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Preaxial Polydactyly in Sost/Sostdc1 Double Knockouts

Description: In the United States, {approx}5% are born with congenital birth defects due to abnormal function of cellular processes and interactions. Sclerosteosis, a rare autosomal recessive disease, causes hyperostosis of the axial and appendicular skeleton, and patients present radial deviation, digit syndactyly, nail dysplasia, and overall high bone mineral density. Sclerosteosis is due to a loss of function of sclerostin (Sost). Sost is a Wnt (abbrev.) antagonist; when mutated, nonfunctional Sost results in hyperactive osteoblast activity which leads to abnormal high bone mass. Previous studies have shown that Sost overexpression in transgenic mice causes reduced bone mineral density and a variety of limb phenotypes ranging from lost, fused, and split phalanges. Consistent with clinical manifestations of Sclerosteosis, Sost knockout mice exhibit increased generalized bone mineral density and syndactyly of the digits. Sostdc1 is a paralog of Sost that has also been described as an antagonist of Wnt signaling, in developing tooth buds. Unlike Sost knockouts, Sostdc1 null mice do not display any limb abnormalities. To determine if Sost and Sostdc1 have redundant functions during limb patterning, we examined Sost; Sostdc1 mice determined that they exhibit a novel preaxial polydactyly phenotype with a low penetrance. LacZ staining, skeletal preparations, and in situ hybridization experiments were used to help characterize this novel phenotype and understand how this phenotype develops. We find Sost and Sostdc1 to have complementary expression patterns during limb development, and the loss of their expression alters the transcription of several key limb regulators, such as Fgf8, Shh and Grem.
Date: July 29, 2011
Creator: Yee, C M; Collette, N M & Loots, G G
Partner: UNT Libraries Government Documents Department

OSTEOBLAST ADHESION OF BREAST CANCER CELLS WITH SCANNING ACOUSTIC MICROSCOPY

Description: Breast cancer frequently metastasizes to the bone. Upon colonizing bone tissue, the cancer cells stimulate osteoclasts (cells that break bone down), resulting in large lesions in the bone. The breast cancer cells also affect osteoblasts (cells that build new bone). Conditioned medium was collected from a bone-metastatic breast cancer cell line, MDA-MB-231, and cultured with an immature osteoblast cell line, MC3T3-E1. Under these conditions the osteoblasts acquired a changed morphology and appeared to adherer in a different way to the substrate and to each other. To characterize cell adhesion, MC3T3-E1 osteoblasts were cultured with or without MDA-MB-231 conditioned medium for two days, and then assayed with a mechanical scanning acoustic reflection microscope (SAM). The SAM indicated that in normal medium the MC3T3-E1 osteoblasts were firmly attached to their plastic substrate. However, MC3T3-E1 cells cultured with MDA-MB-231 conditioned medium displayed both an abnormal shape and poor adhesion at the substrate interface. The cells were fixed and stained to visualize cytoskeletal components using optical microscopic techniques. We were not able to observe these differences until the cells were quite confluent after 7 days of culture. However, using the SAM, we were able to detect these changes within 2 days of culture with MDA-MB-231 conditioned medium
Date: March 1, 2005
Creator: Miyasaka, Chiaki; Mercer, Robyn R.; Mastro, Andrea M. & Telschow, Ken L.
Partner: UNT Libraries Government Documents Department

Clonal analysis of bone marrow and macrophage cultures

Description: To establish lineages that can be used to study their functional heterogeneity, the proliferation and differentiation of bone marrow derived mononuclear phagocytes and the lineages derived from them were studied. 28 references, 7 figures, 5 tables. (ACR)
Date: January 1, 1984
Creator: Stewart, C.C.; Walker, E.B.; Johnson, C. & Little, R.
Partner: UNT Libraries Government Documents Department

Functionalization of Hydrogen-free Diamond-like Carbon Films using Open-air Dielectric Barrier Discharge Atmospheric Plasma Treatments

Description: A dielectric barrier discharge (DBD) technique has been employed to produce uniform atmospheric plasmas of He and N2 gas mixtures in open air in order to functionalize the surface of filtered-arc deposited hydrogen-free diamond-like carbon (DLC) films. XPS measurements were carried out on both untreated and He/N2 DBD plasma treated DLC surfaces. Chemical states of the C 1s and N 1s peaks were collected and used to characterize the surface bonds. Contact angle measurements were also used to record the short- and long-term variations in wettability of treated and untreated DLC. In addition, cell viability tests were performed to determine the influence of various He/N2 atmospheric plasma treatments on the attachment of osteoblast MC3T3 cells. Current evidence shows the feasibility of atmospheric plasmas in producing long-lasting variations in the surface bonding and surface energy of hydrogen-free DLC and consequently the potential for this technique in the functionalization of DLC coated devices.
Date: December 28, 2007
Creator: Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Instituto de Materiales de Madrid, C.S.I.C., Cantoblanco, 28049 Madrid, Spain; Instituto de Quimica-Fisica"Rocasolano"C.S.I.C., 28006 Madrid, Spain; Mahasarakham University, Mahasarakham 44150, Thailand; CASTI, CNR-INFM Regional Laboratory, L'Aquila 67100, Italy; SUNY Upstate Medical University, Syracuse, NY 13210, USA et al.
Partner: UNT Libraries Government Documents Department

Sorting of a murine granulocytic progenitor cell by use of laser light scattering measurements

Description: Multiangle light-scattering measurements provided a useful basis for analysis and separation of bone marrow cell suspensions. Six to eight major subpopulations of cells could be distinguished by simultaneous measurements of forward and 90/sup 0/ light-scattering, which is more than with any other known cell separation method. The observation that CFU-c were found in only one of these subpopulations confirms the conclusions that CFU-c are a homogeneous population of a single cell type.
Date: January 1, 1977
Creator: Visser, J.W.M.; Cram, L.S.; Martin, J.C.; Salzman, G.C. & Price, B.J.
Partner: UNT Libraries Government Documents Department

Growth regulation by macrophages

Description: The evidence reviewed here indicates that macrophages, either acting alone or in concert with other cells, influence the proliferation of multiple types of cells. Most of the data indicate that these effects are mediated by soluble macrophage-elaborated products (probably proteins) although the role of direct cell-to-cell contacts cannot be ruled out in all cases. A degree of success has been achieved on the biochemical characterization of these factors, due mainly to their low specific activity in conditioned medium and the lack of rapid, specific assays. Understanding the growth-regulating potential of macrophages is an important and needed area of research.
Date: January 1, 1982
Creator: Wharton, W.; Walker, E. & Stewart, C.C.
Partner: UNT Libraries Government Documents Department

Flow cytometric measurements of cell surface phenomena

Description: The study of cell surface phenomena by flow cytometry has been pursued by several groups. These studies have produced new insights into a variety of areas of biology. However, the capabilities of flow systems have not been fully exploited. A technique for discriminating between surface and volume fluorescence is proposed along with a method to quantitate cap formation in lymphocytes.
Date: January 1, 1979
Creator: Jett, J.H.
Partner: UNT Libraries Government Documents Department

Models for the interaction between cells of the immune system

Description: The following topics are discussed: mathematical models of cell-to-cell interactions; role of cell-to-cell contacts in regulating immune responses; cell-to-cell binding; the strength of specific bonds; rate of bond formation; and effects of binding on cell behavior. It is concluded that receptor accumulations are to be expected in areas of cell--cell contact. Gross alterations in membrane properties in these contact caps may result. (HLW)
Date: January 1, 1978
Creator: Bell, G.I.
Partner: UNT Libraries Government Documents Department

Bovine lymphocytic leukemia: studies of etiology, pathogenesis, and mode of transmission. Progress report No. 19, June 1978-June 1979

Description: Bovine leukemia is believed to be caused by an oncogenic RNA virus designated bovine leukemia virus (BLV). The presence of BLV particles in lymphocyte cultures from leukemic cattle and cattle with a persistent lymphocytosis has been consistentily demonstrated. Concentrated, cell free, BLV preparations were used to inoculate 12 late stage bovine fetuses (in utero) and two newborn calves. Current studies involve extensive monitoring of these inoculated animals to detect precancerous changes and obtain a detailed description of the events preceding the development of lymphosarcoma. Ongoing monitoring studies will provide a complete record of all changes in the various leukemia associated parameters. We will then be able to detail when, in what sequence, and to what extent each parameter changes in the course of lymphosarcoma development. Fourteen animals were successfully inoculated during the study. Eleven remain alive, and comprise the current monitoring program. All eleven of these animals are definitely infected with BLV, and in nine the infection has substantially progressed with respect to the parameters being monitored. In addition to transmission and monitoring studies, various lymphocyte subpopulations were examined to determine which cell type(s) are involved in the pathogenesis of bovine lymphosarcoma. These studies have conclusively established that B-lymphocytes are the target cells for BLV infection and that they carry the morphologic nuclear abnormality associated with this disease.
Date: July 1, 1979
Creator: Sorensen, D.K.
Partner: UNT Libraries Government Documents Department

Applications of optimal control theory to immunology

Description: When an animal is challenged by a foreign substance which promotes an immune response, certain cells within the animal begin dividing, secreting antibody molecules, and differentiating into more specialized cell types. Optimal control theory is applied to ascertain the best strategy available to the immune system in allocating its cells. By examining a variety of mathematical models for cell populations and their antibody production, it is found that the optimal strategy of bang-bang control is robust. Experimental evidence which supports such strategies is also discussed.
Date: January 1, 1977
Creator: Perelson, A.S.
Partner: UNT Libraries Government Documents Department

(In vivo mutagenicity and clastogenicity of ionizing radiation in nuclear medicine)

Description: The overall goals of our research remains to investigate the mutagenic and clastogenic effects of exposure to low levels of ionizing radiation in human lymphocytes. We are studying hospital patients referred to a nuclear medicine department for diagnostic cardiac imaging and nuclear medicine technologists who administer radionuclides.
Date: January 1, 1989
Partner: UNT Libraries Government Documents Department

Regulation of hemopoiesis: inhibitors and stimulators produced by a murine bone marrow stromal cell line (H-1)

Description: A murine cell line (H-1) probably derived from the adventitial reticular cell has been isolated and preserved. This line produces: (1) CSF; (2) a labile inhibitor of CFU-c proliferation with preferential action on granulopoiesis; (3) PGE; (4) proliferation inhibitors of BFU-E and GEMM; and (5) suppression of entry of CFU-S into DNA synthesis in vitro. It is postulated that the adventitial reticular cell (ARC) may play a major regulatory role in hemopoiesis through intramedullary production of the factors described. The nature of the signals that activate the genes in the ARC which are coded for the factors described is not known.
Date: January 1, 1982
Creator: Cronkite, E.P.; Miller, M.E.; Garnett, H. & Harigaya, K.
Partner: UNT Libraries Government Documents Department

Removal of uv-induced pyrimidine dimers from the replicated and unreplicated DNA of human fibroblasts

Description: Excision repair in uv irradiated human fibroblasts has been examined in portions of DNA replicating after irradiation versus those remaining unreplicated. Two approaches, one using a uv-endonuclease to estimate pyrimidine dimers remaining in DNA, the other using density labeling to measure excision resynthesis, indicate that the extent of repair is the same for both replicated and unreplicated DNA.
Date: January 1, 1978
Creator: Waters, R.
Partner: UNT Libraries Government Documents Department

Pulmonary macrophage and epithelial cells

Description: Separate abstracts were prepared for the 41 papers presented at the conference. Abstracts of two papers have appeared in previous issues of Energy Research Abstracts. (HLW)
Date: January 1, 1977
Creator: Sanders, C.L.; Schneider, R.P.; Dagle, G.E. & Ragan, H.A. (eds.)
Partner: UNT Libraries Government Documents Department

A model for the immune system response to HIV: AZT treatment studies

Description: We use mathematical models to describe the interaction of the immune system with the human immunodeficiency virus (HIV). Our model includes T-lymphocytes and macrophages, cells which can be infected with the virus. Using our model we compare the efficacy of AZT treatments given at different stages of disease progression in order to predict when treatment should be initiated.
Date: January 1, 1993
Creator: Kirschner, D.E. (Vanderbilt Univ., Nashville, TN (United States). Dept. of Mathematics) & Perelson, A.S. (Los Alamos National Lab., NM (United States))
Partner: UNT Libraries Government Documents Department

Mechanisms underlying the redistribution of particles among the lung's alveolar macrophages during alveolar phase clearance

Description: In order to obtain information about the particle redistribution phenomenon following the deposition of inhaled particles, as well as to obtain information about some of the mechanisms that may be operable in the redistribution of particles, lavaged lung free cell analyses and transmission electron microscopic (TEM) analyses of lung tissue and were performed using lungs from rats after they were subchronically exposed to aerosolized dioxide (TiO{sub 2}). TEM analyses indicated that the in situ autolysis of particle-containing Alveolar Macropages (AM) is one important mechanism involved in the redistribution of particles. Evidence was also obtained that indicated that the engulfment of one particle-containing phagocyte by another phagocyte also occurs. Another prominent mechanism of the particle redistribution phenomenon may be the in situ proliferation of particle-laden AM. We used the macrophage cell line J774A.1 as a surrogate for AM to investigate how different particulate loads in macrophages may affect their abilities to proliferate. These in vitro investigations indicated that the normal rate of proliferation of macrophages is essentially unaffected by the containment of relatively high particulate burdens. Overall, the results of our investigations suggest that in situ autolysis of particle-containing AM and the rephagocytosis of freed particles by other phagocytes, the phagocytosis of effete and disintegrating particle-containing phagocytes by other AM, and the in situ division of particle-containing AM are likely mechanisms that underlie the post-depositional redistribution of particles among the lung's AM during alveolar phase clearance. 19 refs., 8 figs., 2 tabs.
Date: January 1, 1991
Creator: Lehnert, B.E.; Oritz, J.B.; Steinkamp, J.A.; Tietjen, G.L.; Sebring, R.J. (Los Alamos National Lab., NM (United States)) & Oberdorster, G. (Rochester Univ., NY (United States))
Partner: UNT Libraries Government Documents Department

Genetic algorithms and the immune system

Description: Using genetic algorithm techniques we introduce a model to examine the hypothesis that antibody and T cell receptor genes evolved so as to encode the information needed to recognize schemas that characterize common pathogens. We have implemented the algorithm on the Connection Machine for 16,384 64-bit antigens and 512 64-bit antibodies. 8 refs.
Date: January 1, 1990
Creator: Forrest, S. (New Mexico Univ., Albuquerque, NM (USA). Dept. of Computer Science) & Perelson, A.S. (Los Alamos National Lab., NM (USA))
Partner: UNT Libraries Government Documents Department

Malignant transformation of human fibroblasts in vitro

Description: Although carcinogens cause human tumors, human cells in culture have not been successfully transformed to malignancy by exposure to carcinogens. It is now recognized that malignant transformation involves multiple changes within a cell and, therefore, successive clonal selection of cells containing such changes must occur. One explanation for the failure to induce in vitro malignant transformation of human cells could be inability to recognize cells that have undergone intermediate changes so as to expand the population, expose the cells a second time, cause further changes, etc. therefore, we transfected finite life span diploid human fibroblists with oncogenes known to be active in cells derived from human fibrosarcomas or effective in transforming animal fibroblasts to determine the phenotypes they produced. Transfection of a sis gene, or an H-, or H-ras oncogene caused the cells to acquire many characteristics of malignant cells, but not to acquire an infinite lift span or become malignant. We recently succeeded in developing an infinite life span human fibroblasts cell strain, designated MSU-1.1, which has a stable, near-diploid karyotype, composed of 45 chromosomes including two marker chromosomes. We have shown-that these cells can be transformed to malignancy by transfection of the H-, K-, or N-ras or the v-fes oncogene. All of the malignant H-, K-, or N-ras transfected derivatives examined have exhibited the stable karyotype of the parental MSU-1.1 cells. We have also found rare spontaneous clonal variants of MSU-1.1 that are malignantly transformed and have shown that malignant variants can also be induced by carcinogen treatment.
Date: January 1, 1991
Creator: McCormick, J.J. & Maher, V.M.
Partner: UNT Libraries Government Documents Department

Expert systems for flow cytometry data analysis: A preliminary report

Description: Flow Cytometry has become an accepted technique in the clinical laboratory for rapid immunophenotyping of patient blood samples. Multiple, fluorescent labeled monoclonal antibodies are used to tag the cells, which are then analyzed one at a time at rates of several thousand cells a second. Patient samples are processed through the flow cytometer at more than one a minute. Clinicians are being overwhelmed by the large amount of data that must be analyzed to provide the information needed to assist in disease diagnosis. An expert system is being developed to assist clinicians in analyzing this multivariate flow cytometry data. The data from each sample are processed by a clustering algorithm, which finds the means of the distinct cell subpopulations in a sample. These mean values of fluorescence are translated into words such as negative,'' dim'' and bright'' and the words are combined into patterns that are matched against the premises on the left hand side of the rules used to identify the disease categories. This is a report of work in progress. 13 refs., 4 figs.
Date: January 1, 1990
Creator: Salzman, G.C. (Los Alamos National Lab., NM (USA)); Stewart, C.C. (Roswell Park Memorial Inst., Buffalo, NY (USA). Lab. of Flow Cytometry) & Duque, R.E. (Norwood Clinic, Birmingham, AL (USA))
Partner: UNT Libraries Government Documents Department

Physiopathology of blood platelets: a model system for studies of cell-to-cell interaction. Progress report, November 1, 1978-October 31, 1979

Description: In this report, we will limit ourselves to the detailed description of four major sections of our research done during the past year: platelet interaction with tumor cells; studies of the interaction of platelets with macrophages; interaction of platelets with vessel walls; and further studies of cyclic nucleotides on stored platelets.
Date: January 1, 1979
Creator: Baldini, M G
Partner: UNT Libraries Government Documents Department

Biological response modifiers

Description: Much of what used to be called immunotherapy is now included in the term biological response modifiers. Biological response modifiers (BRMs) are defined as those agents or approaches that modify the relationship between the tumor and host by modifying the host's biological response to tumor cells with resultant therapeutic effects.'' Most of the early work with BRMs centered around observations of spontaneous tumor regression and the association of tumor regression with concurrent bacterial infections. The BRM can modify the host response in the following ways: Increase the host's antitumor responses through augmentation and/or restoration of effector mechanisms or mediators of the host's defense or decrease the deleterious component by the host's reaction; Increase the host's defenses by the administration of natural biologics (or the synthetic derivatives thereof) as effectors or mediators of an antitumor response; Augment the host's response to modified tumor cells or vaccines, which might stimulate a greater response by the host or increase tumor-cell sensitivity to an existing response; Decrease the transformation and/or increase differentiation (maturation) of tumor cells; or Increase the ability of the host to tolerate damage by cytotoxic modalities of cancer treatment.
Date: October 1, 1991
Creator: Weller, R.E.
Partner: UNT Libraries Government Documents Department

Metastasis

Description: Distant metastasis of primary neoplasms is the main factor that limits the success of antineoplastic therapy. It can be regarded as an early or late event in the neoplastic process, and varies considerably with tumor type. The metastatic potential of a given tumor greatly influences prognosis. Tumor metastasis is not a single neoplastic event, rather, it involves several major steps: invasion of cells from the primary tumor into tissue, and penetration of blood and lymph vessels; release of tumor cell emboli into the circulation; arrest of the emboli in capillary beds of distant organs; invasion of the wall of the arresting vessel, infiltration into adjacent tissue, and multiplication; and growth of vascularized stroma into the new tumor as proliferating tumor cells invade the distant organ. Lodgement and invasion are complex events that are not fully defined. Arrest and lodgement appears to require a thromboembolic event in which the metastatic embolis (1 cell) contacts vascular endothelium and adheres to the wall with thrombis formation following aggregation of platelets and fibrin to the tumor cell(s). Invasion may involve: formation of collagenases by tumor cells; mechanical disruption; chemotactic factors. Metastatic patterns depend on the route of metastasis, tumor type, and target organ (favored soil). In general, carcinomas metastasize via lymphatics and sarcomas via hematogenous routes. Others, melanoma, mast cell tumors, etc., show mixed patterns. This knowledge is important when one is attempting to prognostically stage a tumor, especially when thoracic radiographs are negative. The question of enlarged regional lymph nodes will be discussed in lecture relative to specific tumor types. 4 refs., 1 tab.
Date: October 1, 1991
Creator: Weller, R.E.
Partner: UNT Libraries Government Documents Department