Mark R. Cullen

Bio: Mark R. Cullen is an academic researcher from Stanford University. The author has contributed to research in topics: Population & Occupational safety and health. The author has an hindex of 60, co-authored 331 publications receiving 17473 citations. Previous affiliations of Mark R. Cullen include University of Pennsylvania & University of Washington.

Effects of a combination of beta carotene and vitamin a on lung cancer and cardiovascular disease

Abstract: Background Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial — the Beta-Carotene and Retinol Efficacy Trial — involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. Results A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P = 0.02), as compared with the placebo group. There were no statistically significant ...

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

Occupational and environmental medicine. Meeting the growing need for clinical services

Abstract: ENVIRONMENTAL and occupational diseases encompass a wide range of human illness and are important causes of disability and death in modern American society.1 , 2 They include lung cancer and mesothelioma in persons exposed to asbestos, leukemia in persons exposed to benzene, asthma and chronic bronchitis in persons exposed to organic dusts, lung cancer in persons exposed to radon, chronic disorders of the nervous system in workers exposed to solvents, kidney failure and hypertension in persons chronically exposed to lead, heart disease in persons exposed to carbon disulfide, impairment of reproductive function in persons exposed to certain solvents and pesticides, and chronic . . .

A Chitinase-like Protein in the Lung and Circulation of Patients with Severe Asthma

Abstract: Background The evolutionarily conserved 18-glycosyl-hydrolase family contains true chitinases and chitinase-like proteins that lack enzymatic activity. Acidic mammalian chitinase has recently been associated with animal models of asthma. The related chitinase-like protein, YKL-40 (also called human cartilage glycoprotein 39 [HCgp-39] and chitinase 3–like 1), can be readily measured in the serum. However, its relationship to asthma has not been evaluated. Methods We quantified serum YKL-40 levels in three cohorts of patients with asthma — one recruited from the patient population at Yale University, one from the University of Paris, and one from the University of Wisconsin — as well as in controls from the surrounding communities. In the Paris cohort, immunohistochemical analysis and morphometric quantitation were used to evaluate the locus of expression of YKL-40 in the lung. The clinical characteristics of the patients with high serum or lung YKL-40 levels were also evaluated. Results Serum YKL-40 levels...

Atherosclerosis — An Inflammatory Disease

Abstract: Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principal risk factors for atherosclerosis,1 the process of atherogenesis has been considered by many to consist largely of the accumulation of lipids within the artery wall; however, it is much more than that. Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations,2,3 cardiovascular disease continues to be the principal cause of death in the United States, Europe, and much of Asia.4,5 In fact, the lesions of atherosclerosis represent . . .

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans

Abstract: Viral hepatitis in all its forms is a major public health problem throughout the world, affecting several hundreds of millions of people. Viral hepatitis is a cause of considerable morbidity and mortality both from acute infection and chronic sequelae which include, in the case of hepatitis B, C and D, chronic active hepatitis and cirrhosis. Hepatocellular carcinoma, which is one of the 10 commonest cancers worldwide, is closely associated with hepatitis B and, at least in some regions of the world, with hepatitis C virus. This timely monograph is a distillation of knowledge of hepatitis B, C and D, based on a review of 1000 studies by a small group of scientists. (It is interesting to note in passing that some 5000 papers on viral hepatitis are published annually in the world literature.) The epidemiological, clinical and experimental data on the association between infection with hepatitis B virus and primary liver cancer in humans are reviewed in a readable and succinct format. The available information on hepatitis C and progression to chronic infection is also evaluated and it is concluded (perhaps a little prematurely) that hepatitis C virus is carcinogenic. However, it is concluded that hepatitis D virus, an unusual virus with a number of similarities to certain plant viral satellites and viroids, cannot be classified as a human carcinogen. There are some minor criticisms: there are few illustrations and some complex tabulations (for example, Table 6) and no subject index. A cumulative cross index to IARC Monographs is of little value and occupies nearly 30 pages. This small volume is a useful addition to the overwhelming literature on viral hepatitis, and the presentation is similar to the excellent World Health Organisation Technical Reports series on the subject published in the past. It is strongly recommended as a readable up-to-date summary of a complex subject; and at a cost of 65 Sw.fr (approximately £34) is excellent value. A J ZUCKERMAN