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Effect of interferon on dimethyl sulfoxide-stimulated Friend erythroleukemic cells: ultrastructural and biochemical study.

Treatment of dimethyl sulfoxide-stimulated Friend erythroleukemic cells (clone 745) with mouse interferon (50 U/ml) led to the following changes: (i) a net decrease (40 to 60%) in both the total number of apparently newly synthesized virion particles per cell section and in the average number of cell sections containing one or more virion particles; (ii) a large decrease (80 to 90%) in the number of particles released into the supernatant fluid, as assayed by reverse transcriptase activity; (iii) an initial increase in the number of "immature" or "enveloped A-type" virions followed by an increase in the accumulation of empty, core shell-like particles; and (iv) a decrease in the number of cytoplasmic vacuolar structures, which have been implicated as a major site of virus production and which we show here by serial sectioning to be, in several instances, invaginations of the plasma membrane. The effects on virus production were noticeable 2 h after interferon addition and reached their full extent by 13 h. We conclude from these observations that interferon acts upon the late stage(s) of virion maturation, leading both to a decrease in virion production as well as to the formation of defective particles. In contrast, a small but significant increase in the rate at which globin mRNA and hemoglobin accumulate is observed after interferon treatment.

Animals↗

A v-H-ras-dependent hemopoietic tumor model involving progression from a clonal stage of transformation competence to autocrine interleukin 3 production.

Autocrine interleukin 3 (IL-3)-secreting tumors were generated from an IL-3-dependent mouse mast cell line (PB-3c) after introduction of the v-H-ras oncogene. Tumor progression was characterized by four distinct phenotypes. The first corresponded to immortalized mast cells unresponsive to the oncogenic effect of v-H-ras. The second was expressed in a clonable subpopulation of PB-3c cells and was marked by the competence to form v-H-ras-dependent tumors (immortalized transformation competence). The third was a direct effect of v-H-ras expression on all PB-3c cells and was characterized in vitro by a reduced IL-3 requirement. Upon injection of v-H-ras-expressing, transformation-competent cells into mice, the final, fully malignant phenotype developed with a long latency period and was marked in vitro by independence of exogenous IL-3 and by autocrine IL-3 stimulation. Northern (RNA) blot analysis and an RNase A-T1 protection assay showed that IL-3 production was strictly associated with the tumor phenotype. Two of six tumors showed an alteration at the 5' region of the IL-3 gene. We conclude that v-H-ras required complementation by IL-3 gene rearrangement or an alternate event to generate autocrine mastocytomas.

Animals↗

Subtracting insult from injury: addressing cultural expectations in the disclosure of medical error.

This article proposes that knowledge of cultural expectations concerning ethical responses to unintentional harm can help students and physicians better to understand patients' distress when physicians fail to disclose, apologize for, and make amends for harmful medical errors. While not universal, the Judeo-Christian traditions of confession, repentance, and forgiveness inform the cultural expectations of many individuals within secular western societies. Physicians' professional obligations concerning truth telling reflect these expectations and are inclusive of the disclosure of medical error, while physicians may express a need for self-forgiveness after making errors and should be aware that patients may also rely upon forgiveness as a means of dealing with harm. The article recommends that learning how to disclose errors, apologize to injured patients, ensure that these patients' needs are met, and confront the emotional dimensions of one's own mistakes should be part of medical education and reinforced by the conduct of senior physicians.

Attitude of Health Personnel↗