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Biomedical subjects

J Hernández-Godoy

Publications and source records attributed to J Hernández-Godoy.

6 recordsLinked to original sources

Effects of nordihydroguaiaretic acid on murine antibody-dependent cellular cytotoxicity.

The purpose of this study was to analyze the effects of nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway of arachidonic acid, on antibody-dependent cellular cytotoxicity. Antibody-dependent cellular cytotoxicity mediated by murine spleen cells was significantly inhibited by concentrations of nordihydroguaiaretic acid from 10(-5) to 10(-4) M (1C50 = 2 x 10(-5) M). The inhibitory effect of nordihydroguaiaretic acid was also observed on antibody-dependent cellular cytotoxicity mediated by macrophage-depleted spleen cells as well as isolated macrophages. Nordihydroguaiaretic acid was highly effective when added at the beginning of the assay and was always present throughout the assay, but failed to inhibit the binding of effector and target cells. The inhibition produced by nordihydroguaiaretic acid could not be reversed by leukotriene B4, a 5-lipoxygenase product. These results suggest that arachidonic acid metabolites other than leukotriene B4 are released by different populations of spleen cells to positively regulate important events in the postbinding phase of murine antibody-dependent cellular cytotoxicity.

Animals↗

Seasonal variation in proliferative response and subpopulations of lymphocytes from mice housed in a constant environment.

A seasonal variation in the proliferative response to mitogens and in the proportion of splenic lymphocyte subpopulations was found in mice housed in a constant environment. The lymphoproliferative responses to T-cell and B-cell mitogens reached maximum values in autumn and summer. Identification of lymphocyte subpopulations by flow cytometry demonstrated that the proportion of T cytotoxic-suppressor (Tcs) lymphocytes was significantly higher in autumn and summer than in spring and winter. However, the proportion of B lymphocytes was significantly lower in spring than in the other three seasons, whereas the proportions of T and T helper (Th) cells did not show any seasonal variation. On the other hand, we observed a significant correlation between the level of mitogenic responsiveness and the proportion of Tcs cells, but not between the former and the proportions of B, T or Th cells. These data suggest that the seasonal variation in murine lymphoproliferative responses may depend on the cyclic changes in the proportion of Tcs lymphocytes; these changes, in turn, may be predetermined by the inherent internal biological rhythms of the animal.

Animals↗

Differential effects of the calcium ionophore A23187 and the phorbol ester PMA on lymphocyte proliferation.

The effects of the phorbol ester, phorbol-12-myristate-13-acetate (PMA), and of the calcium ionophore A23187 on DNA synthesis in murine quiescent and mitogen-stimulated lymphocytes have been examined. Neither PMA nor A23187 had any mitogen effect on their own on quiescent lymphocytes. However, stimulation of cells sequentially with A23187 and then PMA resulted in a proliferative response in proportion to the duration of the exposure to A23187, and the sustained simultaneous presence of both agents was necessary for maximum proliferation. On the other hand, while short incubations with A23187 potentiated mitogen-induced DNA synthesis, prolonged exposure inhibited it. Furthermore, on lymphocytes stimulated with two T cell mitogens, the effects of A23187 and PMA depended on the proliferation-inducing mitogens and the responsiveness level induced by them. Therefore, while PMA and short pretreatments with A23187 had no effect on high intensity mitogenic responses, low intensity responses were significantly enhanced. These results demonstrate differential effects of A23187 and PMA on DNA synthesis that should be useful in studies on the mechanisms of activation of lymphocyte proliferation.

Animals↗

Effects of lipoxygenase and cyclooxygenase inhibitors on murine antibody-dependent cellular cytotoxicity (ADCC).

The purpose of this study was to determine the effects that specific inhibition of arachidonic acid (AA) metabolism has on the antibody-dependent cellular cytotoxicity (ADCC) of murine spleen cells. The action of three inhibitors of the lipoxygenase (LO) pathway--nordihydroguaiaretic acid (NDGA), esculetin (Es), and phenanthroline (Phe)--was compared with that of three inhibitors of the cyclooxygenase (CO) pathway--indomethacin (INDO), acetyl salicylic acid (ASA), and imidazole (IMI). All the LO inhibitors suppressed ADCC function in a dose-dependent manner, but NDGA was the most potent inhibitor of this cytolytic activity. In fact, NDGA inhibited the ADCC function with 97% inhibition at 100 microM, while Phe and Es, at the same concentration, inhibited ADCC by 21% and 19%, respectively. However, CO inhibitors did not markedly affect ADCC function and only some doses of them had a slight, but significant, depressing effect (8-11% inhibition at 0.01-0.1 microM of INDO, 7% inhibition at 400 microM of ASA, and 13% inhibition at 800-1000 microM of IMI). These results suggest the LO pathway of the arachidonic acid metabolism plays an important role in regulating ADCC activity of murine spleen cells and the products of the CO pathway have little effect on ADCC lysis.

Animals↗

Autoantibodies in splenectomized patients as a consequence of abdominal trauma.

The presence of autoantibodies was examined in 100 adult patients splenectomized because of abdominal trauma and without systemic disease, and the results were compared with those observed in a healthy control group. Thirty-seven percent of the patients studied presented some type of autoantibody. Those observed were antinuclear, anti-smooth muscle and, in 1 case, anti-reticulin. Patients with antinuclear antibodies have no antibodies against native DNA, but in 5 cases, anti-Ro (SS-A) and anti-La (SS-B) antibodies were observed. Rheumatoid factors were also found, but their incidence was similar in patients and controls. The incidence of autoantibodies proved not to be related to either the period of time since splenectomy or to age of the patient; they were observed in patients many years after splenectomy and in individuals of both sexes and all ages. Although the presence of autoantibodies seemed to have no effect on our patients, all of whom were asymptomatic, it is important to be aware of this phenomenon when evaluating the laboratory results obtained from splenectomized patients.

Abdominal Injuries↗

Changes in total serum IgE concentrations after splenectomy.

In addition to allergic diseases, there are other disorders that can be accompanied by increased levels of total serum IgE. It has been demonstrated that splenectomy can alter the serum concentrations of other immunoglobulins. The aim of this study was to examine the concentrations of total IgE in the serum of patients splenectomized as a result of abdominal trauma but with no associated disease. Our results show that the average concentrations in the serum of patients were significantly higher that in the control group. Furthermore, in a large number of patients, the concentrations were above the normal limit set for the nonatopic Spanish population. These results suggest that splenectomy can alter the regulation of IgE concentrations. Since total IgE is usually determined for diagnostic purposes, it is useful to be aware of this anomaly when dealing with splenectomized patients in order to interpret correctly the laboratory analyses.

Adolescent↗