Biomedical subjects

D Izon

Publications and source records attributed to D Izon.

5 recordsLinked to original sources

PubMed2001

A common pathway for dendritic cell and early B cell development.

B cells and dendritic cells (DCs) each develop from poorly described progenitor cells in the bone marrow (BM). Although a subset of DCs has been proposed to arise from lymphoid progenitors, a common developmental pathway for B cells and BM-derived DCs has not been clearly identified. To address this possibility, we performed a comprehensive analysis of DC differentiative potential among lymphoid and B lymphoid progenitor populations in adult mouse BM. We found that both the common lymphoid progenitors (CLPs), shown here and elsewhere to give rise exclusively to lymphocytes, and a down-stream early B-lineage precursor population devoid of T and NK cell precursor potential each give rise to DCs when exposed to the appropriate cytokines. This result contrasts with more mature B-lineage precursors, all of which failed to give rise to detectable numbers of DCs. Significantly, both CLP and early B-lineage-derived DCs acquired several surface markers associated with functional DCs, and CLP-derived DCs readily induced proliferation of allogeneic CD4(+) T cells. Surprisingly, however, DC differentiation from both lymphoid-restricted progenitors was accompanied by up-regulation of CD11b expression, a cell surface molecule normally restricted to myeloid lineage cells including putative myeloid DCs. Together, these data demonstrate that loss of DC developmental potential is the final step in B-lineage commitment and thus reveals a previously unrecognized link between early B cell and DC ontogeny.

Aging↗

PubMed1996

Development and characterization of v-myc/v-raf-transformed murine fetal thymocyte cell lines.

Transformed murine fetal thymocyte cell lines were derived by incubating fetal thymic organ cultures with a v-myc/v-raf-containing retroviral construct in order to model developmental stages within the early triple negative (CD3-CD4-CD8-) thymocyte population. The resulting 10 cell lines had a lymphoid morphology, were all CD44+, CD90+, and were triple negative by surface antigen analysis. The cell lines, however, were distinguishable by differences in the expression of T cell-associated and T cell-specific genes. The CD3 genes were observed to be discoordinately expressed, in that CD3 gamma chain gene expression was detected in 2 cell lines in the absence of CD3 delta and epsilon expression. Expression of the CD3 gamma chain gene was observed in cell lines without the expression of other T cell-specific genes or T cell receptor rearrangement and may be one of the earliest T cell-specific genes to be expressed. The transcription factor Ikaros was expressed in all 10 cell lines, whereas the transcription factor TCF1 alpha was expressed only in the 2 most differentiated lines. In 8 cell lines, expression of partial TCR beta and/or TCR alpha transcripts was observed by Northern blot. In several lines, expression of rearranged TCR alpha transcripts in the absence of TCR beta transcripts was demonstrated; however, TCR beta DJ rearrangements were observed by Southern blot in all but 1 of these cell lines. Thus, these cell lines, ordered based on the general pattern of additive gene expression observed, may reflect various stages of triple-negative thymocyte differentiation and provide an in vitro mechanism to elucidate some of the molecular events involved in early thymocyte development.

Animals↗

PubMed1995

An HMG-box-containing T-cell factor required for thymocyte differentiation.

Two candidate genes for controlling thymocyte differentiation, T-cell factor-1 (Tcf-1) and lymphoid enhancer-binding factor (Lef-1), encode closely related DNA-binding HMG-box proteins. Their expression pattern is complex and largely overlapping during embryogenesis, yet restricted to lymphocytes postnatally. Here we generate two independent germline mutations in Tcf-1 and find that thymocyte development in (otherwise normal) mutant mice is blocked at the transition from the CD8+, immature single-positive to the CD4+/CD8+ double-positive stage. In contrast to wild-type mice, most of the immature single-positive cells in the mutants are not in the cell cycle and the number of immunocompetent T cells in peripheral lymphoid organs is reduced. We conclude that Tcf-1 controls an essential step in thymocyte differentiation.

Animals↗

PubMed1994

Phase I clinical evaluation of a new murine monoclonal antibody (Mu-9) against colon-specific antigen-p for targeting gastrointestinal carcinomas.

BACKGROUND: Colon-specific antigen-p is a tumor-associated antigen present in approximately 60% of colorectal cancers. Preclinical studies have shown that the murine monoclonal antibody Mu-9 has excellent tumor-targeting abilities; therefore, clinical studies were initiated. METHODS: The immunoglobulin G and F(ab')2 were radiolabeled with 131I and administered to 13 and 12 patients, respectively, with advanced gastrointestinal cancer (colon, rectal, and pancreatic) for radioimmunodetection or radioimmunotherapy. RESULTS: Even in patients with highly elevated carcinoembryonic antigen levels, only one patient showed appreciable complexation of the labeled antibody, suggesting the epitope may not be highly expressed in the blood. Fifty percent of 131I-Mu-9 immunoglobulin G was cleared from the blood within 41 +/- 13 hours, while it took only 19 +/- 8 hours for the same amount of 131I-F(ab')2 to be cleared from the blood. Lesion detection in the abdomen, liver, and pelvis was greater than 90% for either the immunoglobulin G or F(ab')2. The dose absorbed by the normal organs, except the kidneys, was two- to threefold less for the F(ab')2 than for the whole immunoglobulin G. The dose to the kidneys was similar for both forms of immunoglobulin. The average tumor dose for 131I-Mu-9 immunoglobulin G was 13.9 +/- 11.0 cGy/mCi, and for 131I-F(ab')2 was 4.9 +/- 2.9. Tumor/red marrow dose ratios for the whole immunoglobulin G were 4.3 +/- 3.0, compared to 3.3 +/- 1.9 for the F(ab')2, suggesting the therapeutic window for the two forms of immunoglobulin may be similar. Eight of nine patients given the whole immunoglobulin G developed highly elevated levels of human anti-mouse antibody, whereas lower values were observed in five of seven patients given the F(ab')2. CONCLUSIONS: These initial results support the need for further evaluation of Mu-9 immunoglobulin G and F(ab')2 for targeting gastrointestinal cancer for radioimmunotherapy.

Adult↗

PubMed1993

Postsurgical radiation therapy for prophylaxis of heterotopic ossification.

Radiation therapy has been shown to be the most effective prophylactic measure against heterotopic ossification (HO) in surgically repaired hip fractures. Current research is seeking the minimum effective dose of radiation. The authors present four case reports and a review of the literature on HO.

Adult↗