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Biomedical subjects

G Virella

Publications and source records attributed to G Virella.

At least 37 records · Page 2Linked to original sources
PubMed1996

Modified lipoproteins, cytokines and macrovascular disease in non-insulin-dependent diabetes mellitus.

The processes of glycation and oxidation play a significant role in the acceleration of atherosclerosis in diabetes mellitus. Glycation is thought not only to increase the susceptibility of low-density lipoprotein (LDL) to oxidation but also to enhance the propensity of vessel wall structural proteins to bind extravasated plasma proteins, including LDL, and thus to contribute to a more marked oxidative modification of LDL. Glycated and oxidized lipoproteins induce cholesteryl ester accumulation in human macrophages and may promote platelet and endothelial cell dysfunction. Furthermore, these modified lipoproteins have the ability to trigger an autoimmune response that leads to the formation of autoantibodies and subsequently to the formation of immune complexes containing LDL. Both the modified lipoproteins and the immune complexes formed with autoantibodies reactive with modified lipoproteins may be responsible for several alternative and not mutually exclusive pathways leading to foam cell formation, macrophage activation and endothelial cell damage and may thus be of potential significance in initiating and/or contributing to the acceleration of the development of atherosclerosis. In this review we discuss how modified LDL affects lipoprotein metabolism, how immune complexes containing LDL induce the transformation of macrophages into foam cells and promote macrophage activation leading to the release of cytokines and thus initiating a sequence of events leading to endothelial cell damage and to the recruitment and activation of leucocytes. We also summarize our work showing that macrophage activation by LDL containing immune complexes leads to a paradoxical increase in LDL-receptor expression thus further impairing cholesterol homeostasis and enhancing the development of atheromatous lesions.

Arteriosclerosis↗
PubMed1995

A population-based serologic survey of immunity to tetanus in the United States.

BACKGROUND: Vaccination rates are frequently considered a surrogate measure of protection. To provide more accurate estimates, serum levels of antibody against tetanus were measured as part of the third National Health and Nutrition Examination Survey (NHANES III), which studied a representative sample of the civilian, noninstitutionalized population of the United States. METHODS: We measured tetanus antitoxin using a solid-phase enzyme immunoassay in serum samples from 10,618 persons six years of age and older who were examined during phase 1 of NHANES III in 1988 to 1991. RESULTS: Overall, 69.7 percent of Americans six years of age and older had protective levels of tetanus antibodies (> 0.15 IU per milliliter). The rate decreased from 87.7 percent among those 6 to 11 years of age to 27.8 percent among those 70 years of age or older. Among children 6 to 16 years of age, 82.2 percent had protective levels of tetanus antibodies, with little variation according to race or ethnicity. More men than women were immune (79.0 percent vs. 62.4 percent). Mexican Americans had a significantly lower rate of immunity (57.9 percent, P < 0.05) than either non-Hispanic whites (72.7 percent) or non-Hispanic blacks (68.1 percent). Those with a history of military service, higher levels of education, or incomes above the poverty level were more likely to have protective antibody levels. Although the prevalence of immunity declined rapidly starting at the age of 40 years, most of the 107 cases of tetanus (with 20 deaths) reported in 1989 and 1990 occurred in persons 60 years of age or older. CONCLUSIONS: Despite the fact that effective vaccines against tetanus have been available since the 1940s, many Americans do not have immunity to tetanus, and the rates are lowest among the elderly. There is an excellent correlation between vaccination rates (96 percent) and immunity (96 percent) among six-year-olds. However, antibody levels decline over time, and one fifth of older children (10 to 16 years of age) do not have protective antibody levels.

Adolescent↗
PubMed1995

Immunological function in post-traumatic splenosis.

A 28-year-old male medical student underwent splenectomy at 8 years of age due to traumatic rupture of the spleen sustained in a motor vehicle accident. Eighteen years later the patient had major abdominal surgery performed for an unrelated condition and, at the time of surgery, over 100 splenic nodules were found embedded throughout the patient's omentum, small bowel, and mesentery. An extensive study of immunological functions was carried out during the following 2 years. Through the course of this investigation, it was determined that the patient's peripheral blood smear lacked Howell-Jolly bodies and deformed or damaged erythrocytes, indicating that the splenotic tissue had the capacity to remove intranuclear inclusions from circulating red cells and to phagocytose old erythrocytes. The patient's levels of complement, serum immunoglobulins and the numbers of circulating T and B lymphocytes, helper T cells, and cytotoxic/suppressor T cells all were within the normal range. The response to Streptococcus pneumoniae polysaccharides was also normal, with increased levels of specific antibodies to all serotypes included in the vaccine 4 months after immunization. Finally, histological examination of his biopsied splenotic nodules revealed tissue that was indistinguishable from normal spleen.

Adult↗
PubMed1995

Activation of human monocyte-derived macrophages by immune complexes containing low-density lipoprotein.

Human monocyte-derived macrophages are transformed into foam cells upon incubation with immune complexes containing low-density lipoprotein (LDL-IC), which are internalized predominantly through Fc gamma receptor-mediated phagocytosis. We investigated whether the FcR gamma-mediated ingestion of LDL-IC is associated with functional and metabolic activation of the ingesting cells. As end points we used the assay of released interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) and the reduction of nitroblue tetrazolium, which measures the respiratory burst. LDL-IC, added to the macrophages in concentrations known to induce intracellular accumulation of cholesterol esters and foam cell transformation, stimulated both the cytokine release and the respiratory burst more efficiently than control immune complexes. Time course studies of cytokine release and mRNA expression suggest that the synthesis and release of these two cytokines is under independent control. TNF alpha was released almost immediately after addition of LDL-IC to the macrophages, coinciding with increased early expression of TNF alpha mRNA, detectable 30 min after stimulation. In contrast, IL-1 beta was only increased in stimulated cell supernatants after 8 hr, and the onset of expression of IL-1 beta mRNA was also delayed in comparison to that of TNF alpha mRNA. We noted wide variations in the amounts of TNF alpha released by monocyte-derived macrophages from different donors. We also found that those macrophages which released higher levels of TNF alpha also took up higher amounts of 125I-labeled LDL, suggesting that the expression of LDL receptors by LDL-IC-stimulated macrophages is somehow linked to the degree of activation of these cells. Experiments using the measurement of the oxidative burst as end point corroborated that LDL-IC cause a general activation of macrophage functions. In conclusion, human macrophages are efficiently activated by LDL-IC, as reflected by the release of IL-1 beta and TNF alpha and by the release of oxygen active radicals. Thus, the presentation of LDL-IC to human macrophages induces a variety of metabolic and functional changes which are likely to contribute, directly or indirectly, to endothelial damage and progression of the atheromatous lesion.

Antigen-Antibody Complex↗
PubMed1994

Atherosclerosis and autoimmunity.

The possible involvement of immunological mechanisms in the pathogenesis of atherosclerosis has been suggested intermittently since the early 1970s. Both humoral and cellular mechanisms have been proposed to participate in the onset and/or progression of atheromatous lesions, but the theories postulating the involvement of autoantibodies and immune complexes have met with considerable experimental support. Modified lipoproteins, particularly different forms of oxidized LDL, have been reported to elicit humoral immune responses in both experimental animals and humans. Oxidized LDL has been demonstrated in atheromatous lesions, anti-oxidized LDL antibodies have been detected in circulation and in atheromatous plaques, and immune complexes formed with LDL and anti-LDL have been isolated from the serum of patients with manifestations of atherosclerosis. In addition, in vitro-formed LDL-IC and IC isolated from patients have been demonstrated to cause intracellular accumulation of cholesteryl esters (CE) in human macrophages and fibroblasts. The accumulation of CE in macrophages exposed to LDL-IC is unique to this type of IC and is associated with a paradoxical overexpression of the native LDL receptor and with increase synthesis and release of interleukin 1 and TNF-alpha. The release of these cytokines in the subendothelial space may have a significant role in promoting the interaction of endothelial cells with mononuclear cells, causing endothelial cell damage directly or indirectly, and also in inducing smooth muscle cell proliferation. Thus, several lines of evidence suggest that humoral autoimmunity may play a significant role in the pathogenesis of atherosclerosis.

Animals↗
PubMed1993

Anti-oxidized low-density lipoprotein antibodies in patients with coronary heart disease and normal healthy volunteers.

We have developed a solid-phase enzyme immunoassay for anti-oxidized low-density lipoprotein antibodies. Most sera showed some degree of non-specific binding to plates coated with oxidized low-density lipoprotein and the autoantibodies to oxidized low-density lipoprotein often appeared to have a relatively low affinity. To differentiate between specific and non-specific binding each sample was tested untreated and after absorption with oxidized low-density lipoprotein. The optical densities obtained with dilutions of the absorbed sample were considered to reflect non-specific binding and were subtracted from values obtained with identical dilutions of the unabsorbed sample, to yield corrected values from which the concentrations of anti-oxidized low-density lipoprotein antibody were calculated. Similar absorptions with native low-density lipoprotein and oxidized human serum albumin failed to induce a significant reduction in binding to immobilized oxidized low-density lipoprotein proving that the antibodies measured by this assay are primarily specific for oxidized low-density lipoprotein. We studied sera from two groups of individuals: (1) 33 subjects submitted to coronary angiography and split into two subgroups depending on the degree of coronary stenosis and (2) 64 healthy individuals also split into two subgroups according to lipid levels. Anti-oxidized low-density lipoprotein antibodies were detected both in patients and healthy individuals. Higher levels were detected in patients with moderate coronary disease and hyperlipemic healthy individuals, but the differences between patients and healthy volunteers or between their respective subgroups did not reach statistical significance. Our results suggest that autoantibodies to oxidized low-density lipoprotein are relatively frequent in both symptomatic and asymptomatic individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗