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Biomedical subjects

A Luz

Publications and source records attributed to A Luz.

At least 73 records · Page 4Linked to original sources

Acidophilic macrophage pneumonia in laboratory mice.

Acidophilic macrophage pneumonia, characterized by an accumulation of characteristic crystalloid-laden alveolar macrophages, was seen in 30/7,500 NMRI, 7/600 T x HT, 2/100 C57BL and in no cases of 1,500 CBA and 1,100 BALB/c mice. Histologically, there was a focal accumulation of large numbers of eosinophilic macrophages, generally associated with granulocytes. Macrophages could be mononucleate or multinucleate and had a crystalline cytoplasm. Free-lying crystals were sometimes observed. Ultrastructurally, macrophages had a cytoplasmic accumulation of needle-shaped and rhomboidal crystals, often showing a clear lattice structure with a repeat of 3-5 nm. The crystalloid inclusions may be derived from the breakdown products of granulocytes and appear similar to inclusions in macrophages in other parts of the hematopoietic system. That these inclusions are probably derived from eosinophils is based on the appearance within macrophages of structures resembling eosinophil granules at various stages of degradation and the similarity between the lattice repeat of the crystalloids and that of the crystalline core of the eosinophil granule. The crystalloid inclusions may be related to the Charcot-Leyden crystals found in human beings.

Age Factors↗

Osteosarcoma risk after simultaneous incorporation of the long-lived radionuclide 227Ac and the short-lived radionuclide 227Th.

The effect of injection of 1.85 kBq/kg of the long-lived radionuclide 227Ac on the induction of osteosarcomas in female NMRI mice by different dose levels (18.5, 74, and 185 kBq/kg) of the short-lived radionuclide 227Th was investigated. The highest absolute osteosarcoma incidence was observed with the highest doses of 227Th. Addition of 227Ac resulted in an additional osteosarcoma incidence only at the lowest dose of 227Th and did not affect the osteosarcoma incidence resulting from higher doses of 227Th. The longest times to tumor appearance were observed with 227Ac alone. The latent period in two different age groups (4 weeks and 10-12 weeks) appeared to be similar following injection with combined doses of 227Th and 227Ac but different after injection of each radionuclide alone.

Actinium↗

Computer-assisted imaging cytometry of nuclear chromatin reveals bone tumor virus infection and neoplastic transformation of adherent osteoblast-like cells.

Established osteoblast-like (OB) cells infected with the bone tumor-inducing C-type retrovirus OA MuLV remained nontumorigenic over 104 cell culture passages. DNA histograms revealed a new cell population with a stem line peak at 5c. A second OA MuLV-infected OB cell line underwent neoplastic transformation with increasing passage level. These cells showed diffuse aneuploidy. Stepwise linear discriminant analysis of the chromatin structure of control, OA MuLV-infected, and FBR osteosarcoma virus-transformed cell lines resulted in various levels of discrimination ranging between 79.6% for control cells versus nontumorigenic OA MuLV-infected cells, and 96.6% for nontumorigenic OA MuLV-infected cells versus FBR osteosarcoma virus-transformed cells. OA MuLV-infected tumorigenic cells and FBR osteosarcoma virus-transformed cells were discriminated at a 93.6% level.

Animals↗

Sudden outbreak of a leukemia-like lesion in female CBA mice after repeated injections of 5-azacytidine.

A total of 11 i.p. injections of 1 mg/kg 5-azacytidine given within 21 weeks induced a sudden outbreak of a leukemia-like disease in female CBA mice about 2 weeks after the last injection. The outbreak of disease was highly synchronous; 68% of animals who had survived the treatment period succumbed within a period of 5 days, 2/3 of them on a single day. The lesion had a characteristic form commonly presenting as a result of hemorrhagic effusion in the thoracic and/or abdominal cavities, associated with diffuse infiltration of lymphatic and fatty tissue by lymphoblasts. It appears that a critical combination of factors was responsible for the unexpected appearance of the lesion. Female BALB/c mice treated identically were not affected. The factors indicating that the lesion was induced by an epigenetic mechanism are discussed.

Animals↗

Endogenous murine leukemia viruses: frequency of radiation-activation and novel pathogenic effects of viral isolates.

Female C57BL/6 and BALB/c mice were injected i.p. with 0.06 microCi/kg or 0.5 microCi/kg of the short-lived alpha-emitting radionuclide 224radium at 3-day intervals. Infectious N-ecotropic XC+, and xenotropic C-type retroviruses were activated in several tissues in both strains. In C57BL/6 mice the activation of ecotropic and xenotropic virus was dose-dependent as observed 4 weeks after the start of irradiation. In BALB/c mice a few animals showed activation of ecotropic virus after four weeks of irradiation. The expression of xenotropic virus was similar in irradiated mice and controls. Viral antigen, indicative for viraemia, was not detected in irradiated or control animals. Antiviral antibodies were found in both control and irradiated mice but higher titers were found in the irradiated mice. Bone tissue-derived N-tropic XC+ virus isolates were found to be non-oncogenic in newborn mice of the parental strain. In contrast, the same virus isolates induced a novel pattern of disease, such as osteopetrosis and osteomas together with malignant lymphomas in NMRI mice. The data indicate that the pattern of endogenous murine leukemia virus activation by internal alpha-irradiation is dependent on the dose rate, and on the genetics of the mouse strain.

Animals↗

Establishment and characterization of osteogenic cell lines from a spontaneous murine osteosarcoma.

Five clonal cell lines were established from a spontaneous BALB/c mouse osteosarcoma, and characterized. Four of these lines showed some similarities in morphology, in vitro growth properties, production of collagenous and noncollagenous extracellular matrix proteins and osteogenic differentiation. The cells formed colonies with characteristic differences in size and morphology in soft agar, and osteogenic sarcomas and metastases in syngeneic mice after transplantation. Ultrastructurally, cells in the transplant tumours showed marked osteogenic features. There were no osteoclast-like cells. The fifth cell line had somewhat different characteristics. All five lines expressed infectious endogenous murine leukemia viruses. Increased c-myc protoon-cogene expression was found in one cell line and c-fos expression at different levels in all lines. There was only very low expression of c-Ha-ras and no expression of c-Ki-ras and c-sis. DNA analysis showed the presence of newly acquired proviral genomes integrated at different sites in the cellular DNA. The results show that distinct osteogenic neoplastic subclones can be obtained from a primary mouse osteosarcoma. Although the clones exhibited an appreciable morphological, functional, and molecular diversity they retained the basic pathogenic properties of the tumour from which they were derived.

Alkaline Phosphatase↗

Retrovirus-induced osteopetrosis in mice. Effects of viral infection on osteogenic differentiation in skeletoblast cell cultures.

Newborn female strain NMRI mice were injected with a mouse retrovirus (OA MuLV) known to induce osteopetrosis. Primary skeletoblast cell cultures were established from humeri and calvaria of 3-day-old, 7-day-old, and 28-day-old animals. Infectious ecotropic MuLV was found in all humerus cultures from infected animals and in 7-day and 28-day calvaria cell cultures. Levels of alkaline phosphatase activity were markedly higher in cultures of calvaria and humeri from infected mice than in those from controls. In vitro infection of undifferentiated periosteal cells was followed by a decrease in cell growth and an increase in alkaline phosphatase activity. In contrast, differentiated osteoblast-like cells were barely susceptible to OA MuLV infection, and the virus did not influence their cell growth or differentiation. Electron-microscopic studies of skeletal tissue from infected old osteopetrotic mice showed virus particles associated with and budding from osteocytes and accumulated in devitalized osteocyte lacunae. The results indicate that progenitor cells of the osteoblastic lineage represent the target cells for OA MuLV in bone tissue, that virus infection induces an increase in osteoblastic activity, and that infected cells produce virus until full development of the disease.

Animals↗

Activation and biological properties of endogenous retroviruses in radiation osteosarcomagenesis.

The activation of endogenous retroviruses (MuLV) by internal irradiation and the presence of activated retroviruses in radiation-induced murine osteosarcomas as well as their biological properties in vivo and in vitro were studied. Ecotropic and xenotropic MuLV were expressed dependent on the radiation dose in spleen, bone marrow and bone tissues of C57Bl/6 mice after 224Ra treatment. Radiation-induced osteosarcomas of BALB/c, C57Bl/6 and C3H X 101/F1 mice harboured infectious ecotropic and/or xenotropic viruses whereas in osteosarcomas of NMRI mice predominantly virus protein could be detected. In about 50% of the radiation-induced osteosarcomas of BALB/c mice an amplification of ecotropic proviruses could be detected. This was not found in clonally grown cells from non-tumorous tissues. MuLV from radiation-induced osteosarcomas induced osteopetrosis, osteomas and lymphomas after infection of newborn NMRI mice. In differentiating bone tissue the viruses were found to infect predominantly osteoblast precursor cells suggesting that virus infection results in increased growth and metabolic activity of these cells, which may be a possible mechanism for their pathogenic action in bone tissues.

Animals↗

Incidence, morphology, and ultrastructure of spontaneous thymoma--the most common neoplasm in W/Nhg rats.

Spontaneous thymoma was observed with an incidence of 97 and 36% in female and male rats, respectively, from an inbred Wistar/Neuherberg strain (W/Nhg). The thymomas often caused dyspnea and were occasionally the direct cause of death. The neoplasms resembled human thymomas and showed a variable cell composition, ranging from mainly lymphocytic to mainly epithelial. The detailed ultrastructural findings are described and compared with those in other rat thymomas and in human thymomas. A characteristic feature of all dividing lymphocytes was the presence of often multilayered, confronting cisternae. As in more than 50% of human thymomas, W/Nhg rat thymomas were not associated with myopathies or any other possibly autoimmune diseases. They may thus offer a useful model for the study of thymoma without associated parathymic syndromes.

Age Factors↗

Antigens and circulating immune complexes related to the primate retroviral glycoprotein SiSVgp70. Indicators of early mortality in human acute leukemias and chronic myelogenous leukemias in blast crisis.

Human sera contain antigens and also circulating immune complexes that are related to the primate retroviral envelope glycoprotein gp70 of simian sarcoma/simian sarcoma associated virus (SiSV) and of gibbon ape leukemia virus (GaLV). SiSVgp70 related antigens (AG) and immune complexes (IC) are detected both in leukemic and in nonleukemic sera. In a further analysis of these data, the prognostic significance of SiSVgp70 related AG and IC in leukemic patients was examined. The data show that the presence of SiSVgp70 related AG and IC indicates an unfavorable clinical course and a shorter survival time in acute leukemias (AL) and in chronic myelogenous leukemia in blast crisis (CML-BC). Survival data of 56 of 64 patients tested were analyzed (38 patients with AL and 18 patients with CML-BC). Patients with AL whose sera were positive for SiSVgp70 related AG and IC had a median survival time of 9.5 months after diagnosis versus 16 months for patients negative for such AG and IC. This difference in survival time was more pronounced for patients with acute nonlymphocytic leukemia (ANLL) (6.5 versus 19 months). The difference in survival between SiSVgp70 related AG- and IC-negative and positive groups as tested by life table analysis (log-rank test) is significant (P less than 0.05). Patients with AL of the AG- and/or IC-positive group had fewer complete remissions. Patients who had no remissions belong to the AG- and/or IC-positive group (P = 0.06). Patients with CML-BC whose sera were positive for SiSVgp70 related AG and/or IC had a median survival time of 2 months after diagnosis versus 7 months for patients with sera negative for such AG and IC. As tested by log-rank test, survival curves between the two groups are significantly different (P less than 0.05). These findings suggest that SiSVgp70 related AG and IC may play an important role in the course of acute leukemia and can provide useful prognostic information.

Acute Disease↗

Excretion of modified nucleosides during development of malignant lymphomas in mice after whole body irradiation.

During x-ray-induced development of malignant lymphomas in mice their urinary excretion of eight modified nucleosides was monitored and the values were compared to the results of the histological examination of the animals at time of their sacrifice. It was found that the pathologically augmented excretion of modified nucleosides begins as much as several weeks before the malignant lymphomas can be diagnosed clinically. Thus some mice had increased levels of modified nucleosides even 10 weeks before sacrifice, though at the time of sacrifice the histological investigation revealed only some small foci of reticulum cell neoplasm in their spleen. It is therefore stressed that the usefulness of the determination of urinary modified nucleosides as an early noninvasive screening test for cancer in man and as an in vivo carcinogenicity test should be evaluated.

Animals↗

Incidence of radiation lymphomas in C57BL/6 mice is not promoted after intraperitoneal treatment with the phorbol ester tetradecanoylphorbol acetate.

Female C57BL/6 mice, given 4 X-ray irradiations each with 1.7 Gy, according to H.S. Kaplan and M.S. Brown (J. Natl. Cancer Inst., 13 (1952) 185-192) developed lethal lymphomas in more than 90%, 270 days after irradiation. Intraperitoneal application of tetradecanoylphorbol acetate (TPA), 30 ng/g, twice weekly for 240 days had no influence on survival of the animals and incidence of the malignant lymphomas.

Animals↗