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ABSTRACT: Copy number variants are a recently discovered source of large-scale genomic diversity present in all individuals. We capitalize on these inherent genomic differences, focusing on deletion polymorphisms, to develop informative fluorescence in situ hybridization probes with the ability to unequivocally distinguish between donor and recipient cells in situ. These probes are accurate, specific, highly polymorphic and, notably, can be used to assign genetic identity in situ in a completely gender-independent fashion. We anticipate that these polymorphic deletion probes will be useful in further understanding the dynamics of cellular chimerism after transplantation, including the details of chronic organ rejection, post-transplant lymphoproliferative disorder and graft-versus-host disease, and in optimizing future tissue engineering and pluripotent stem cell therapies.
Nature medicine 02/2009; 15(2):215-9. · 27.14 Impact Factor
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ABSTRACT: CD10 has been recently advocated as a good immunohistochemical marker for endometrial stromal tumors. Metastatic endometrial stromal tumors to the ovary and primary endometrioid stromal sarcomas may show overlapping histological features with pure stromal and sex cord-stromal tumors (SCSTs). We investigated CD10 expression in a large series of pure stromal and SCSTs of the ovary to ascertain whether CD10 may aid in this differential diagnosis. Archival material from 11 fibromas, 10 thecomas, 10 sclerosing stromal tumors (SSTs), 10 adult granulosa cell tumors (AGCTs), 4 luteinized AGCTs, 9 juvenile granulosa cell tumors (JGCTs), 9 Sertoli cell tumors, 9 Sertoli-Leydig cell tumors, 11 sex cord tumors with annular tubules, 10 steroid cell tumors (StCTs), and 8 fibrosarcomas of the ovary were immunostained for CD10. The percentage of cells stained (<5%, 5%-39%, 40%-75%, and >75%) and intensity of staining (1+, 2+, 3+) were evaluated. CD10 was expressed in 7 of 10 thecomas (4 with 5%-75% and mostly 1+), 9 of 10 SSTs (7 with 5%-39% + cells, mostly 1+), 9 of 10 AGCTs (<5%-39%, four 1+, five 2+), 1 of 4 luteinized AGCTs (<5% and 1+), 8 of 9 JGCTs (mostly <5% to 39% and +1), 4 of 9 Sertoli cell tumors (either focal or >75% with variable intensity), 4 of 9 Sertoli-Leydig cell tumors (mostly <10% with variable staining), with the Leydig cells being positive in only 1 tumor (1+ and <5%), and 7 of 10 StCTs (4 tumors with more than 75% + cells, from 1+ to 3+). All fibromas, all but 1 fibrosarcoma (<5% and 1+), and all sex cord tumors with annular tubules were CD10 negative. CD10 expression was frequently seen in StCTs, SSTs, and thecomas of the ovary, although the latter 2 categories usually showed only faint immunoreactivity. In conclusion the frequency and intensity of CD10 immunoreactivity in pure stromal and sex cord-stromal ovarian tumors are low and contrast with the typical strong and diffuse immunostaining seen in endometrial stromal tumors; however, faint CD10 positivity is consistent with the diagnosis of ovarian SCST. Steroid cell tumors are often positive for CD10, but these tumors do not pose problems in differential diagnosis with endometrial stromal tumors. CD10 may play a useful role in aiding the differential between endometrial stromal tumors in the ovary and SCST and stromal tumors.
International Journal of Gynecological Pathology 11/2007; 26(4):359-67. · 1.45 Impact Factor
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ABSTRACT: Intratracheal (IT) administration of heat-killed Listeria monocytogenes (HKL) results in an influx of macrophage and dendritic cell (DC) precursors into the lung interstitium. Low-density, FcR+, interstitial lung cells isolated from rats instilled 24 hr before with HKL or vehicle alone, were > 90% Mar1+. After culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) for 3 days, up to 24% of the loosely adherent cells were DC that stimulated allogeneic T-cell proliferation in an mixed lymphocyte reaction (MLR) assay. After only an overnight incubation with GM-CSF, however, the capacity of interstitial Mar1+ cells to stimulate HKL immune T-cell proliferation without exogenous antigen was low. By contrast, when DC were isolated as major histocompatibility complex (MHC) class II+ cells from rat lungs at 1, 3, 7 and 14 days after HKL instillation and cultured overnight with GM-CSF, their antigen presentation capacity without added exogenous antigen was robust, but declined over the 2-week period. Interestingly, hilar lymph node DC maintained their HKL antigen-presenting capacity for up to 2 weeks after instillation of HKL. Following IT administration of PKH-26 labelled HKL, fluorescent or immunolabelled organisms were detected in OX62+ DC in airway epithelium, lung interstitium and hilar lymph nodes in situ and in MHC class II+ DC isolated from these sites. We conclude that newly immigrated Mar1+ lung DC precursors, while efficient in endocytosing particulate antigens, are incapable of eliciting a significant proliferative response from HKL-sensitized T cells. By contrast, MHC class II+ DC isolated from lungs and incubated overnight with GM-CSF induce vigorous antigen-specific T-cell proliferation. Antigen-loaded lung DC in hilar lymph nodes maintain their antigen presentation capacity for up to 2 weeks.
Immunology 04/2002; 105(4):488-98. · 3.32 Impact Factor
