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F D Wilson

Publications and source records attributed to F D Wilson.

At least 55 records · Page 3Linked to original sources

Production of mesenchymal tumors in nude mice by Ph1 negative fibroblasts obtained from a Ph 1 positive CML patient: a preliminary report.

An experimental model system is presented for the investigation in humans of the role of hematopoietic stromal elements in the regulation of hematopoiesis as well as in the pathogenesis of myelofibrosis in myeloproliferative disorders. The model is based on the simultaneous application of three experimental techniques: (1) growth of bone-marrow derived fibroblastic colonies in vitro, (2) cytogenetic demonstration of marker chromosomes associated with hematopoietic malignancies, and (3) the transplantation of isolated stromal elements into athymic (nude) mice. Using this model, we describe the induction of mesenchymal tumors in nude mice by Ph1 negative fibroblasts obtained from the bone marrow of a patient with a Ph1 positive chronic myelogenous leukemia. Mesenchymal tumors also were induced in nude mice with bone marrow-derived fibroblasts from a patient with aplastic anemia, who was successfully treated with bone marrow transplantation, and from a normal human volunteer. Morphologic, cytogenetic and electron microscopic studies of bone marrow mesenchymal elements in culture and of tumors induced in nude mice from the CML patient indicate the cells composing the tumor are of human origin and are negative for the Ph1 chromosome. The results provide the first in vivo morphological and cytogenetic support using human materials, of the hypothesized relationship of progenitors of in vitro fibroblastic colonies to marrow stromal elements.

Animals↗

Growth of canine T-lymphocyte colonies in vitro.

Canine lymphocytes from peripheral blood, lymph nodes, thymus and bone marrow were stimulated with phytohemagglutinin-P (PHA) or concanavalin-A (CON-A) to form colonies in methylcellulose. Lymphocytes exposed to mitogens in liquid phase formed clumps the size of colonies. Lymphocyte clumping was eliminated by plating cells directly into methylcellulose, but high concentrations of mitogens (CON-A or PHA is greater than 10 mg/10(6) lymphocytes) were required in order to get subsequent colony formation. Thus, in contrast to published reports, exposure of lymphocytes to mitogen prior to plating was not required for cloning of canine peripheral blood lymphocytes. Colonies from thymus, lymph node, or peripheral blood consisted predominantly of T lymphocytes, whereas cultures from bone marrow also produced colonies with macrophage morphology and surface-adherent colonies with mesenchymal morphology.

Animals↗

Comparison of whole blood and purified canine lymphocytes in a lymphocyte-stimulation microassay.

The optimum mitogen concentration and time required for using whole blood from dogs in a microassay were determined, and this test then was compared with a standard lymphocyte-stimulation microtest, using gradient-isolated lymphocytes, 2 different mitogens (phytohemagglutinin and concanavalin A), and 2 different culture media. Statistical analysis of the data from 10 dogs showed that whole blood was significantly more reactive than were gradient-isolated lymphocytes (P less than 0.05). Waymouth's medium was significantly better than RPMI 1640 (P less than 0.001), and concanavalin A was significantly more mitogenic than phytohemagglutinin (P less than 0.001). The interaction between lymphocyte source and mitogens was the only one of the various interactions that was significant at P less than 0.05.

Animals↗

Increased clonogenic (CFU-C, PFU-C) populations from bone marrow and spleen of nude mice.

Clonogenic populations from bone marrow and spleen of nude mice and their normal littermates were enumerated in vitro using a methylcellulose supported culture system. This technique allows for the simultaneous quantitation of progenitors of granulocyte-monocyte pathways (colony forming units in culture, CFU-C) and for progenitors of "mesenchymal" elements (plaque-forming units in culture or PFU-C). These populations were distinguished in culture by their growth, characteristics and morphology. CFU-C gave rise to suspended colonies of granulocyte-monocyte composition while PFU-C formed surface-adherent colonies of mesenchymal morphological features (fibroblastic and reticuloendothelial morphology). Significant elevations in the relative and absolute numbers of CFU-C and PFU-C were observed in the bone marrow and spleen of 6 wk old nu/nu mice relative to heterozygous littermates. The results are discussed in terms of non-T cells components involved in cell-medited immunity against neoplastic development.

Age Factors↗

Some observations of the hematopoietic status in vivo and in vitro on mice of genotype S1/S1d.

Studies on the mechanism of anemia in mice of genotype S1/S1d have implicated the hematopoietic stroma (the hematopoietic inductive microenvironment, HIM) rather than hematopoietic stem cells as the site of the defect. Using methylcellulose-supported bone marrow culture systems, we have observed, in addition to classical hematopoietic colonies, the formation of surface associated fibroblastic plaques that could stimulate hematopoietic colony growth. These plaques were hypothesized to be derived from bone marrow stroma precursors. In view of the reported stromal-based defect in S1/S1d mice, studies were initiated, using our culture system, to determine if abnormalities exist in the plaque-forming potentials of these mice. Relative to controls, bone marrow derived from S1/S1d mice exhibited a significant decrease in hematopoietic colonly-forming units in culture, but no differences were apparent in the absolute numbers of fibroblastic plaque-forming units or in the ability of such plaques once derived to stimulate hematopoietic colony growth when overlain with fresh normal bone marrow preparations. Quantitative studies on the bone marrow of the S1/S1d mice revealed a marked reduction in total nucleated cells per femur. The importance of evaluating the results of bone marrow cultures in an absolute (i.e., number of units per femur) rather than a relative (i.e., number of units forming in a constant cell inoculum) term was underlined by these studies.

Anemia↗