PubMed Health⌕ Search

Biomedical subjects

L Kubai

Publications and source records attributed to L Kubai.

15 recordsLinked to original sources
PubMed1993

A ribonuclease inhibitor expresses anti-angiogenic properties and leads to reduced tumor growth in mice.

Our experiments were designed to determine whether recombinant ribonuclease inhibitor (RNasin) could inhibit angiogenesis and reduce tumor growth in adult mice. We used the Fajardo disc angiogenesis assay as the primary means of measuring new blood vessel growth. This assay measures the penetration of cells into a polyvinyl alcohol sponge with a central core of ELVAX-coated sponge containing test substances. Cell penetration was reduced to 29.3% of control (phosphate-buffered saline; heat-inactivated RNasin) values. Endothelial cell influx was measured by lectin staining and confirmed by culturing cells isolated from sponges by collagenase treatment. RNasin also reduced the augmented reaction evoked by either basic fibroblast growth factor (bFGF) or sodium orthovanadate. To confirm the anti-angiogenic activity of RNasin, Hydron-coated polyvinyl sponges containing bFGF or bFGF plus RNasin were implanted into adult mouse corneas. bFGF induced a strong angiogenic response that was almost completely inhibited by RNasin. RNasin-containing ELVAX-coated sponges implanted subcutaneously underneath an intradermal inoculum of C755 mammary tumor cells caused significant reduction in tumor growth (P < 0.005). The antitumor effect of RNasin correlated with its effect on tumor-induced neovascularization, suggesting that the ability of RNasin to affect tumor growth was due to its ability to inhibit angiogenesis.

Adenocarcinoma↗
PubMed1992

An immune model of beryllium-induced pulmonary granulomata in mice. Histopathology, immune reactivity, and flow-cytometric analysis of bronchoalveolar lavage-derived cells.

BACKGROUND: Beryllium compounds can cause acute and chronic lung injury in humans. Although models of chronic granulomatous lung disease have been established in various animal species, a murine model of beryllium-induced chronic lung disease has not been established. EXPERIMENTAL DESIGN: Beryllium was introduced intratracheally either as a soluble salt (BeSO4) or in particulate form (BeO). Various preimmunization protocols were used to enhance immune-mediated pulmonary changes. Cells obtained by bronchoalveolar lavage (BAL) were analyzed using flow cytometry, and the observations correlated with in vitro immune responses and with lung histopathology. RESULTS: Histologic changes were consistently found in mice preimmunized with BeSO4.4H2O plus syngeneic serum. Addition of complete or incomplete Freund's adjuvant to the preimmunization protocol was not necessary to induce granulomatous changes. BAL showed a significant increase in lymphocytes at 2, 4, and 8 weeks after intratracheal BeSO4. Approximately one-third of BAL lymphocytes expressed the gamma/delta T lymphocyte receptor at 2 weeks; at 4 weeks the lymphocytes were predominantly Thy1+, L3T4+ (CD4+) and expressed only the alpha/beta T lymphocyte receptor. Only BAL lymphocytes from mice preimmunized with BeSO4/serum and challenged with BeSO4/serum showed significant in vitro proliferation in response to BeSO4. Macrophage activation antigens (Mac-2, Mac-3) were expressed only during the acute inflammatory phase (2 weeks) whereas increased expression of a monocyte/macrophage antigen (Mac-1) remained elevated beyond the inflammatory period in some instances. Attempts to induce similar lesions in BALB/c and C57BL6/J mice were unsuccessful. Genetic differences at the H-2 major histocompatibility complex gene complex may account for the differential responses to BeSO4 among various mouse strains. A single exposure to BeO also induced histopathologic changes in the lung which correlated with BAL cellularity, but these changes were only observed 8 months after exposure and did not proceed to frank granulomas. CONCLUSIONS: A murine model of granulomatous lung disease may prove useful in understanding the genetic and immunologic factors that determine the response to beryllium. The animal model may also have implications for pulmonary sarcoidosis, a disease of unknown cause(s), whose disease manifestations and BAL profiles are difficult to distinguish clinically and pathologically from chronic beryllium disease.

Animals↗
PubMed1987

In vitro differentiation of mouse embryonic yolk sac cells.

The embryonic yolk sac is the first site in the mammalian embryo in which cells are found that can carry out cell-mediated immune functions, yet the relation of cells of this primitive hematopoietic organ to the development of the mature immune system has not been established. We have initiated a series of experiments to determine the potential of cells of the mouse yolk sac to differentiate in vitro, in order to get an insight into the development of immunocompetence in this primary population of hematopoietic stem cells. The present paper describes the conditions promoting stem-cell differentiation and provides an initial characterization of cell surface phenotypes of the cell lineages established in vitro. Yolk sac cells obtained from 10- to 13-day mouse embryos were maintained in culture for more than 18 months, giving rise to a variety of cell types belonging to the hematopoietic lineages and culminating in the establishment of long-term cell lines. Supernatants of secondary mixed leukocyte cultures were found to be an effective source of growth factors promoting the initial differentiation as well as the maintenance of these cells. Flow-cytometric analysis showed that, in contrast to freshly obtained yolk sac cells, which had no detectable Thy 1 antigen, cells expressing significant levels of Thy 1 were obtained after 1 week or more of culture. Ly1 and Lyt 2 antigens were detected only rarely and the L3T4 (GK 1.5) antigen was never expressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

A new source of embryonic lymphocytes in the mouse.

The source of stem cells within the early mammalian embryo has not been identified. The yolk sac, once thought to provide the early stem cells in birds, is now seen more as a primitive effector organ capable of allorecognition, natural cytotoxic reactions and elaboration of cytokines. In lower vertebrates the source appears to be within a region delineated by the anterior limbs, foregut and mesonephros. That region defines the boundaries of the developing omentum, a fold in the peritoneum. As the omentum is known to develop lymphoid cells postnatally we have now examined the omental rudiment for the presence of lymphoid cell precursors. Our experiments provide evidence that the presumptive omentum of the 13-day mouse embryo is capable of histiotypic differentiation into a reticular organ containing a significant number of Thy 1+ lymphocytes, which suggests that the omentum may represent a new primary lymphoid organ in the mouse.

Animals↗
PubMed1982

Tumor-induced neovascularization in the mouse eye.

Tumor fragments implanted in the mouse cornea induce a neovascular reaction characterized by the penetration of new blood vessels into the avascular cornea that ultimately reach the tumor to permit its further rapid growth. A method to achieve angiogenesis in the mouse cornea was studied, as well as the histologic and gross manifestations of the neovascular reaction and the effect of tumor cells or host irradiation on the observed angiogenic response. Sequential stages of tumor-induced neovascularization are described and documented for sarcoma 180- and C755 mammary adenocarcinoma-induced angiogenesis. A number of distinct processes of the angiogenesis response to tumors are discussed which suggest that several families of angiogenesis-inducing factors may mediate each of these processes. The importance of the development of a mouse model for the study of angiogenesis is stressed.

Adenocarcinoma↗
PubMed1980

Regional differences in the growth of skin transplants.

We have previously reported that marked differences exist in the relative growth rate of tumors transplanted i.d. or s.c. into different regions of the mouse trunk. The present experiments were undertaken to determine whether or not these regional differences applied uniquely to tumor tissue or whether or not there existed a more basic underlying principle influencing normal tissue growth as well. As a test system we used skin transplants between histocompatible C57BL/6J and C57BL/6-c2J mice. Grafts were placed middorsally in the thoracic or lumbar region and compared for rate of healing in, skin retraction, growth, and hair formation. A marked differential in the establishment and growth of skin grafts was seen: anteriorly placed skin transplants uniformly resulted in larger grafts than did similar transplants placed more posteriorly. Our experiments suggest that there are basic physiologically differences between the more anterior and posterior regions of the trunk that are reflected in the relative growth and maintenance of tissue transplants. As yet we have no clear indication of what factors contribute to this anteroposterior differential.

Animals↗
PubMed1980

Feto-maternal histoincompatibility and placental blood flow.

1. We have designed experiments aimed at resolving some of the controversy concerning the effect of histoincompatibility on the development of the fetus and its placenta. 2. Experiments included the generation of pregnancies in which H-2 compatible and H-2 histoincompatible embryos were simultaneously present. Genetic markers (Brachyury and Kink) were used to facilitate determination of the H-2 haplotype. Additional strain combinations were used to analyse the role of non-H-2 differences. 3. In addition to determining fetal and placental weights, blood flow to the placenta was measured by use of radioisotope-labelled microspheres introduced into the arterial circulation. 4. Under the conditions of our experiments we have failed to detect differences in fetal weight, in placental weight, or in placental blood flow. 5. Thus we support the increasingly prevalent view that histo-incompatibility does not necessarily lead to changes in placental or fetal weight, and we add the additional finding that placental blood flow also is not significantly altered as a result of feto-maternal incompatibility.

Animals↗
PubMed1976

Studies on the maturation of immune responsiveness in the mouse. II. Role of the spleen.

Experiments were designed to investigate the role of the spleen in the development of the murine immune system. By using mice splenectomized within 24 hr of birth, as well as mice with a hereditary, congenital absence of the spleen, the primary immune response to sheep erythrocytes was examined. The immunocompetence of lymph node cells from spleenless or control mice was assessed in vitro, in organ and in cell suspension cultures, and in vivo, by transfer into lethally irradiated syngeneic recipients followed by antigenic stimulation. The immunologic capacities of thymus and bone marrow cells were similarly tested by injection separately or in combination into irradiated syngeneic mice. Lymph node cells from spleenless animals appeared fully competent both in vitro and in transfer experiments. Neither neonatal splenectomy nor congenital absence of the spleen significantly reduced the capacity of bone marrow or thymus cells to participate in the immune response to sheep erythrocytes.

Aging↗
PubMed1976

Angiogenesis induction by tumors, embryonic tissues, and lymphocytes.

Although it is well established that tumors can induce endothelial cell mitosis and angiogenesis leading to extensive neovascularization, little is known concerning the spectrum of normal cells or tissues that may have similar inductive capabilities. A variety of developmentally active tissues were tested: mouse embryonic organ rudiments, mouse and rabbit trophoblast and placenta, and blastemal fragments obtained from regnerating deer antlers. Assays for angiogenesis included grafts made to the chorioallantoic membrane of chick embryos and grafts placed intracorneally in adult rabbit eyes. Virtually all of these test tissues were negative, the only exceptions being some antler grafts and some grafts obtained from metanephric tubules of the embryonic mouse kidney.

Angiogenesis Inducing Agents↗
PubMed1975

Tumor-induced angiogenesis: lack of inhibition by irradiation.

The effect of irradiation of tumors on their ability to induce vascular responses (angiogenesis) was studied. Rat Walker carcino-sarcoma 256, rabbit V2 carcinoma, mouse (C57B1) melanoma and mouse (129) teratoma (OTT 6050, 100K) were irradiated with up to 5000R, then grafted either to the chicken chorioallantoic membrane or intracorneally into adult rabbits to assess competence to provoke angiogenesis. For all tumors and both assay systems the results were similar: irradiation did not interfere with tumor-induced vascular responses.

Angiogenesis Inducing Agents↗