abolished when the immunologie capacity of the mice was restored.
Hepatitis C virus drug resistance and immune-driven adaptations: Relevance to new antiviral therapy
Authors: Silvana Gaudieri, Andri Rauch, Katja Pfafferott, Eleanor Barnes, Wendy Cheng, Geoff McCaughan, Nick Shackel, Gary P. Jeffrey, Lindsay Mollison, Ross Baker, Hansjakob Furrer, Huldrych F. Günthard, Elizabeth Freitas, Isla Humphreys, Paul Klenerman, Simon Mallal, Ian James, Stuart Roberts, David Nolan, Michaela Lucas
Journal: Hepatology (2008)

Abstract The efficacy of specifically targeted anti-viral therapy for hepatitis C virus (HCV) (STAT-C), including HCV protease and polymerase inhibitors, is limited by the presence of drug-specific viral resistance mutations within the targeted proteins. Genetic diversity within these viral proteins also evolves under selective pressures provided by host human leukocyte antigen (HLA)-restricted immune responses, which may therefore influence STAT-C treatment response. Here, the prevalence of drug resistance mutations relevant to 27 developmental STAT-C drugs, and the potential for drug and immune selective pressures to intersect at sites along the HCV genome, is explored. HCV nonstructural (NS) 3 protease or NS5B polymerase sequences and HLA assignment were obtained from study populations from Australia, Switzerland, and the United Kingdom. Four hundred five treatment-naïve individuals with chronic HCV infection were considered (259 genotype 1, 146 genotype 3), of which 38.5% were coinfected with human immunodeficiency virus (HIV). We identified preexisting STAT-C drug resistance mutations in sequences from this large cohort. The frequency of the variations varied according to individual STAT-C drug and HCV genotype/subtype. Of individuals infected with subtype 1a, 21.5% exhibited genetic variation at a known drug resistance site. Furthermore, we identified areas in HCV protease and polymerase that are under both potential HLA-driven pressure and therapy selection and identified six HLA-associated polymorphisms ( P ≤ 0.05) at known drug resistance sites. Conclusion: Drug and host immune responses are likely to provide powerful selection forces that shape HCV genetic diversity and replication dynamics. Consideration of HCV viral adaptation in terms of drug resistance as well as host “immune resistance” in the STAT-C treatment era could provide important information toward an optimized and individualized therapy for chronic hepatitis C. (Hepatology 2009.)
Non-invasive ventilation in octuagenarians out of the intensive care unit: Tolerability, efficacy and safety results
Authors: Anna Zito, Livio Cortese, Simone Scarlata, Alice Laudisio, Claudio Pedone, Raffaele Antonelli Incalzi
Journal: European Respiratory Journal (2013)

Non-Invasive Ventilation (NIV) is an appealing option in older patients in whom endotracheal intubation may not provide long-term benefits.The evidence on its tolerability and efficacy in very old people,however,is limited to sub-intensive care and respiratory units.

Objective: to evaluate the effect of NIV in a hospitalized population of 17 patients (9 female),mean age of 88.5 years (range:84 to 100,SD 5.1)with acute, hypercapnic respiratory failure with or without respiratory acidosis admitted to a geriatric acute care ward with experience in non-invasive mechanical ventilation.

Methods: inclusion criteria were: PaO2/FiO2 50 mmHg, no indication to invasive mechanical ventilation for age, malignancies or severe comorbidies. Patients were evaluated by blood gas analysis at the beginning of NIV (T0), after one hour of ventilation (T1) and at discharge (T2). Results were analyzed by paired T-test.

Results: Mean blood gas analysis parameters at T0 were: pH 7.35(SD 0.09); PaO2 53 mmHg(SD 14.8);PaCO2 65.4 mmHg(SD 15.1); the mean PaO2/FiO2 ratio was 210.3(SD 79.4).At the T1 evaluation all parameters were significantly improved.NIV was well tolerated.The most frequent complications were facial ulcer (6/17)and abdominal distension (1/17).Three patients died, two for non-respiratory causes.All 14 surviving patients were discharged with stable gas exchanges and continued mechanical ventilation at home or in a dedicated rehab ward.Conclusions: in the very old, NIV performed by a team of pneumologists and geriatricians is effective and well tolerated,and should be considered for patients not eligible to intensive care units.
Family and Disease Management in African-American Patients With Type 2 Diabetes
Authors: Catherine A. Chesla, Lawrence Fisher, Joseph T. Mullan, Marilyn M. Skaff, Phillip Gardiner, Kevin Chun, Richard Kanter
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this project is to specify features of family life that are associated with disease management in African Americans with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 159 African-American patients with type 2 diabetes were assessed on three domains of family life (structure/organization, world view, and emotion management) and three key dimensions of disease management (morale, management behaviors, and glucose regulation). Analyses assessed the associations of family factors with disease management. RESULTS—Multivariate tests for the main effects of three family variables were significantly related to the block of disease management variables for morale (F = 3.82; df = 12,363; P &amp;lt; 0.0001) and behavior (2.12; 9,329; P &amp;lt; 0.03). Structural togetherness in families was positively related to diabetes quality of life (DQOL)–Satisfaction (P &amp;lt; 0.01). High family coherence, a world view that life is meaningful and manageable, was positively associated with general health (P &amp;lt; 0.05) and DQOL-Impact (P &amp;lt; 0.05) and negatively associated with depressive symptoms (P &amp;lt; 0.001). Emotion management, marked by unresolved family conflict about diabetes, was related to more depressive symptoms (P &amp;lt; 0.001), lower DQOL-Satisfaction (P &amp;lt; 0.01), and lower DQOL-Impact (P &amp;lt; 0.001). No family measures were related to HbA1c levels. CONCLUSIONS—The family domain of emotion management demonstrates the strongest associations with diabetes management in African-American patients, followed by family beliefs. Patient morale is the aspect of disease management that seems most related to family context.
Psychosocial aspects of asthma in adults
Authors: B D W Harrison
Journal: Thorax (1998)

In 1903 Osler wrote: “All writers agree that there is, in a majority of cases of bronchial asthma, a strong neurotic element. Many regard it as a neurosis”.1 In 1966 the authors of a popular general medical textbook included the following statement: “Psychological influences play some part in nearly every asthmatic and quite often they appear to be mainly responsible, if not in starting the asthma, at least in maintaining it. Anxieties of various kinds, a sense of frustration, or frequently discord and an atmosphere of tension in the home, often underlie the tension in the bronchi. Treatment is not likely to be satisfactory unless these influences are appreciated and the patient handled with sympathetic understanding, tact and firmness, and the difficulties eased as much as possible”.2 

In 1972 inhaled steroids became available and this ushered in the modern era of asthma management with the emphasis on anti-inflammatory treatment for what is essentially an inflammatory disease of the bronchi and bronchioles. The introduction of much more effective treatment for asthma has been associated with diminished interest in psychological or psychosocial aspects of asthma, to the extent that they are now often ignored or patients, doctors, and nurses pay no more than lip service to them.

In the recent edition of the major British book on respiratory medicine 190 pages are devoted to asthma and there are references to psychological or psychosocial aspects in children and adults on only five.3 In an 860 page international manual on asthma there were references to psychological or psychosocial factors on only 11 pages.4 In a recent excellent publication for nurses on asthma management with over 100 contributors there is no chapter on the importance of adverse psychological or social factors.5 

However, there are striking similarities between patients recognised as …