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Biomedical subjects

Mary Mitchell

Publications and source records attributed to Mary Mitchell.

8 recordsLinked to original sources
PubMed2004

Complex mechanisms for inhibition of immunoglobulin gene expression in a germinal center B cell line.

CD40 ligation and IL-4 stimulation are critical Th2 cell-derived signals that act on germinal center B cells to stimulate immunoglobulin isotype switching. In addition to this well-known effect, these same Th2 signals have also been reported to inhibit ongoing immunoglobulin synthesis in germinal center B cells. To study the mechanism of this inhibition, we have investigated which immunoglobulin gene regulatory regions might be affected by IL-4 and CD40 Ligand (CD40L). CL-01 cells, a human B cell line of germinal center phenotype, were transiently transfected with luciferase reporter constructs containing various light and heavy chain enhancers and promoters; the cells were then incubated with or without CD40L and IL-4 and then assayed for luciferase expression. We find that the intronic enhancer of the kappa light chain (but not the heavy chain) is upregulated by CD40 ligation, but that VH and Vkappa promoters and the 3' enhancers of both the kappa and heavy chain loci are inhibited by CD40 ligation and the Th2 cytokines IL-4 and IL-10. The inhibitory response of the 3'alpha enhancer can be observed with a 130 bp core fragment of the enhancer, and remains unaffected by mutations in several motifs known or suspected to contribute to enhancer function. The ultimate effects of cytokines and CD40 ligation on immunoglobulin gene transcription therefore represent a complex integration of positive and negative stimuli acting on enhancers and promoters.

Animals↗
PubMed2003

Using the cost distribution report in estimating private sector payments: what adjustments should researchers make?

OBJECTIVES: To reapportion Veterans Health Administration (VA) annual expenditures into benefit categories for comparison with estimated payments by private sector providers. METHODS: Total expenditures for six VA medical centers for federal fiscal year 1999 were reapportioned by benefit category using the cost distribution report (CDR). Health benefit categories were based on those of health care insurers. Cost reapportionment was based on CDR data and reviews of source accounting and payroll documents. RESULTS: Actual expenditures for many benefits can be accurately identified and reapportioned using CDR data, but other expenditures were not identifiable in the CDR and required inspection of source documents. Inpatient expenditures amounting to $75,110,094 US dollars and outpatient expenditures amounting to $73,594,284 US dollars were reapportioned into other benefit categories, primarily professional fees. Expenditures for some VA benefits could not be identified because of differences in accounting and clinical practice between the VA and the community. DISCUSSION: Revisions to bring the CDR more in line with private sector payment categories would improve effectiveness for internal VA analyses and external expenditure comparisons. CDR revisions would require changes in recording some clinical workload (eg, rehabilitation and extended care) and classifying residential and domiciliary programs separate from inpatient care. Benefits that were not assigned expenditures for comparison with payments represent a potential liability if the VA were to purchase health care services in the marketplace. Variation among hospitals on expenditures not clearly identified in the CDR was significant and raises questions about the effectiveness of capitated budget methodologies using either the CDR or the decision support system.

Cost-Benefit Analysis↗