Recent reports of “lineage switching” from a lymphoid to macrophage phenotype have
left unresolved the question of whether such cells are functional macrophages or
nonfunctional products of differentiation gone awry. This study demonstrates that
several “macrophage-like” cell lines derived from v-Ha-ras-transformed pre-B cells have
gained the capacity to effectively present antigen in MHC-restricted fashion. Using an
assay involving the cocultivation of putative antigen-presenting cells with chicken
ovalbumin (cOVA) and a cOVA-specific T-cell hybridoma, “lineage switch” cell lines
were found to present antigen as effectively as macrophage-containing peritoneal
exudates. Neither the original pre-B-cell precursors nor B-cell lymphomas derived from
them present antigen. Thus, we have demonstrated that these “lineage switch”
macrophages are capable of antigen presentation, a mature differentiated function.
While gaining macrophage characteristics, these cells have also rearranged their
kappa light-chain immunoglobulin locus, suggesting that macrophage differentiation
and immunoglobulin rearrangement are not mutually exclusive processes. The existence
of both lymphoid and myeloid characteristics in a cell fully capable of antigen
presentation suggests greater plasticity in hematopoietic lineage commitment than
conventionally thought to be the case.
Background: The ability to identify asymptomatic women at high risk for breast cancer using known pre-malignant changes in exfoliative cytopathology of nipple aspirate fluid is of clinical importance. Exfoliative cytopathology of Nipple Aspirate Fluid (NAF) has been shown to be an important adjunct to the currently accepted standard of medical care, i.e. mammography, coupled with physical examination, for the diagnosis of breast cancer. This is especially important for the subset of women aged 18-50 who are not identified as "high risk", and therefore, for whom mammography is not routinely recommended. The objective of this study was to determine if a new, patented Class II medical device, the Mammary Aspirate Specimen Cytology Test (MASCT) System, designed to collect NAF for subsequent cytological examination is safe and effective. Methods: The MASCT medical device is a modified breast pump and was used to obtain bilateral specimens from 34 healthy, non-pregnant, female subjects for cytopathological examination. A conventional breast disease work-up was performed (medical history/risk factor collection, clinical breast examination and mammogram) and NAF specimens were collected. Specimen weight was measured and a cytopathological examination was performed. Vital signs measurements, clinical laboratory analysis, and adverse event reporting were performed. Results: Based on cytopathological evaluation and/or measurable weight changes on the specimen collection membrane filter, all breasts evaluated (100%) yielded nipple aspirate fluid. Specimen weights ranged from <1 to 37 mg and all specimens evaluated cytopathologically were deemed to be clinically useful. One patient's specimen was not available for cytopathological examination due to specimen mishandling, resulting in 60 breasts (representing 30 subjects) being evaluated cytologically. Fifty-eight of sixty breasts evaluated cytopathologically (97%) were reported as cytology Class I, and 2 of 60 (3%) were reported as cytology Class IIa. Cytopathological findings correlated well with mammogram and clinical breast exam results. No adverse events, including pain from the collection procedure, were reported. Conclusion: Based on this clinical study, we conclude that the Mammary Aspiration Specimen Cytology Test device is safe and effective for the collection of mammary aspirate specimens for laboratory cytopathological testing.
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