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Biomedical subjects

B B Lozzio

Publications and source records attributed to B B Lozzio.

At least 55 records · Page 3Linked to original sources

Hereditary asplenic-athymic mice: transplantation of human myelogenous leukemic cells.

A new animal model characterized by hereditary athymia and asplenia was used as a recipient of chronic myelogenous leukemic (CML) cells with the Philadelphia (Ph1+) chromosome. Transplanted CML cells form solid vascularized tumors containing cells similar to those seen in the patient in a long-term culture. Cells taken from the tumors were nearly triploid, retained all human chromosome markers, and had the same antigenic determinants(s) as cells in culture.

Abnormalities, Multiple↗

Human myelogenous (Ph+) leukemia cell line: transplantation into athymic mice.

Chronic myelogenous leukemia (CML) cells from line K-562, containing the Philadelphia (Ph1) chromosome, were transplanted into nude mice and grew as solid vascularized tumors containing cells like those seen in the patient and in the cultures. Cells taken from the tumors were near triphoid and retained all human chromosome markers in culture.

Animals↗

Cytotoxicity of antisera to a myelogenous leukemia cell line with the Philadelphia chromosome.

Rabbit antisera to myelogenous leukemia (ML) cells were raised; ML cells from line K-562 that has the Philadelphia (Ph) chromosome were used as antigen. Antibodydependent, complement-mediated cytotoxicity was demonstrated by the trypan blue test and Cr release assay for cultured ML cells, whereas no cytotoxicity was demonstrated for cells from B (SB) and T (MOLT 4) lymphoblastoid cell lines. The antisera showed no cross-reactivity for normal human peripheral leukocytes or purified granulocytes. A low level (less than 8%) of cytotoxicity was directed against cell membrane associated fetal bovine serum proteins. Absorption of the immune serum with normal human bone marrow cells of first trimester human whole embryo cells reduced the cytotoxic titer to a similar extent; this suggested the possibility of crossreactivity between ML cells and fetal antigen(s). However, the ML antigen(s) was unrelated to carcinoembryonic antigen (CEA), since absorption with CEA had no effect on the serum cytotoxic titer. The anti-ML sera were cytotoxic for cells taken from 10 patients with chronic myelogenous leukemia and from 3 with acute myelogenous leukemia. In contrast, the leukocytes of 1 of 4 patients with acute lymphocytic leukemia, and 3 of 7 with chronic lymphocytic leukemia shared similar antigenic determinants as demonstrated by cytotoxicity tests. The significance of the cross-reactivity of some lymphatic and ML cells may be the result of the use of rabbit sera that did not distinguish antigens common to both granulocytic and lymphocytic cells, or it may reflect an "immature" or "blastic" antigen present on many leukemia cells.

Adult↗

The lasat mouse: a new model for transplantation of human tissues.

A new animal model characterized by hereditary athymia and asplenia was developed by breeding congenitally athymic with hereditarily asplenic mice. The new hybrids have no cellular immunity and produce significantly less antibody than nude mice. The lasat mouse has been found useful for the transplantation of normal and malignant hemopoietic cells and other neoplastic tissues of human origin.

Animals↗

Absence of thymus-derived lymphocyte markers in myelogenous leukemia (Ph1+) cell line K-562.

The myelogenous leukemia cell line K-562 with a Ph1+chromosome, derived from a patient with chronic myelogenous leukemia in terminal blastic crisis, is not a bone marrow-derived lymphoblastic cell line, because the cells neither produce immunoglobulins nor possess complement receptors. Since it has been suspected that blasts found in some patients with chronic myelogenous leukemia in blastic crisis might be thymus-derived cells, we have studied several parameters to demonstrate that K-562 cells are not thymus-derived lymphoblasts. The results of this study show: (a) no cross-reactivity of antisera to K-562 cells with normal human thymocytes; (b) lack of cytotoxicity of a specific horse anti-human thymocyte globulin for K-562 cells; (c) failure of the treatment of K-562 cells with bovine thymosin to induce antigenic determinant and erythrocyte rosette receptors on K-562 cells; (d) presence of receptors for the Fc portion of immunoglobulin G; (e) absence of terminal deoxynucleotidyl transferase; and (f) cytotoxicity of monkey antiserum to K-562 cells for malignant thymus-derived cells (Molt-4). However, absorption with Molt-4 cells abolished the cross-reactivity with Molt-4 cells, whereas 60% of the antibody to K-562 cells remained in the immune serum. Studies of DNA polymerase activities revealed that K-562 cells have levels of polymerase alpha and beta, like other proliferating cells, and an RNA-dependent DNA polymerase activity, presumably representing polymerase gamma.

Antigens, Neoplasm↗

Infleuence of a neonatal spleen transplant on hematopoiesis of hereditarily asplenic mice.

Hereditarily asplenic mice and normal litternates were transplanted subcatneously with 20x10(6) congenic spleen cells at birth. Eighty per cent of the recipients developed subcutaneous nodules closely resembling the spleen structure seen ia a normal mouse. The growth of the graft was associated with hyperplasis of the majority of the bone marrow cellseries and an increased number of stem cells (CFU-spleen) and agar colony forming cells (CFC) per femoral shaft. Particularly noticeable was the hyperplasia of the granulocytic series which paralleled the increase of CFC number and of serum colony stimulating factor. The presence of the graft did not modify the erthrocytic seroes and the leukocytics of asplenic mice but reduced the average platelet count. It is xonxluded that the growth of the transplant was associated with the hematopoietic alteration described. These results would also indicate humoral or cellular influences of the spleen on the release of or production of marrow cells.

Animals↗

Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome.

A cell-line derived from a patient with chronic myelogenous leukemia (CML) is described. The new cell-line, which has over 175 serial passanges in a 3 1/2-yr period, has the following characteristics: (1) CML cells started to proliferate actively since they were first incubated in culture media. A threefold increase in the total number of cells was observed during the first seven passages; the cell population increased by a factor of 10 to 20 every 7 days from passage 8 through 85; from 20 to 40 times from passage 86 through 150, and more than 40 times after 150 passages. (2) The majority of the nononucleated cells are undifferentiated blasts. (3) The karyotype of all the cells examined show the Philadelphia (Ph1) chromosome and a long acrocentric marker plus aneuploidy. The Giemsa-banding studies identified the Ph1 chromosome as a terminal deletion of the long arm of chromosome 22:del(22)(q12) and the long acrocentric marker as an unbalanced reciprocal translocation of one chromosome 17 and the long arm of one chromosome 15. (4) The CML cells do not produce immunoglobulins, are free of mycoplasma, Epstein-Barr virus, and herpes-like virus particles. (5) CML cells have no alkaline phosphatase and myeloperoxidase activities and did not engulf inert particles. (6) Cultured CML cells provide a constant source of a specific antigen. This CML cell-line represents a unique source of CML cells with meaningful indicators of malignancy for clinical and experimental studies.

Alkaline Phosphatase↗