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Biomedical subjects

B B Lozzio

Publications and source records attributed to B B Lozzio.

At least 19 recordsLinked to original sources
PubMed1979

High incidence of mammary tumors in mice with inherited asplenia carriers for the nude gene.

A colony of mice suffering from dominant hemimelia associated with agenesis of the spleen has been developed and characterized during the past 7 years. The hereditarily asplenic (Dh/+) mice have a very low incidence (9%) of spontaneous mammary tumors (SMT). Asplenic (Dh/+) females were mated with mice homozygous (nu/nu) for hereditary athymia (nude) having a BALB/c background. BALB/c females heterozygous for the nu gene and with spleen (nu/+,+/+) have a moderate incidence (12%) of SMT, whereas nu/+,Dh/+ breeders have a drastic increase in the incidence of SMT to 46% when bred under identical conditions. Since all parent strains have a very low incidence of SMT, it appears that the spleen agenesis is a major factor accounting for an earlier and higher incidence of SMT in hereditarily asplenic (nu/+,Dh/+) mice than in normal (nu/+,+/+) siblings. The SMT express mammary tumor virus antigen(s) and possess estrogen, progesterone, and glucocorticoid receptors. The SMT rapidly metastasize and kill the host within 30 to 45 days. The BALB/c asplenic mice with SMT represent a unique model relevant to human breast cancer and for study of the function of the spleen in the development of solid tumors in general and of SMT in particular.

Animals↗
PubMed1979

Reproducible metastatic growth of K-562 human myelogenous leukemia cells in nude mice.

A reproducible metastatic growth of K-562 human myelogenous leukemia cells occurred in immunodeficient athymic (nude) mice. Although previous studies have shown that K-562 cells grow as local subcutaneous myelosarcomas which continuously release leukemia cells into the systemic circulation in adult mice, metastases were not observed. However, the subcutaneous "priming" of newborn nude mice resulted in the metastatic proliferation of leukemia cells in the lungs, kidneys, brain, and lymph nodes. Three sc injections of 5 X 10(6) K-562 cells on days 1, 7, and 14 of life produced metastases in 51% of the mice. When the initial series of injections was followed by iv injections on days 35 and 42, the incidence of metastases increased to 67%. Karyotypes demonstrated that the tumor cells retained the same human chromosome markers as those in the human patient and tissue culture. These procedures may provide a model for study of the mechanisms of metastases and for chemotherapeutic and immunotherapeutic trials against metastases of neoplasms of human origin.

Animals↗
PubMed1979

Heterotransplantation of human neoplasms.

The heterotransplantation of 39 solid human neoplasms into athymic and asplenic-athymic mice resulted in the successful growth of 28 of the transplants. However, only 17 of the tumors could be maintained in serial passage. Metastasis or local infiltration by the transplanted tumors was not observed. Melanomas and colorectal carcinomas grew well whereas other types grew poorly or not at all. Possible factors responsible for the poor growth or lack of growth are discussed. The rapid growth of a melanoma in newborn mice in contrast with the slow growth of the same tumor in adult mice suggests a new experimental approach for transplantation of malignancies which previously have been difficult to establish.

Animals↗
PubMed1979

Hematopoiesis of hereditarily asplenic-athymic (lasat) mice.

The hematopoiesis of athymic-asplenic (lasat) mice was compared with that of normal, asplenic, and athymic littermates with the same strain background. Erythrocyte blood volume, number and survival time were normal when related to the body weight of the animals. Peripheral blood showed leukopenia with absolute and relative lymphopenia, resembling the athymic rather than the asplenic pattern. The bone marrow was hypocellular as a consequence of a decrease in both lymphocytes and erythroid precursors, while thrombocytopoiesis and granulcytopoiesis-monocytopoiesis were essentially normal. Although the percentile value of femoral stem cells was high, their absolute number was, in fact, reduced by 35% as a result of the bone marrow hypocellularity. When lasat bone marrow cells were injected into normal, lethally irradiated mice, a rapid erythropoietic recovery was observed, whereas the restoration of the granlocytic compartment was impaired. It was concluded that: 1) lasat mice depict a normal hematopoiesis in spite of the congenital absence of the thymus and the spleen; 2) bone marrow stem cells may be defective when administered to lethally irradiated hosts; and 3) the athymic status predominates over the asplenic one.

Animals↗
PubMed1978

Cytotoxicity of a factor from normal and abnormal human spleens for allogenic leukemia cells.

A search for an endogenous cytotoxic factor (ECF) was made by analyzing 103 spleens from normal humans and patients suffering from hematopoietic malignancies, solid tumors, inflammatory diseases, and congestive and hyperplastic splenomegalies. A highly purified ECG was obtained by a combination of gel filtration and ion-exchange column chromatography. The factor is a low-molecular-weight (less than 2,000) substance and is probably a peptide or peptide-nucleotide complex. The biologic activity of EC was assayed on myelogenous and lymphatic leukemia cells of human origin. The spleens from normal individuals produced and/or stored the largest quantity of the ECF. The amount of ECF extractable from the pathologic spleen was drastically diminished regardless of the disease or therapeutic regimen. The ECF was significantly more cytotoxic for lymphatic than for myelogenous leukemia cells.

Anemia↗
PubMed1977

Characterization of an antigen from the myelogenous leukemia cell line K-562.

A protein was solubilized from the myelogenous leukemia cell line K-562 WITh 3 M KCl that specifically inhibited the antibody-dependent, complement-mediated cytolysis of 51Cr-labeled K-562 cells by a monkey antiserum to K-562. When the crude 3 M KCl extract uas fractionated with ammonium sulfate, an eightfold increase in specific activity (U inhibition/mg protein) resulted. This purified fraction migrated as a single protein band after polyacrylamide gel electrophoresis (PGE) with no detectable carbohydrate or lipid. The molecular weight of the denatured protein determined by sodium dodecyl sulfate-PGE was 77,000, similar to that of the native protein (80,000) determined by Sephadex exclusion chromatography. The protein was stable at pH 6-8, with an apparent isoelectric point between pH 5 and 6. In addition to being irreversibly denatured at pH 5 or less, it was unstable at osmolarities below 0.25 M (NaCl). It was denatured at temperatures of 56 degrees C or above. Normal human peripheral blood leukocytes were extracted similarly with 3 M KCl and fractionated with ammonium sulfate. Neither the crude preparation nor any fraction purified as described for the specific antigen inhibited the cytolytic assay, which indicated at least a quantitative lack of the protein on the surfaces of normal leukocytes.

Ammonium Sulfate↗
PubMed1977

Suppression of human myelosarcoma growth in athymic mice by a primate antiserum.

A primate (Macaca speciosa) antiserum prepared against the human chronic myelogenous leukemia cell line K-562 suppressed the growth of the human myelosarcomas in nude mice. The ip administration of 0.5 ml of immune serum plus 0.5 ml of guinea pig complement, starting 7 days after sc tumor transplantation, resulted in a fourfold to fivefold decrease in tumor weight at 15 days when compared to nude mice given pre-immune serum plus complement or complement alone. Whereas the other two groups experienced an exponential increase in tumor volume at 7-9 days after tumor transplantation, the immune serum-treated mice remained in a "lag" phase of tumor growth during which the tumor volume neither increased nor decreased substantially. Histopathologic studies revealed various degrees of tumor alterations ranging form focal hydropic cellular degeneration to massive coagulation necrosis. The incorporation of tritiated thymidine into the tumors was also markedly diminished in the mice given immune serum.

Animals↗
PubMed1977

Hematopoiesis in hereditarily athymic mice.

Hematopoiesis was studied in hereditarily athymic (nude) mice and athymic mice given congeneic thymus cells. Athymic and reconstituted mice had mild anemia which resulted from both hypoplasia of the bone marrow erythrocytic series and decreased iron incorporation in erythroid precursors. Untreated nude mice had hypoplastic marrows due to decrease of both erythrocytic and lymphocytic precursors. The latter was associated with a marked peripheral lymphopenia. Transplantation of thymocytes caused the number of bone marrow and peripheral lymphocytes to return to normal whereas the granulocytic series decreased. Mice reconstituted with thymocytes had marked neutrophilia, eosinophila, and monocytosis compared with either normal or athymic siblings. The number of granulocytic colonies produced by bone marrow cells in agar was very similar in normal and athymic mice with neutrophilia, thus reflecting a normal functioning granulocytic series in a marrow with decreased lymphocytic and erythrocytic cells. The transplantation of thymocytes into athymic mice had no effect on the number of colonies produced by bone marrow cells and the number of spleen colony forming units. It was postulated that maturation of the additional thymocytes permits them to interact with the few endogenous thymocyte precursors present in the nude mice for promotion of bone marrow erythrocytic and lymphocytic proliferations. Alternatively, mature thymocytes may produce factors that were responsible for the effect on lymphoid and erythroid cells.

Animals↗
PubMed1976

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↗