Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In separate experiments, we fed 30 male and 25 female baboons a diet enriched in cholesterol and saturated fat for periods of 3.3 and 2.6 years. Using operant conditioning with water rewards, we trained the animals to puff on smoking machines in a human-like manner. Half of the animals smoked more than 40 cigarettes per day, while the remaining animals (controls) puffed air. Initially, the diet produced twofold (males) and threefold (females) elevations from baseline levels in serum cholesterol concentrations, but over the course of the experiments, the serum cholesterol decreased to 1.5 (males) and 2.0 (females) times baseline levels in both cigarette smokers and controls. Blood carbon monoxide concentration, plasma thiocyanate concentration, and urine cotinine concentration were significantly greater in smokers than in controls. Responses to smoking in males included lymphocytosis, elevated fasting blood glucose concentration, and decreased seminal vesicle weight. In females, hemoglobin and mean corpuscular hemoglobin concentrations were elevated. The extent of atherosclerosis was examined after 2.8 (males) and 1.6 (females) years of smoking. Among males, the extent of lesions in carotid arteries was significantly greater in smokers than in controls, but there were no significant differences in atherosclerosis in the aorta or the brachial, iliac-femoral, or coronary arteries. Among females, there were no significant differences in atherosclerosis between smokers and controls in any artery. These experiments show little effect of 2 to 3 years of cigarette smoke inhalation and concurrent modest elevation of blood carboxyhemoglobin on experimental atherosclerosis in the presence of moderate hyperlipidemia.
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PMID:Cigarette smoking, dietary hyperlipidemia, and experimental atherosclerosis in the baboon. 333 49

Sudden cardiac death is the leading cause of death in industrialized countries. It is most frequently due to ventricular tachyarrhythmias occurring in the presence of coronary heart disease, but mechanisms linking sudden death to coronary atherosclerosis are still unclear. In autopsy studies of sudden death patients, the incidence of acute thrombotic coronary occlusions has varied between 4 and 74%. In over 600 consecutive patients with implantable cardioverter-defibrillators, we observed that appropriate shocks for electrogram-verified ventricular tachyarrhythmias was only very rarely followed by signs of acute myocardial infarction (< 3% of cases), not supporting the coronary occlusion theory of fatal arrhythmias. Cellular hypertrophy compensating for cell loss due to ischemia, intraventricular hypertension, cardiomyopathy, and myocarditis might play a role in arrhythmogenesis as evidenced by the fact that experimental induction and regression of hypertrophy are paralleled by changes in the inducibility of ventricular tachyarrhythmias. Atherogenic hyperlipidemias are associated with a systemic inflammatory response manifested by leukocytosis (lymphocytosis) and complex upregulations of proinflammatory-prothrombotic mediators, such as platelet-activating factor, cytokines, and hemostasis factors. The diurnal regulation of these mediators parallels circadian rhythms of coronary morbidity and mortality. Some upregulated mediators have been shown to exert direct arrhythmogenic effects. The potential contribution of hyperlipidemia-associated inflammatory factors to arrhythmogenesis is important, because it opens new molecular targets for antiarrhythmic drug design.
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PMID:Sudden cardiac death: still more questions than answers. 947 68

We report a case of mantle cell lymphoma in leukemic phase, which was diagnosed by a bone marrow biopsy performed as part of a workup for chronic anemia in a patient without lymphadenopathy. The patient, a 79-year-old man with diabetes mellitus, hypertension, chronic renal failure, congestive heart failure, and atherosclerosis, presented with claudication. On admission, he also had an 8-month history of anemia, during which time he experienced a 18-kg weight loss. On presentation, the patient had normal vital signs, anemia, leukocytosis (as well as an absolute lymphocytosis), and splenomegaly; as mentioned, lymphadenopathy was absent. A bone marrow biopsy showed an increase in small to intermediate-sized, slightly irregular lymphocytes in interstitial nodules. Flow cytometric immunophenotyping of the bone marrow identified a monoclonal population of cells, representing 25% of cells within the bone marrow, with expression of CD19, CD20, immunoglobulin M/D, lambda light chain, HLA-DR, and CD5; reactions for CD10 and CD23 were absent. Based on morphologic and immunophenotypic analysis of the bone marrow, as well as morphologic review of the peripheral blood smear, a diagnosis of mantle cell lymphoma involving the bone marrow and in leukemic phase was made. Subsequent polymerase chain reaction analysis of DNA from peripheral blood identified a population of cells with the bcl-1 rearrangement. This case is unique in that the diagnosis of mantle cell lymphoma was made without lymph node or spleen analysis and the patient, although exhibiting bone marrow and peripheral blood involvement by mantle cell lymphoma at presentation, did not have lymphadenopathy.
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PMID:Leukemic phase of mantle cell lymphoma presenting as anemia: diagnosis by combining flow cytometry and cytomorphology. 982 32

T lymphocytes and monocytes/macrophages are the most abundant cells found in the atherosclerotic plaque. These cells can migrate towards the activated endothelium through the local release of chemotactic cytokines, or chemokines. Given the important role of leukocyte migration in atherosclerosis and the role of stress in mediating leukocyte trafficking, the present study examined the effects of an acute stressor on the redistribution of T cells (CD3+) and monocytes that express the chemokine receptors CCR5, CCR6, CXCR1, CXCR2, CXCR3, and CXCR4. Forty-four undergraduate students underwent a public speaking task. The acute stressor induced sympathetic cardiac activation, parasympathetic cardiac withdrawal, lymphocytosis, and monocytosis (all p<.001). Although the total number of T lymphocytes did not change, there was a selective increase in the number of circulating T cells expressing CXCR2, CXCR3, and CCR5. The ligands of these receptors are chemokines known to be secreted by activated endothelial cells. Analyses of individual differences in stress-induced responses demonstrated a positive relationship between sympathetic cardiac reactivity and mobilization of the various T cell subsets (.35<r<.56;p<.05). For the monocytes, all sub-populations increased in parallel with total monocyte numbers, with no relation to changes in sympathetic cardiac drive. These results indicate that acute stress induces a mobilization of T cells that are primed to respond to inflamed endothelium. Acute stressors may thus promote the recruitment of circulating immune cells into the sub-endothelia, and therefore accelerate atherosclerotic plaque formation and potentially contribute to the complications that follow acute stressful events. This mechanism may help explain the link between stress, reactivity, and cardiovascular disease.
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PMID:Acute stress evokes selective mobilization of T cells that differ in chemokine receptor expression: a potential pathway linking immunologic reactivity to cardiovascular disease. 1283 27

Evidence of immune stimulation has been noted in opiate dependent patients for many decades. Documented changes have included lymphadenopathy, round cell infiltration of the hepatic portal triads, diffuse peri-bronchitis, hyperglobulinaemia, lymphocytosis, monocytosis, systemic cytokine stimulation, and cytokine and chemokine activation within the neuraxis. A parallel literature describes an elevated list of chronic degenerative disease as common in such patients including neurodegenerative conditions, atherosclerosis, nephrosclerosis, hepatic fibrosis and cirrhosis, chronic obstructive and fibrotic lung disease, osteoporosis, chronic periodontitis, various cancers, hair greying, and stem cell suppression. All of these disorders are now known to have an important immunological role in their pathogenic pathways. The multisystem nature of these myriad changes strongly suggest that the ageing process itself is stimulated in these patients. The link between the immunostimulation on the one hand and the elevated and temporally advanced nature of the chronic degenerative diseases on the other appears not to have been made in the literature. Moreover as immunostimulation is also believed to be an important, potent and principal contributor to the ageing process it appears that experimental and studies of this putative link are warranted. Verification of such an hypothesis would also carry management implications for dose and duration of chronic pain and addiction treatment, pharmacotherapeutic selection, and novel treatments such as long term naltrexone implant therapy and heroin trials.
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PMID:Chronic immune stimulation as a contributing cause of chronic disease in opiate addiction including multi-system ageing. 2080 Mar 62

Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity. As atherosclerosis is a chronic inflammatory process with features of autoimmune disease, we investigated the impact of hematopoietic Bim deficiency on plaque formation and parameters of plaque stability. Bim -/- or wild type bone marrow transplanted ldlr -/- mice were fed a Western type diet (WTD) for 5 or 10 weeks, after which they were immunophenotyped and atherosclerotic lesions were analyzed. Bim -/- transplanted mice displayed splenomegaly and overt lymphocytosis. CD4+ and CD8+ T cells were more activated (increased CD69 and CD71 expression, increased interferon gamma production). B cells were elevated by 147%, with a shift towards the pro-atherogenic IgG-producing B2 cell phenotype, resulting in a doubling of anti-oxLDL IgG1 antibody titers in serum of bim -/- mice. Bim -/- mice displayed massive intraplaque accumulation of Ig complexes and of lesional T cells, although this did not translate in changes in plaque size or stability features (apoptotic cell and macrophage content). The surprising lack in plaque phenotype despite the profound pro-atherogenic immune effects may be attributable to the sharp reduction of serum cholesterol levels in WTD fed bim -/- mice.
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PMID:Leukocyte Bim deficiency does not impact atherogenesis in ldlr -/- mice, despite a pronounced induction of autoimmune inflammation. 2859 42

Environmental pollutants, such as pesticides, herbicides, additives to food and water, and electromagnetic fields threaten public health by promotion of cancer, heart disease and chronic diseases of aging. Many of these pollutants cause adverse health outcomes by effects on mitochondrial function to produce oxidative stress through loss of the active site complex for oxidative phosphorylation, thioretinaco ozonide oxygen nicotinamide adenine dinucleotide phosphate, from opening of the mitochondrial permeability transition pore. Glyphosate, fluoride, and electromagnetic fields are examples of carcinogenic pollutants that promote loss and decomposition of the active site for oxidative phosphorylation, producing mitochondrial dysfunction and oxidative stress. Ionizing radiation has long been known to be carcinogenic, and non-ionizing electromagnetic fields from microwaves, radar, cell phones and cathode ray screens are carcinogenic and produce deleterious effects on capillaries, nerve cells, blood brain barrier, embryonic and germ cells, lenses and cardiac function. Adverse health effects of electromagnetic fields include cataracts, infertility, congenital malformations, cancer, lymphocytosis, leukemia, hearing loss, blindness, retinal hemorrhages, cardiac arrhythmias, dermatitis, hair loss, depression, memory loss, premature aging, heart attacks, and weaponized mind control. The hyperhomocysteinemia, suppressed immunity, and altered oxidative metabolism observed in atherosclerosis and dementia are attributed to deficiency of adenosyl methionine which results from increased polyamine biosynthesis by pathogenic microbes that are demonstrated in atherosclerotic plaques and cerebral plaques. Thus, environmental pollutants potentially promote diseases of aging, atherosclerosis, cancer, and premature aging by production of mitochondrial dysfunction.
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PMID:Environmental Pollution, Oxidative Stress and Thioretinaco Ozonide: Effects of Glyphosate, Fluoride and Electromagnetic Fields on Mitochondrial Dysfunction in Carcinogenesis, Atherogenesis and Aging. 3258 Oct 36