Primary osteosarcoma of the meninges.
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Biomedical subjects
Publications and source records attributed to F Bonilla.
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We herein report the case of a patient who had 4 primary tumors, 3 of which were malignant. His family had a high rate (26%) of cancer. The possible genetic factors that con produce these events are briefly discussed.
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The NZB mouse is genetically predisposed to the development of autoimmune disease that resembles the human autoimmune systemic lupus erythematosus and autoimmune hemolytic anemia, with increased titers of anti-DNA, and Coombs' autoantibodies. The various autoimmune traits are controlled separately by a limited number of genes. Genetic studies have shown that several immune loci are involved in autoimmunity: T cell abnormalities, H-2 complex and immunoglobulin genes have been implicated. In this report, we present evidence for a significant correlation of NZB V kappa 1 haplotype defined by restriction fragment length polymorphism analysis with anti-erythrocyte autoantibodies in NZB x 129/J and NZB x SM/J recombinant inbred lines.
The clinical significance of the natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) was analyzed in 83 breast cancer patients and 24 healthy control women. Similar levels of NK cytotoxic activity against K-562 target cells were found in PBMC from either untreated or surgically treated patients with local or disseminated breast cancer and from normal controls. However, a transitory and significant decrease (p less than 0.05) of the NK activity of PBMC from breast cancer patients was found during chemotherapy. But, according to quantitative flow cytometry analysis, similar percentages of phenotypically defined NK cells (CD16+, CD11b+, HNK-1+) were found in PBMC from patients, whether prior to or during chemotherapy, and healthy controls. Our results demonstrate that in breast cancer patients, the percentage of NK cells present in PBMC and their lytic activity are independent of the clinical and pathological stage of the disease.
The steroid hormone 1 alpha, 25-dihydroxyvitamin D3, calcitriol, is crucial in calcium homeostasis. Calcium plays a central role in T, B, and NK cell functions, and calcitriol is a known inhibitor of T cell proliferation and immunoglobulin production. We have analyzed here the immunoregulatory effects of calcitriol on NK cell function. We show that calcitriol specifically specifically inhibits, in a time- and dose-dependent fashion, the generation of cytotoxic activity from cultured CD16+ peripheral blood NK cells. It also suppresses, at similar molar concentrations (1-10 nM), interleukin 2 (IL-2) production by PHA-activated peripheral blood lymphocytes. Calcitriol does not interfere with the cytotoxic function of NK cells, whether fresh or generated in vitro, placing the inhibition at the level of NK cell activation. Interestingly enough, exogenous IL-2 can completely reverse the suppressive effect. These findings suggest that modulation of NK cell activation by control of the internal level of IL-2 may reflect an additional paracrine calcitriol-dependent circuit with immunoregulatory consequences.
Natural killer (NK) cells and lymphokine-activated killer (LAK) cells have been involved in immunosurveillance against tumors. A normal NK activity was observed in peripheral blood (PB) mononuclear cells (MNC) from women with breast cancer, but a very low or absent NK cytotoxicity was found in the regional lymph node (RLN) MNC. However, strong cytotoxic activity against NK-resistant and NK-sensitive target cells can be induced in RLN MNC by long-term (5-day) incubation with recombinant interleukin-2 (rIL-2). This cytotoxic inducer effect of rIL-2, not observed with recombinant interferon gamma, was dose and time-dependent and was not associated with modifications in the low number of Leu 11+ or Leu 7+ cells present in the population. Both the lack of NK activity and the generation of rIL-2-activated killer cells can be readily demonstrated in either histologically affected or unaffected RLN. These results stress the value of the immunomodulators inducing cytotoxic activity in RLN MNC of patients with tumors, and are discussed in association with their possible therapeutical role.
While there is accumulating evidence to indicate the presence of functional abnormalities in T cells from aged healthy humans, their cellular basis remains unclear. By using two-color immunofluorescence and multiparameter flow cytometry we show that (a) the number of peripheral blood antigen receptor-positive (TcR-CD3+) T cells is significantly lower in aged than in young adults; (b) the numbers of E-rosette-forming (CD2+) cells are maintained in the elderly due to a reciprocal increase in the frequency of TcR-CD3- cells, which constitute only a minor lymphocyte subpopulation in young adults, and (c) TcR-CD3-CD2+5- lymphocytes exhibit the phenotypic features of natural killer (NK) cells. By using functional assays we show the TcR-CD3-CD2+16+ lymphocytes are indeed NK cells because they are activated by and lyse NK targets. In contrast, they are unresponsive to either phytohemagglutinin or mitogenic CD2 monoclonal antibody stimulation, which in turn activates TcR-CD3+CD2+16- T cells. We conclude that the increase in TcR-CD3-CD2+ NK cells masks the T cell reduction in aged humans by normalizing CD2+ cell frequencies. However, NK cells cannot functionally substitute the thymus-derived lymphocytes they replace.
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