Framingham score and LV mass predict events in young adults: CARDIA study.

BACKGROUND: Framingham risk score (FRS) underestimates risk in young adults. Left ventricular mass (LVM) relates to cardiovascular disease (CVD), with unclear value in youth. In a young biracial cohort, we investigate how FRS predicts CVD over 20 years and the incremental value of LVM. We also explore the predictive ability of different cut-points for hypertrophy. METHODS: We assessed FRS and echocardiography-derived LVM (indexed by body surface area or height2.7) from 3980 African-American and white Coronary Artery Risk Development in Young Adults (CARDIA) participants (1990-1991); and followed over 20 years for a combined endpoint: cardiovascular death; nonfatal myocardial infarction, heart failure, cerebrovascular disease, and peripheral artery disease. We assessed the predictive ability of FRS for CVD and also calibration, discrimination, and net reclassification improvement for adding LVM to FRS. RESULTS: Mean age was 30±4 years, 46% males, and 52% white. Event incidence (n=118) across FRS groups was, respectively, 1.3%, 5.4%, and 23.1% (p<0.001); and was 1.4%, 1.3%, 3.7%, and 5.4% (p<0.001) across quartiles of LVM (cut-points 117 g, 144 g, and 176 g). LVM predicted CVD independently of FRS, with the best performance in normal weight participants. Adding LVM to FRS modestly increased discrimination and had a statistically significant reclassification. The 85th percentile (≥116 g/m2 for men; ≥96 g/m2 for women) showed event prediction more robust than currently recommended cut-points for hypertrophy. CONCLUSION: In a biracial cohort of young adults, FRS and LVM are helpful independent predictors of CVD. LVM can modestly improve discrimination and reclassify participants beyond FRS. Currently recommended cut-points for hypertrophy may be too high for young adults.

Amino acid, fatty acid, and carbohydrate content of Artocarpus altilis (breadfruit).

A study is conducted to determine the amino acid, fatty acid, and carbohydrate content of breadfruit using high-performance liquid chromatography (HPLC) and gas chromatography (GC). An HPLC method is used for the determination of amino acids and fatty acids in breadfruit. Representative amino acid samples are derivatized with phenylisothiocianate and the resulting phenylthiocarbamyl derivatives are separated on a reversed-phase column by gradient elution with a 0.05M ammonium acetate buffer and 0.01M ammonium acetate in acetonitrile-methanol-water (44:10:46, v/v). Representative fatty acid samples are derivatized with phenacyl bromide and the resulting fatty acid phenacyl esters are separated on a reversed-phase column by gradient elution with acetonitrile and water. Amino acid and fatty acid derivatives are detected by ultraviolet detection at 254 nm. The analysis of the carbohydrates in breadfruit employs a GC method. Carbohydrates are derivatized using trimethylchlorosilane and hexamethyldisilazane to form trimethylsilyl ethers. Compounds in the samples are separated by the temperature programming of a GC using nitrogen as the carrier gas. Percent recoveries of amino acids, fatty acids, and carbohydrates are 72.5%, 68.2%, and 81.4%, respectively. The starch content of the breadfruit is 15.52 g/100 g fresh weight.

Anti-gamma delta T cell antibody blocks the induction and maintenance of oral tolerance to ovalbumin in mice.

The oral administration of antigens is one of the means of inducing tolerance in adult mammals. In this report, the role of gamma delta T cells in the induction and maintenance of orally-induced tolerance to ovalbumin was investigated. The injection of a monoclonal anti-gamma delta T cell monoclonal antibody blocked the induction of oral tolerance, because the secondary immune responses to ovalbumin in these animals were comparable to the corresponding responses in ovalbumin-immunized control mice. Furthermore, depletion of gamma delta T cells either in vivo or in vitro abolished already established oral-tolerance. The fact that the state of tolerance could be adoptively transferred to naive recipients by CD3+ alpha beta- gamma delta + spleen cells from tolerant mice. These results suggest that systemic oral tolerance is induced and actively maintained by mechanisms involving gamma delta T cells.

T cell-dependent antibody response to staphylococcal enterotoxin B.

Treatment of mice with staphylococcal enterotoxin B (SEB) induces specific T-cell tolerance to this superantigen, characterized by partial deletion of V beta 8+ T cells in vivo and T cell anergy in vitro. In this study we examined the humoral response to SEB in BALB/c mice. Immunization of mice with SEB results in a detectable anti-SEB antibody response. Upon further treatment of mice with SEB, specific antibody levels increase significantly and the response is accelerated--characteristics of a secondary humoral response. The secondary antibody response is T cell dependent, can be transferred to T cell deficient mice with splenocytes and is composed mainly of IgM, IgG1 and IgG2b isotypes, suggesting that Th2 cells provide B cell help in this response. These data demonstrate that at the same time as inducing in vitro unresponsiveness, SEB primes SEB-specific T helper cells to provide help for B cells in a secondary antibody response.

Age-dependent changes in the response to staphylococcal enterotoxin B.

In the present study we investigated the response of old mice to staphylococcal enterotoxin B (SEB) immunization. Old mice were susceptible to lethal toxic shock, probably mediated by tumor necrosis factor-alpha, although lethal toxic shock was not observed in young mice. Old mice were able to produce more IL-2 and IL-4 than young mice in response to in vivo immunization with SEB. V beta 8+CD4+ T cells of old mice expanded less in vivo and were not deleted in response to SEB. However, in spite of the absence of clonal deletion, SEB was found to induce energy of SEB reactive cells in old mice, as demonstrated by reduced in vitro T cell proliferation to SEB and reduced in vitro IL-2 and IL-4 production.

The development of humoral immunological memory to a T-cell-dependent antigen requires thymic emigrant cells.

Immunological memory is embodied in the rapid and enhanced immune responsiveness to previously encountered antigens. Classically, memory would depend on the presence of small resting long-lived specific lymphocytes which, through clonal expansion after priming with antigen, would be present at higher frequencies than in naive animals. Here we report that T-cell-reconstituted athymic mice, which lack recent thymic emigrants, mount a primary response to a T-cell-dependent antigen, but do not develop memory or the capacity to produce specific anti-TNP IgG1 antibodies during the secondary immune response. On the other hand, if thymocytes are continuously provided during the secondary response, a typical secondary immune response is achieved with high levels of specific IgG1. These results lead us to propose that the development of humoral immunological memory cannot be explained solely by the long life span of primed T lymphocytes, but is rather a dynamic state dependent on the continuous presence of recent thymic emigrants and qualitative functional differences in responder T cells.

Coevolution of hosts and microorganisms: an analysis of the involvement of cytokines in host-parasite interactions.

Parasites may employ particular strategies of eluding an immune response by taking advantage of those mechanisms that normally guarantee immunological self-tolerance. Much in the way as it occurs during the establishment of self-tolerance, live pathogens may induce clonal deletion, functional inactivation (anergy) and immunosuppression. At this latter level, it appears that certain pathogens produce immunosuppressive cytokine-like mediators or provoke the host to secrete cytokines that will compromise the anti-parasite immune response. It appears that immune responses that preferentially involve T helper 1 cells (secretors of interleukin-2-and interferon-gamma) tend to be protective, whereas T helper 2 cells (secretors of IL-4, IL-5, IL-6, and IL-10), a population that antagonizes T helper cells, mediate disease susceptibility and are involved in immunopathological reactions. Cytokines produced by T helper 2 cells mediate many symptoms of infection, including eosinophilia, mastocytosis, hyperimmunoglobulinemia, and elevated IgE levels. Administration of IL-2 and IFN-gamma has beneficial effects in many infections mediated by viruses, bacteria, and protozoa. The use of live vaccinia virus might be an avenue for the treatment of or the vaccination against infection. We have found that a vaccinia virus expressing the gene for human IL-2, though attenuated, precipitates autoimmune disease in immunodeficient, athymic mice. Thus, although T helper 1 cytokines may have desired immunostimulatory properties, they also may lead to unwarranted autoaggressive responses.