Yale University

About: Yale University is a education organization based out in New Haven, Connecticut, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 89824 authors who have published 220665 publications receiving 12834776 citations. The organization is also known as: Yale & Collegiate School.

New regulators of NF-kappaB in inflammation.

Abstract: Research on the biological function of nuclear factor-kappaB (NF-kappaB), a key mediator of inducible transcription in the immune system, has traditionally focused on its role in the initiation of innate and adaptive immune responses. These studies have largely concentrated on the mechanisms of signalling that lead to NF-kappaB activation and on the positive role of NF-kappaB in both physiological immunity and pathological inflammation. More recently, there has been growing interest in the mechanisms that directly regulate the NF-kappaB transcriptional programmes. As a result, several new NF-kappaB regulatory components have been identified and some of the known components have been assigned new roles. In this Review, we discuss these new insights into the regulation of NF-kappaB.

Prevention of graft versus host disease by inactivation of host antigen-presenting cells.

Abstract: Graft versus host disease, an alloimmune attack on host tissues mounted by donor T cells, is the most important toxicity of allogeneic bone marrow transplantation. The mechanism by which allogeneic T cells are initially stimulated is unknown. In a murine allogeneic bone marrow transplantation model it was found that, despite the presence of numerous donor antigen-presenting cells, only host-derived antigen-presenting cells initiated graft versus host disease. Thus, strategies for preventing graft versus host disease could be developed that are based on inactivating host antigen-presenting cells. Such strategies could expand the safety and application of allogeneic bone marrow transplantation in treatment of common genetic and neoplastic diseases.

Risk Factors for Lung Cancer and for Intervention Effects in CARET, the Beta-Carotene and Retinol Efficacy Trial

Abstract: Risk Factors for Lung Cancer and for Intervention Effects in CARET, the Beta-Carotene and Retinol Efficacy Trial Gilbert S. Omenn, Gary E. Goodman, Mark D. Thornquist, John Balmes, Mark R. Cullen, Andrew Glass, James P. Keogh, Frank L. Meyskens, Jr., Barbara Valanis, James H. Williams, Jr., Scott Barnhart, Martin G. Cherniack, Carl Andrew Brodkin, Samuel Hammar* Background: Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in (3-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an al- cohol chemical form of vitamin A), and people having higher serum p-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg (3-carotene and 25 000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18 314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg P-carotene and 25 000 IU retinyl palmitate). Promptly after the January 18,1996, announcement that the CARET active in- tervention had been stopped, we published preliminary find- ings from CARET regarding cancer, heart disease, and total mortality. Purpose: We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the interven- tion. Methods: CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for p-carotene con- centration. An Endpoints Review Committee evaluated end- point reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were es- timated by use of Cox regression models; tests were per- formed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 1550 ARTICLES a value, and all P values were derived from two-sided statis- tical tests. Results: According to CARET'S pre-specified analysis, there was an RR of 136 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associa- tions of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol in- take has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum p-carotene concentrations. Conclusions: CARET participants receiving the combination of P-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for p-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Preven- tion Study in 29 133 male smokers in Finland. Implications: Individuals at high risk of developing lung cancer, i.e., cur- rent smokers and asbestos-exposed workers, should be dis- couraged from taking supplemental P-carotene (and the combination of p-carotene with vitamin A). Safety and ef- ficacy should be demonstrated before recommending use of vitamin supplements in any population. [J Natl Cancer Inst * Affiliations of authors: G. S. Omenn, S. Bamhart, C A. Brodkin, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, and Departments of Environmental Health and Medicine, University of Washington, Seattle; G. E. Goodman, Division of Public Health Sciences. Fred Hutchinson Cancer Research Center, Departments of Environmental Health and Medicine, University of Washington, and Swedish Hospital Tumor Institute, Seattle; M. D. Thomquist, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, J. Balmes, Department of Medicine, University of California at San Francisco; M. R. Cullen, M. G. Chemiack, Department of Medicine, Yale University, New Haven, CT; A. Glass, B. Valanis, Kaiser Permanente Center for Health Research, Portland, OR; J. P. Keogh, Department of Medicine, University of Maryland, Baltimore; F. L Meyskens, Jr., J. H. Williams, Jr., Department of Medicine and Cancer Center, University of California/Irvine, Orange; S. Hammar, Departments of Environmen- tal Health and Pathology, University of Washington. Correspondence to: Gilbert S. Omenn, M.D., Ph.D., Fred Hutchinson Cancer Research Center, 1124 Columbia St., MP-859, Seattle, WA 98104. See Notes section following References. Journal of the National Cancer Institute, Vol. 88, No. 21, November 6, 1996