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H R Macdonald

Publications and source records attributed to H R Macdonald.

14 recordsLinked to original sources

Political realities of statewide smoking legislation: the passage of California's Assembly Bill 13.

OBJECTIVE: To prepare a history of the enactment of California Assembly Bill 13 (AB 13), a state law prohibiting smoking in most workplaces passed in 1994, and to discuss its initial impacts. METHODS: Data were gathered from open ended interviews with representatives of voluntary health organisations, local government organisations, and principal legislators involved in the process, as well as observers around the state who could provide insight into the legislative process. Information was also obtained from legislative hearings and debates, public documents, letters and personal communications, internal memoranda, and news reports. RESULTS: The success of local tobacco control legislation in California led to a situation in which some health groups were willing to accept state preemption in order to attract the support of the state restaurant association for a bill. The decision to accept this preemption compromise was made by the state level offices of the voluntary health agencies without consulting the broader tobacco control community within California. In contrast, local tobacco control advocates did not accept this compromise, in part because of their belief that local legislation was a better device to educate the public, generate media coverage, and build community support for enforcement and implementation of clean indoor air and other tobacco control laws. Enactment of AB 13 was associated with a slowing of all local tobacco control legislation, including youth oriented laws. CONCLUSIONS: Because its supporters initially doubted that AB 13 would pass, there was never an effort to reconcile the policy differences between state oriented and locally oriented tobacco control policies. This lack of consensus, combined with the political realities inherent in passing any state legislation, led to a bill with ambiguous preemption language which replaced the "patchwork of local laws" with a "patchwork of local enforcement."

California↗

Precursor frequency analysis of lymphokine-secreting alloreactive T lymphocytes. Dissociation of subsets producing interleukin 2, macrophage-activating factor, and granulocyte-macrophage colony-stimulating factor on the basis of Lyt-2 phenotype.

The frequencies of precursors of C57BL/6 T lymphocytes that respond to DBA/2 alloantigens by secreting the lymphokines interleukin 2 (IL-2), macrophage-activating factor (MAF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been directly compared with cytolytic T lymphocyte precursor (CTL-P) frequencies in limiting dilution microcultures established from spleen cells positively or negatively selected on the basis of Lyt-2 phenotype. A clear dichotomy was observed between CTL-P, which were contained in the Lyt-2+ fraction, and precursors of IL-2-secreting cells, which were detected almost exclusively in the Lyt-2- population. In contrast, precursors of cells secreting MAF and GM-CSF were found in both populations: almost all responding cells from the Lyt-2- fraction produced both these factors, whereas the precursor frequency of MAF-secreting and GM-CSF-secreting cells was three- to fourfold lower in the Lyt-2+ population. These frequency data were consistent with quantitative differences observed in the average production of these lymphokines by Lyt-2+ and Lyt-2- populations.

Animals↗

Antibody-dependent cell-mediated destruction of human erythrocytes sensitized in ABO and rhesus fetal-maternal incompatibilities.

Antibody-dependent cell-mediated cytotoxicity (ADCMC) was measured in a 51Cr-release assay with antibody-sensitized human red blood cells (RBC) as target cells and nonimmune isologous or autologous mononuclear peripheral blood leukocytes (MPBL) as effector cells. ADCMC was readily demonstrable within 6 hr and was independent of exogenous complement (C'). The specificity of the ADCMC reaction was determined by the antiserum employed. Anti-A, anti-B, anti-D, and anti-c sera were all active in ADCMC; the specific lysis was between 35 and 50% with antiserum dilution of 1/1,000, using 10(5) target cells and 10(6) MPBL. Anti-C, anti-E, and anti-e sera had no detectable activity. Sephadex column separation suggested that this activity was by antibodies of the IgG class. Cord RBC from infants with RhD fetal-maternal incompatibility were lysed by autologous or isologous MPBL in the absence of exogenous antiserum. ADCMC was between 22% and42% in cases with high direct Coombs' test, but was negative with low direct Coombs' test as in five cases of ABO incompatibility.

ABO Blood-Group System↗

Generation of cytotoxic T lymphocytes in vitro. I. Response of normal and immune mouse spleen cells in mixed leukocyte cultures.

Mouse cytotoxic T lymphocytes (CTL) were generated in mixed leukocyte cultures (MLC) using spleen cells as responding cells and irradiated allogeneic spleen cells as stimulating cells. Cytotoxicity was assessed by a quantitative (51)Cr assay system and the relative frequency of CTL in individual cell populations was estimated from dose-response curves. Inclusion of 2-mercaptoethanol in the MLC medium resulted in a 20-40-fold increase in the relative number of CTL generated at the peak of the response. Under these culture conditions, cell-mediated cytotoxic activity was detectable in MLC populations as early as 48 h after the onset of the cultures. When spleen cells from mice immunized with allogeneic tumor cells 2-4 mo previously were cultured with irradiated spleen cells of the same alloantigenic specificity (MLC-Imm), it was found that the cell-mediated cytotoxic response was detectable earlier and reached higher levels than that observed in a primary MLC. At the peak of the response, MLC-Imm populations were observed to lyse up to 50% of the target cells within 3 h at a lymphocyte: target cell ratio of 0.3:1. Immunological and physical characterization of the effector cells generated in MLC-Imm indicated that they were medium to large-sized T lymphocytes. Altogether, these studies suggested the existence of an anamnestic cell-mediated cytotoxic response in MLC-Imm.

Animals↗

Generation of cytotoxic T lymphocytes in vitro. II. Effect of repeated exposure to alloantigens on the cytotoxic activity of long-term mixed leukocyte cultures.

Mouse cytotoxic T lymphocytes (CTL) were generated in unidirectional mixed leukocyte cultures (MLC) using normal C57BL/6 spleen cells as responding cells and irradiated DBA/2 spleen cells as stimulating cells. Cytotoxicity was assayed on (51)Cr-labeled P-815 (DBA/2) target cells, and the relative frequency of CTL in individual cell populations was estimated from dose-response curves. Upon inclusion of 2-mercaptoethanol in the culture medium, it was found that significant CTL activity could be detected for as long as 3 wk in primary MLC. Reexposure of MLC cells to the original stimulating alloantigens after 14-41 days in culture resulted in significant cell proliferation and rapid regeneration of high levels of immunologically specific cytotoxicity. CTL activity in these secondary cultures increased dramatically within the first 24 h and reached higher peak levels than those found at the peak of the primary response. Furthermore, proliferation and reappearance of CTL activity could be demonstrated following each of as many as four sequential alloantigenic stimulations of the same initial cell population at 20-day intervals. Interestingly, cells recovered from MLC at the peak of the primary response on day 4 were insensitive to further allogeneic stimulation. Taken together, these results are consistent with the hypothesis that CTL differentiate in MLC to become long-lived memory cells which gradually lose their cytotoxic activity. Upon reexposure to specific alloantigen, such memory CTL rapidly regain their functional activity and proliferate to generate an expanded CTL population.

Animals↗

Synchronization of mouse L-cells by a velocity sedimentation technique.

Differential velocity sedimentation at unit gravity has been used to separate an asynchronous population of mammalian cells into fractions synchronized in all phases of the cell cycle. Better enrichment was obtained for G(1) and S phases than for G(2)-M phase. Electronic cell volume measurements of the fractions indicated that the separation was primarily dependent on cell size, and an experimentally determined sedimentation coefficient agreed very well with its predicted value. Sources of dispersion in the separation (including the contribution of cell density heterogeneity) were quantitated and found to be insufficient to explain all of the observed dispersion. Both the limitations and the applications of the technique are discussed.

Animals↗