Biomedical subjects
M Lipscomb
Publications and source records attributed to M Lipscomb.
Why support a failing system?
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Expression of lung inducible nitric oxide synthase protein does not correlate with nitric oxide production in vivo in a pulmonary immune response against Cryptococcus neoformans.
Mice infected intratracheally with Cryptococcus neoformans (Cne) require CD4 and CD8 T cells, IFN-gamma, and M phi production of nitric oxide (NO) for effective resolution of the pulmonary infection. Differences exist among strains of mice in clearing the infection. C.B-17 mice reduced Cne lung burden at a significantly greater rate than C57BL/6 (B6) mice and resistance correlated with greater IFN-gamma production by C.B-17 lung-associated lymph node cells. We examined whether the differences observed in the ability of B6 vs C.B-17 mice to clear Cne was due to 1) numbers of inflammatory cells recruited to the lung, 2) the activation state of the recruited cells as measured by expression of inducible nitric oxide synthase (iNOS), and/or 3) the in vivo production of NO as measured by quantitating urine nitrates. The level of iNOS protein was identical in lungs from both strains of mice during Cne infection as determined by Western blot analysis of whole lung homogenates and immunocytochemistry of isolated lung macrophages. Surprisingly, in vivo studies of iNOS activity indicated that NO production in B6 mice was significantly less than that in C.B-17 mice. While single cell suspensions from lungs of either mouse strain produced identical amounts of NO, NO production by lung explants paralleled in vivo urinary nitrate excretion, suggesting that the maintenance of pulmonary architecture and cell-cell interaction was necessary for suppression of iNOS activity in B6 mice. These data strongly implicate the existence of mechanisms that regulate NO production at the level of enzyme activity during infections and have important implications for analyzing the role of iNOS during an immune response in in vivo models.
Origin and differentiation of natural killer cells. II. Functional and morphologic studies of purified NK-1.1+ cells.
Cells bearing the NK-specific marker NK-1.1 were purified from mouse spleens by utilizing a monoclonal anti-NK-1.1 antibody and cell sorting. In normal adult mice, all of the splenic NK activity against YAC-1 cells was found in the NK-1.1+ fraction, whereas NK-1.1- cells were depleted of NK activity. The NK activity of sorted NK-1.1+ cells was enriched 15- to 30-fold over unfractionated spleen cells. Light and electron microscopic studies of purified NK-1.1+ cells showed a homogeneous population of cells, each containing one to four cytoplasmic granules. Mice whose bone marrow has been destroyed by chronic exposure to 17-beta-estradiol have very low NK activity. However, spleen cells of estradiol-treated mice contained a normal frequency of NK-1.1+ cells which bound to YAC-1 cells, but failed to lyse them even after purification and subsequent exposure to interferon-alpha/beta in vitro. It appears, therefore, that in the absence of intact bone marrow, NK-1.1+ cells may be arrested in a nonlytic and interferon-unresponsive state. Spleens of neonatal mice which have low NK activity were analyzed to ascertain whether immature NK-1.1+ cells, similar to those found in estradiol-treated mice, could be demonstrated. Spleens of 8- to 9-day-old mice also contained NK-1.1+ cells which had very low NK activity even after purification. Sorted NK-1.1+ cells were examined for cytotoxicity in mice whose NK activity was suppressed by pretreatment with Corynebacterium parvum (-15 days). In contrast to cells from estradiol-treated and neonatal mice, NK-1.1+ from mice treated with C. parvum had normal functional activity. Similarly, although NK activity of unfractionated bone marrow cells is low, sorted NK-1.1+ cells were greatly enriched for lytic activity. Thus, we conclude that cell sorting with monoclonal anti-NK-1.1 antibody provides a powerful tool for examining the mechanisms underlying various states of low NK activity, and there exist NK-1.1+, nonlytic, interferon-unresponsive cells which apparently require an intact marrow microenvironment for differentiation into mature, lytic NK cells.
Early days of hospital dietetics.
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Immune recovery in children with malignancy after cessation of chemotherapy.
PURPOSE: To study longitudinally the extent and recovery of cellular and humoral immune alterations in children with cancer after completion of their therapy. PATIENTS AND METHODS: Using standard immune assays, cellular and humoral immunity was measured in 43 infants and children with cancer at completion of therapy and every 3 months thereafter for 1 year. There were 17 patients with acute lymphoblastic leukemia, 9 with Hodgkin disease, and 17 with solid nonhematopoietic tumors. All children had received standard childhood immunizations before diagnosis of cancer. Immune assays performed included circulating lymphocyte subpopulations, in vitro antigen-induced responses, and total concentrations of serum immunoglobulin G (IgG), IgM, IgA, and IgG subclasses, and specific antibodies against diphtheria, tetanus, pertussis, and poliovirus types I, II, and III. RESULTS: At completion of therapy, the majority of patients had low circulating lymphocyte subpopulations and antigen-induced responses. Serum antibody concentrations were low in up to 89% of patients regardless of the underlying malignancy. Although improvement occurred during the year of follow-up, 35 of 43 (81%) patients continued to exhibit one or more immune abnormalities 9 to 12 months after cessation of chemotherapy. Younger patients had more persistent alterations. Other risk factors studied (including gender, duration of therapy, and underlying malignancy) did not correlate with the severity of the immune defects. With the exception of poliovirus antibodies, specific antibody titers against common childhood vaccine antigens were deficient at completion of therapy and 9 to 12 months later in a substantial proportion of patients. CONCLUSION: Children with malignancy have persistent specific and nonspecific immune alterations 9 to 12 months after cessation of chemotherapy. The clinical implications of these in vitro observations are unclear and require further evaluation.
Has the RCN outlived its usefulness?
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