Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction.
TL;DR: Investigation for antibodies to a novel type of Chlamydia sp, TWAR, and to chlamydial lipopolysaccharide (LPS) group antigen found they could be a factor in the pathogenesis of cardiovascular diseases.
About: This article is published in The Lancet.The article was published on 1988-10-29. It has received 1981 citations till now. The article focuses on the topics: Myocardial infarction & Seroconversion.
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TL;DR: The evidence is recounted that atherosclerosis, the main cause of CAD, is an inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate, propagate, and activate lesions in the arterial tree.
Abstract: ecent research has shown that inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Immune cells dominate early atherosclerotic lesions, their effector molecules accelerate progression of the lesions, and activation of inflammation can elicit acute coronary syndromes. This review highlights the role of inflammation in the pathogenesis of atherosclerotic CAD. It will recount the evidence that atherosclerosis, the main cause of CAD, is an inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate, propagate, and activate lesions in the arterial tree. A decade ago, the treatment of hypercholesterolemia and hypertension was expected to eliminate CAD by the end of the 20th century. Lately, however, that optimistic prediction has needed revision. Cardiovascular diseases are expected to be the main cause of death globally within the next 15 years owing to a rapidly increasing prevalence in developing countries and eastern Europe and the rising incidence of obesity and diabetes in the Western world. 1 Cardiovascular diseases cause 38 percent of all deaths in North America and are the most common cause of death in European men under 65 years of age and the second most common cause in women. These facts force us to revisit cardiovascular disease and consider new strategies for prediction, prevention, and treatment.
7,551 citations
TL;DR: Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
Abstract: Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine—choline, trimethylamine N-oxide (TMAO) and betaine—were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
4,107 citations
Cites background or result from "Serological evidence of an associat..."
...Collectively, these results indicate that: (1) hepatic expression levels of multiple Fmo genes are linked to plasma TMAO levels in mice; (2) hepatic expression levels of multiple Fmo genes are associated with both the extent of aortic atherosclerosis and HDL cholesterol levels in mice; (3) hepatic expression levels of FMO3 indicate an association with plasma TMAO levels in humans; and (4) a genetic locus containing the Fmo gene cluster on chromosome 1 in mice has a strong effect on atherosclerosis....
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...(4) Confirm clinical prognostic utility in independent prospective cohort (N = 1,876) Validation Cohort 25 cases (3 yr MI, CVA, death) versus 25 age/gender-matched controls (2)...
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TL;DR: This document is an attempt to provide guidelines for prevention and management of complications, based on a workshop of selected experts, and a comprehensive review of the literature, that emphasize the importance of specialist training, disinfection, drainage, and collaboration with surgical colleagues.
2,513 citations
TL;DR: Based on the current knowledge of the role of cytokines in atherosclerosis, some novel therapeutic strategies to combat this disease are proposed and the potential of circulating cytokine levels as biomarkers of coronary artery disease is discussed.
Abstract: Atherosclerosis is a chronic disease of the arterial wall where both innate and adaptive immunoinflammatory mechanisms are involved. Inflammation is central at all stages of atherosclerosis. It is implicated in the formation of early fatty streaks, when the endothelium is activated and expresses chemokines and adhesion molecules leading to monocyte/lymphocyte recruitment and infiltration into the subendothelium. It also acts at the onset of adverse clinical vascular events, when activated cells within the plaque secrete matrix proteases that degrade extracellular matrix proteins and weaken the fibrous cap, leading to rupture and thrombus formation. Cells involved in the atherosclerotic process secrete and are activated by soluble factors, known as cytokines. Important recent advances in the comprehension of the mechanisms of atherosclerosis provided evidence that the immunoinflammatory response in atherosclerosis is modulated by regulatory pathways, in which the two anti-inflammatory cytokines interleukin-10 and transforming growth factor-beta play a critical role. The purpose of this review is to bring together the current information concerning the role of cytokines in the development, progression, and complications of atherosclerosis. Specific emphasis is placed on the contribution of pro- and anti-inflammatory cytokines to pathogenic (innate and adaptive) and regulatory immunity in the context of atherosclerosis. Based on our current knowledge of the role of cytokines in atherosclerosis, we propose some novel therapeutic strategies to combat this disease. In addition, we discuss the potential of circulating cytokine levels as biomarkers of coronary artery disease.
1,587 citations
TL;DR: A comparison study of the effects of calcification, bone resorption, and other effects on bone formation and noncalcified tissues in animals and humans using a model derived from animal toxicology and human adverse events.
Abstract: I. Introduction II. Chemistry III. Effects in Vivo A. Inhibition of calcification B. Inhibition of bone resorption C. Effects on bone formation D. Effects on noncalcified tissues IV. Mechanisms of Action A. Calcification B. Bone resorption C. Other effects V. Pharmacokinetics VI. Animal Toxicology and Human Adverse Events A. Animal toxicology B. Human adverse events VII. Conclusion
1,183 citations
References
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TL;DR: In this article, a 2 1/2-year period, the authors studied 386 University of Washington students with acute respiratory disease, to determine whether a Chlamydia psittaci strain, here designated TWAR, is an important respiratory pathogen.
Abstract: During a 2 1/2-year period, we studied 386 University of Washington students with acute respiratory disease, to determine whether a Chlamydia psittaci strain, here designated TWAR, is an important respiratory pathogen. Serologic evidence of recent TWAR infection was found in 13 students, and the organism was isolated from 8 of these. TWAR infection occurred in 12 percent of the students who had pneumonia (9 of 76), 5 percent of those with bronchitis (3 of 63), and 1 percent of those with pharyngitis (1 of 150). The TWAR infections occurred throughout the study period. Pharyngitis, often accompanied by laryngitis, was a common first symptom. Clinically, the infections resembled those with Myco-plasma pneumoniae; therefore, the patients were given courses of erythromycin used for the treatment of M. pneumoniae infections. This therapy proved to be inadequate. The limited data available suggest that the TWAR strain is a "human" C. psittaci that is spread from human to human, without a bird or animal host.
705 citations
TL;DR: Terminology for the morphologically simiilar psittacosis, lymphogranuloma venereum (LGV), trachoma organisms has been fused and terminology and tentatively grouped TRIC organisms and other species C. tra chomatis strains are developed.
533 citations
TL;DR: Microimmunofluorescence antibody tests suggest that the etiologic agent is closely related or identical to TW-183, an unusual strain of Chlamydia psittaci isolated from the eye of a child in Taiwan.
Abstract: An epidemic of mild pneumonia was discovered during a chest radiographic survey of adolescents and young adults in two communities 110 kilometers apart in northern Finland. Antibodies to chlamydial antigens were found in 32 of 34 persons with pneumonitis. Microimmunofluorescence antibody tests suggest that the etiologic agent is closely related or identical to TW-183, an unusual strain of Chlamydia psittaci isolated from the eye of a child in Taiwan. The point prevalence of pneumonitis with antibody to TW-183 in school children at the time of the survey was high- 15 and 19 patients per 1,000 students in the two communities. There was no evidence of avian transmission in the epidemic.
274 citations
TL;DR: Four epidemics of pneumonia in military trainees in Finland have been shown, by microimmunofluorescence serology, to have been caused by TWAR, a recently described, unique Chlamydia organism.
Abstract: Four epidemics of pneumonia in military trainees in Finland have been shown, by microimmunofluorescence serology, to have been caused by TWAR, a recently described, unique Chlamydia organism. The epidemics occurred in four different garrisons from 1957 to 1985. Each lasted approximately six months, and epidemics occurred during all seasons of the year. The attack rate varied from 60 to 80 per 1000 men. Routine laboratory tests for respiratory agents suggested that these epidemics represented the only clusters of patients since 1970 who were positive for antibody to Chlamydia by complement fixation. From these epidemics, 62 of 70 paired sera that were positive for Chlamydia had antibody diagnostic of recent TWAR infection. Although the conscripts with pneumonia were hospitalized, the illnesses were relatively mild, and none were life threatening. Three conscripts had two episodes of TWAR pneumonia separated by three weeks to three months. Prompt treatment with tetracycline depressed the antibody response.
232 citations
TL;DR: It is concluded that the TWAR organism may cause pneumonia in older adults and persons with chronic diseases that require hospitalization.
Abstract: From November 1981 to August 1984, 301 adult patients with community-acquired pneumonia were admitted to the major referral hospital of Nova Scotia. Serologic tests done on these patients ...
221 citations