Suppressed Cell-Mediated Immunity and Monocyte and Natural Killer Cell Activity Following Allogeneic Immunization of Women with Spontaneous Recurrent Abortion

Spontaneous recurrent abortion (SRA) has been treated by means of immunization with paternal or third-party white blood cells, yet the immunological basis for SRA and for the role of immunization protocols in pregnancy outcome remains controversial. To elucidate this question, nine women with SRA were immunized with paternal mononuclear cells and studied before and 2 weeks after immunization. Seven women who became pregnant gave birth to live newborns. Secretion of the T helper 1 cytokines IL-2 and interferon- by patients' mononuclear cells decreased, while production of IL-10 increased. The levels of natural killer and lymphokine-activated killer cell-mediated cytotoxicity were markedly decreased. Monocyte functions such as secretion of IL-l, tumor necrosis factor a, IL-6, and cytotoxic activity decreased concurrently with elevations in IL-10 and transforming growth factor secretion. Production of IL-12, a pivotal regulatory cytokine, decreased. Furthermore, B7/1 expression on patients' mononuclear cells was downregulated. This resulted in a decrease in monocyte costimulatory activity of purified T cells with soluble anti-CD3, paralleled by a decline in allogeneic proliferative responses. These results suggest that the improved pregnancy success rate in women with SRA following immunization may be partly related to suppression of cell-mediated immunity and monocyte and natural killer cell activity.     

Influence of the time of day on physical performance in patients with coronary artery disease

The exercise training workload for cardiac patients is determined from the peak heart rate achieved safely during a stress test. Circadian rhythms may play a key role in changing physiological responses to the stress test. Therefore, the purpose of this study was to evaluate the influence of the time of day on cardiopulmonary and metabolic responses in highly trained men with coronary artery disease. A group of 15 patients with coronary artery disease [53.5 (SD 6) years] performed two sessions of graded tests to exhaustion: one session was performed at 10 a.m. and the second at 5 p.m. in randomized order. Treadmill velocity was kept constant at a speed of 4.8 km · h^–1 starting with an elevation of 0% which was increased thereafter by 2.5% every 3 min. At rest the results revealed that only oxygen uptake was significantly lower (P < 0.05) in the morning compared to that observed in the evening [2.9 (SD 0.4) compared to 3.5 (SD 0.5) ml O₂ · kg^–1 · min^–1, respectively]. During exercise, differences due to time of day were found in the variables of maximal oxygen uptake which were significantly higher (P < 0.05) in the evening than in the morning [34.2 (SD 2.6) and 40.8 (SD 2.5) ml O₂ · kg^–1 · min^–1, respectively]. These data indicated that in these well-trained coronary artery disease patients there was a significant time of day effect associated with metabolic responses following stress-testing.     

Mathematical modelling of objectives in radiation therapy treatment planning.

We view radiation therapy treatment planning (RTTP) as a problem of constrained optimization. In this context, the 'optimal' treatment is one that maximizes some objective function subject to the inherent constraints of the problem. We discuss two objective functions which are motivated by biological considerations rather than mathematical expedience. One of these measures the 'goodness' of a treatment in terms of its probability of success. The other measures the degree to which a treatment succeeds in satisfying a system of constraints that are mutually contradictory. We describe how to actually perform the optimization of these objective functions in practice and show some numerical results which demonstrate advantages of these objective functions over their more conventional counterparts.     

Trimellitic anhydride-induced airway syndromes: Clinical and immunologic studies

This report describes a spectrum of respiratory symptoms in workers exposed to trimellitic anhydride (TMA), a biologically reactive chemical used in the plastics industry. Fourteen workers who had worked on a unit which synthesized TMA were evaluated by clinical and immunologic methods. Respiratory syndromes induced by TMA inhalation included asthma and rhinitis of the immediate type, late onset asthma with systemic symptoms, and airway irritation. TMA was shown to couple rapidly to human serum albumin, forming an immunoreactive hapten-protein complex. The workers' immunologic reactivity to this complex could be quantitated and correlated with the three respiratory syndromes. The asthma-rhinitis syndrome was mediated by IgE antibody specific for the TMA hapten. The syndrome of late onset asthma with systemic symptoms was accompanied by elevated levels of TMA-specific IgG antibody. Rheumatoid factor in high titer was found in one worker with IgE-mediated asthma and in two workers with asthma of late onset. Lymphocyte reactivity of TMA-HSA was demonstrated in three workers representative of the three clinical syndromes. Leukocyte histamine release was demonstrated to TMA-HSA in one worker with high levels of IgE antibody specific for TMA-HSA who had severe symptoms of acute rhinitis and asthma.