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Articles by Richard J. Weber
Total Records ( 3 ) for Richard J. Weber
  Ricardo Gomez-Flores , Diana Caballero-Hernandez , Richard J. Weber , Reyes Tamez-Guerra , Patricia Tamez-Guerra and Cristina Rodriguez-Padilla
  Norepinephrine (NE) has been associated not only with increasing blood pressure, atherosclerosis, heart disease, and other life threatening conditions, but also with altering immune responses by influencing leukocyte functions. In the present study, we evaluated the in vitro effects of NE on rat thymic lymphocyte and human peripheral blood mononuclear cells (HPBMC) functions. We observed that NE marginally, but significantly (P < 0.01) enhanced (1.3-fold increase) proliferation of rat thymic lymphocytes at 10-5 M, without altering HPBMC proliferation, as compared with untreated control. In addition, NE (10-5 M) significantly (P < 0.01) enhanced nitric oxide production (2.9 + 0.095 nmol/well) (which reduced 20% cell viability), and stimulated (P < 0.01) TNF-α production (4 + 0.16 pg/ml) by rat macrophages. NE (10-5 M) was also observed to induce 2-fold increase in mRNA signal of TNF-α, and stimulated that of IL-1 and IL-6 by HPBMC, as compared with untreated control. Taken together, these results indicated that NE was capable to activate in vitro rat and human lymphocyte and macrophage pro-inflammatory response.
  Ricardo Gomez-Flores , Kimberly R. Vietti , William J. Dunn III , Reyes Tamez-Guerra and Richard J. Weber
  Opioids can suppress immune functions and increase susceptibility to developing cancer and infectious diseases. Recently, novel opioid compounds have been synthesized that lack immunosuppressive effects. We evaluated the effects of morphinans with substituted pyrimidine (methyl, phenyl, hydroxy, and amino groups) and pyrazole groups on in vitro rat thymic lymphocyte and splenic macrophage functions, and tumor cell growth. We observed that morphinans with methyl, phenyl, hydroxy, amino, and pyrazole groups at concentrations from 10-10M to 10-5M plus Con A (2.5 μg/ml) significantly (P < 0.01) induced 2- to 2.9-, 2.3- to 6.4-, 2.4- to 3.4-, 2.6- to 3.4-, and 2.6- to 3.2-fold increases respectively in thymic lymphoproliferation compared with Con A alone; this effect was reversed by naloxone. Macrophage nitric oxide production was not altered by morphinans. In addition, we observed that all tested morphinans were associated with significant (P < 0.01) in vitro tumor cell growth inhibition of J774A (18-41%), L929 (12-36%), L5178 (9-15%) cell lines in a dose-dependent manner, at doses ranging from 10-11M to 10-5M. Morphinans may be applied in clinical situations where immunosuppression is undesirable.
  Richard J. Weber , Ricardo Gomez-Flores , Ichiro Sora and George R. Uhl
  In vivo administration of μ-opioid receptor selective agonists to various species is known to suppress lymphocyte, NK cell, and macrophage functions, in addition to mediate pain relief and euphoria. Using a mouse model in which the μ-opioid receptor gene was disrupted by targeted homologous recombination, we explored the involvement of this receptor in natural killer (NK) cell activity and T lymphocyte function. Following peripheral morphine administration, NK cell activity was not affected in homozygous μ-opioid receptor knockout mice, heterozygous animals marginaly responded to the immunosuppressive effects of the drug, while wild-type animals were significantly suppressed. In addition, splenic T-cell proliferative responses to concanavalin A, phytohemaglutinin and an antibody to T-cell receptor (TCR) plus interleukin-2 were not affected by morphine treatment in μ-opioid receptor knockout homozygous and heterozygous mice, whereas morphine significantly suppressed T-cell proliferation in wild-type mice. Taken together, these results suggest a role of the µ-opioid receptor in immunoregulation.
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