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Sample records for heavy ion-induced mammary

  1. Heavy ion induced permanent damage in MNOS gate insulators

    NASA Astrophysics Data System (ADS)

    Pickel, J. C.; Blandford, J. T., Jr.; Waskiewicz, A. E.; Strahan, V. H., Jr.

    1985-12-01

    Heavy-ion-induced permanent damage in MNOS gate insulators has been investigated using a Cf252 fission source. The electric field and ion LET thresholds for onset of the damage has been characterized. The results are consistent with a thermal runaway mechanism in the silicon nitride layer initiated by a single heavy ion and leading to a permanent high conductivity path through the dielectric layers.

  2. Solutions to heavy ion induced avalanche burnout in power devices

    SciTech Connect

    Wrobel, T.F.; Beutler, D.E.

    1991-01-01

    Silicon power devices fall into two broad categories, bipolar and field effect. Transistors using both of these technologies are often used in satellite applications for power conversion. The present trend is toward integrating power transistors and control electronics on the same chip. In this case, it is the power portion of the chip that is most susceptible to burnout failures, because of it's high voltage operation. Hence, it is important to understand the operational limitations of power transistors when exposed to intense heavy ion and/or dose-rate environments. Reviews of normal breakdown and current induced avalanche breakdown mechanisms in silicon power transistors are presented. We show the applicability of the current induced avalanche model to heavy ion induced burnouts and present solutions to current induced avalanche in silicon power semiconductors. 9 refs., 5 figs.

  3. Heavy-ion induced genetic changes and evolution processes

    NASA Technical Reports Server (NTRS)

    Yang, C. H.; Craise, L. M.; Durante, M.; Mei, M.

    1994-01-01

    On Moon and Mars, there will be more galactic cosmic rays and higher radiation doses than on Earth. Our experimental studies showed that heavy ion radiation can effectively cause mutation and chromosome aberrations and that high Linear Energy Transfer (LET) heavy-ion induced mutants can be irreversible. Chromosome translocations and deletions are common in cells irradiated by heavy particles, and ionizing radiations are effective in causing hyperploidy. The importance of the genetic changes in the evolution of life is an interesting question. Through evolution, there is an increase of DNA content in cells from lower forms of life to higher organisms. The DNA content, however, reached a plateau in vertebrates. By increasing DNA content, there can be an increase of information in the cell. For a given DNA content, the quality of information can be changed by rearranging the DNA. Because radiation can cause hyperploidy, an increase of DNA content in cells, and can induce DNA rearrangement, it is likely that the evolution of life on Mars will be effected by its radiation environment. A simple analysis shows that the radiation level on Mars may cause a mutation frequency comparable to that of the spontaneous mutation rate on Earth. To the extent that mutation plays a role in adaptation, radiation alone on Mars may thus provide sufficient mutation for the evolution of life.

  4. Heavy-ion induced genetic changes and evolution processes

    NASA Technical Reports Server (NTRS)

    Yang, C. H.; Craise, L. M.; Durante, M.; Mei, M.

    1994-01-01

    On Moon and Mars, there will be more galactic cosmic rays and higher radiation doses than on Earth. Our experimental studies showed that heavy ion radiation can effectively cause mutation and chromosome aberrations and that high Linear Energy Transfer (LET) heavy-ion induced mutants can be irreversible. Chromosome translocations and deletions are common in cells irradiated by heavy particles, and ionizing radiations are effective in causing hyperploidy. The importance of the genetic changes in the evolution of life is an interesting question. Through evolution, there is an increase of DNA content in cells from lower forms of life to higher organisms. The DNA content, however, reached a plateau in vertebrates. By increasing DNA content, there can be an increase of information in the cell. For a given DNA content, the quality of information can be changed by rearranging the DNA. Because radiation can cause hyperploidy, an increase of DNA content in cells, and can induce DNA rearrangement, it is likely that the evolution of life on Mars will be effected by its radiation environment. A simple analysis shows that the radiation level on Mars may cause a mutation frequency comparable to that of the spontaneous mutation rate on Earth. To the extent that mutation plays a role in adaptation, radiation alone on Mars may thus provide sufficient mutation for the evolution of life.

  5. A simple calculation method for heavy ion induced soft error rate in space environment

    NASA Astrophysics Data System (ADS)

    Galimov, A. M.; Elushov, I. V.; Zebrev, G. I.

    2016-12-01

    In this paper based on the new parameterization shape, an alternative heavy ion induced soft errors characterization approach is proposed and validated. The method provides an unambiguous calculation procedure to predict an upset rate in highly-scaled memory in a space environment.

  6. Repair and misrepair of heavy-ion-induced chromosomal damage

    NASA Astrophysics Data System (ADS)

    Goodwin, E.; Blakely, E.; Ivery, G.; Tobias, C.

    The premature chromosome condensation (PCC) technique was used to investigate chromosomal damage, repair, and misrepair in the G1 phase of a human/hamster hybrid cell line that contains a single human chromosome. Plateau-phase cell cultures were exposed to either x-rays or a 425 MeV/u beam of neon ions near the Bragg peak where the LET is 183 keV/μm. An in situ hybridization technique coupled to fluorescent staining of PCC spreads confirmed the linearity of the dose response for initial chromatin breakage in the human chromosome to high doses (1600 cGy x-ray or 1062 cGy Ne). On Giemsa-stained slides, initial chromatin breakage in the total genome and the rejoining kinetics of these breaks were determined. As a measure of chromosomal misrepair, ring PCC aberrations were also scored. Ne ions were about 1.5 x more effective per unit dose compared to x-rays at producing the initially measured chromatin breakage. 90% of the x-ray-induced breaks rejoined in cells incubated at 37°C after exposure. In contrast, only 50% of Ne-ion-induced breaks rejoined. In the irradiated G1 cells, ring PCC aberrations increased with time apparently by first order kinetics after either x-ray or Ne exposures. However, far fewer rings formed in Ne-irradiated cells after a dose giving a comparable initial number of chromatin breaks. Following x-ray exposures, the yield of rings formed after long repair times (6 to 9 hrs) fit a quadratic dose-response curve. These results indicate quantitative and qualitative differences in the chromosomal lesions induced by low- and high-LET radiations.

  7. Heavy ion induced changes in small intestinal parameters

    NASA Astrophysics Data System (ADS)

    Carr, K. E.; McCullough, J. S.; Brennan, P.; Hayes, T. L.; Ainsworth, E. J.; Nelson, A. C.

    1994-10-01

    The effects on 17 different structural parameters of mouse small intestine three days after treatment with three types of heavy ion (neon, iron and niobium) are compared, the first two being of particular relevance to space flight. The data for niobium are given in full, showing that changes after niobium ion treatment are not standard and are concentrated in the epithelial compartment, with few of the parameters having a response which is dose dependent. When comparisons are made for the three types of heavy ion, the damage is greatest after neon ion irradiation, implying that the additional non-epithelial damage produced as LET rises from X rays through neutrons to neon ions is not necessarily maintained as LET continues to rise. Further understanding is therefore needed of the balance between changes affecting the vascular and absorptive components of the organ. Variation from group to group is also important, as is variation of strain or gastrointestinal status. All such factors are important in the understanding of changes in multicellular organs after exposure to heavy ion radiation.

  8. Heavy ion induced double strand breaks in bacteria and bacteriophages

    NASA Astrophysics Data System (ADS)

    Micke, U.; Schäfer, M.; Anton, A.; Horneck, G.; Bücker, H.

    DNA damage induced by heavy ions in bacterial cells and bacteriophages such as Bacillus subtilis, E. coli and Bacteriophage Tl were investigated by analyzing the double strand breaks in the chromosomal DNA. This kind of lesion is considered as one of the main reasons for lethal events. To analyze double strand breaks in long molecules of DNA - up to some Mbp in length - the technique of pulse field agarose gel electrophoresis has been used. This allows the detection of one double strand break per genome. Cell lysis and DNA isolation were performed in small agarose blocks directly. This procedure secured minimum DNA destruction by shearing forces. After running a gel, the DNA was stained with ethidium bromide. The light intensity of ethidium bromide fluorescence for both the outcoming (running) DNA and the remaining intact DNA were measured by scanning. The mean number of double strand breaks was calculated by determining the quotient of these intensities. Strand break induction after heavy ion and X-ray irradiation was compared.

  9. Multimodal Fission in Heavy-Ion Induced Reactions

    SciTech Connect

    Pokrovskiy, I. V.; Bogachev, A. A.; Iitkis, M. G.; Iitkis, J. M.; Kondratiev, N. A.; Kozulin, E. M.; Dorvaux, O.; Rowley, N.; Schmitt, Ch.; Stuttge, L.

    2006-08-14

    Mass, energy and folding angle distributions of the fission fragments as well as multiplicities of neutron and gamma-quanta emissions accompanying the fission process were measured for fission of 226Th, 227Pa and 234Pu compound nuclei produced in reactions with 18O and 26Mg projectiles over a wide energy range. Data were analyzed with respect to the presence of fission modes. Asymmetric fission was observed even at very high initial excitation for all the measured systems. The so-called fission mode S1 (caused by the proton shell Z{approx}50 and neutron shell N{approx}82 in heavy fragment) was found to be dominant in asymmetric fission of 234Pu. Reactions with not full linear momentum transfer were observed in the folding spectra for all the measured systems.

  10. Molecular dynamics simulations of swift heavy ion induced defect recovery in SiC

    SciTech Connect

    Backman, Marie; Toulemonde, Marcel; Pakarinen, Olli H; Juslin, Niklas; Djurabekova, Flyura; Nordlund, Kai; Debelle, Aurelien; Weber, William J

    2013-01-01

    Swift heavy ions induce a high density of electronic excitations that can cause the formation of amorphous ion tracks in insulators. No ion tracks have been observed in the semiconductor SiC, but recent experimental work suggests that irradiation damaged SiC can undergo defect recovery under swift heavy ion irradiation. It is believed that local heating of the lattice due to the electronic energy deposition can anneal, and thereby recover, some of the disordered structure. We simulate the local heating due to the ions by the inelastic thermal spike model and perform molecular dynamics simulations of dierent model damage states to study the defect recovery on an atomistic level. We find significant recovery of point defects and a disordered layer, as well as recrystallization at the amorphous-to-crystalline interface of an amorphous layer. The simulation results support the swift heavy ion annealing hypothesis.Swift heavy ions induce a high density of electronic excitations that can cause the formation of amorphous ion tracks in insulators. No ion tracks have been observed in the semiconductor SiC, but recent experimental work suggests that irradiation damaged SiC can undergo defect recovery under swift heavy ion irradiation. It is believed that local heating of the lattice due to the electronic energy deposition can anneal, and thereby recover, some of the disordered structure. We simulate the local heating due to the ions by the inelastic thermal spike model and perform molecular dynamics simulations of dierent model damage states to study the defect recovery on an atomistic level. We find significant recovery of point defects and a disordered layer, as well as recrystallization at the amorphous-to-crystalline interface of an amorphous layer. The simulation results support the swift heavy ion annealing hypothesis.

  11. Heavy-Ion-Induced Degradation in SiC Schottky Diodes: Incident Angle and Energy Deposition Dependence

    NASA Astrophysics Data System (ADS)

    Javanainen, Arto; Turowski, Marek; Galloway, Kenneth F.; Nicklaw, Christopher; Ferlet-Cavrois, Véronique; Bosser, Alexandre; Lauenstein, Jean-Marie; Muschitiello, Michele; Pintacuda, Francesco; Reed, Robert A.; Schrimpf, Ronald D.; Weller, Robert A.; Virtanen, A.

    2017-08-01

    Heavy-ion-induced degradation in the reverse leakage current of SiC Schottky power diodes exhibits a strong dependence on the ion angle of incidence. This effect is studied experimentally for several different bias voltages applied during heavy-ion exposure. In addition, TCAD simulations are used to give insight on the physical mechanisms involved.

  12. Heavy ion induced mutations in mammalian cells: Cross sections and molecular analysis

    NASA Technical Reports Server (NTRS)

    Stoll, U.; Schmidt, P.; Schneider, E.; Kiefer, J.

    1994-01-01

    Our investigations of heavy ion-induced mutations in mammalian cells, which had been begun a few years ago, were systematically continued. For the first time, it was possible to cover a large LET range with a few kinds of ions. To do this, both UNILAC and SIS were used to yield comparable data for a large energy range. This is a necessary condition for a comprehensive description of the influence of such ion parameters as energy and LET. In these experiments, the induced resistance against the poison 6-thioguanin (6-TG), which is linked to the HPRT locus on the genome, is being used as mutation system. In addition to the mutation-induction cross-section measurements, the molecular changes of the DNA are being investigated by means of Multiplex PCR ('Polymerase Chain Reaction') gene amplification. From these experiments we expect further elucidation of the mutation-inducing mechanisms composing the biological action of heavy-ion radiation.

  13. Heavy ion induced DNA-DSB in yeast and mammalian cells

    NASA Technical Reports Server (NTRS)

    Loebrich, M.; Ikpeme, S.; Kiefer, J.

    1994-01-01

    Molecular changes at the DNA are assumed to be the main cause for radiation effects in a number of organisms. During the course of the last decades techniques have been developed for measuring DNA double-strand breaks (dsb), generally assumed to be the most critical DNA lesions. The outcome of all those different approaches portrays a collection of data useful for a theoretical description of radiation action mechanisms. However, in the case of heavy ion induced DNA dsb the picture is not quite clear yet and further projects and strategies have to be developed. The biological systems studied in our group are yeast and mammalian cells. While in the case of yeast cells technical and methodical reasons highlight these organisms mammalian cells reach greater importance when dsb repair studies are performed. In both types of organisms the technique of pulsed-field gel electrophoresis (PFGE) is applied, although with different modifications and evaluation procedures mainly due to the different genome sizes.

  14. Study on swift heavy ions induced modifications of Ag-ZnO nanocomposite thin film

    NASA Astrophysics Data System (ADS)

    Singh, S. K.; Singhal, R.; Siva Kumar, V. V.

    2017-03-01

    In the present work, swift heavy ion (SHI) irradiation induced modifications in structural and optical properties of Ag-ZnO nanocomposite thin films have been investigated. Ag-ZnO nanocomposite (NCs) thin films were synthesized by RF magnetron sputtering technique and irradiated with 100 MeV Ag7+ ions at three different fluences 3 × 1012, 1 × 1013 and 3 × 1013 ions/cm2. Rutherford Backscattering Spectrometry revealed Ag concentration to be ∼8.0 at.%, and measured thickness of the films was ∼55 nm. Structural properties of pristine and irradiated films have been analyzed by X-ray diffraction analysis and found that variation in crystallite size of the film with ion irradiation. X-ray photoelectron spectroscopy (XPS) indicates the formation of Ag-ZnO nanocomposite thin film with presence of Ag, Zn and O elements. Oxidation state of Ag and Zn also estimated by XPS analysis. Surface plasmon resonance (SPR) of Ag nanoparticle has appeared at ∼475 nm in the pristine thin film, which is blue shifted by ∼30 nm in film irradiated at fluence of 3 × 1012 ions/cm2 and completely disappeared in film irradiated at higher fluences, 1 × 1013 and 3 × 1013 ions/cm2. A marginal change in the optical band gap of Ag-ZnO nanocomposite thin film is also found with increasing ion fluence. Surface morphology of pristine and irradiated films have been studied using Atomic Force Microscopy (AFM). Raman and Photo-luminance (PL) spectra of nanocomposite thin films have been investigated to understand the ion induced modifications such as lattice defects and disordering in the nanocomposite thin film.

  15. Swift heavy ion induced optical and structural modifications in RF sputtered nanocrystalline ZnO thin film

    NASA Astrophysics Data System (ADS)

    Singh, S. K.; Singhal, R.; Vishnoi, R.; Kumar, V. V. S.; Kulariya, P. K.

    2017-01-01

    In the present study, 100 MeV Ag7+ ion beam-induced structural and optical modifications of nanocrystalline ZnO thin films are investigated. The nanocrystalline ZnO thin films are grown using radio frequency magnetron sputtering and irradiated at fluences of 3 × 1012, 1 × 1013 and 3 × 1013 ions/cm2. The incident swift heavy ions induced change in the crystallinity together with the preferential growth of crystallite size along the c axis (002) orientation. The average crystallite size is found to be increased from 10.8 ± 0.7 to 20.5 ± 0.3 nm with increasing the ion fluence. The Atomic force microscopy analysis confirms the variation in the surface roughness by varying the incident ion fluences. The UV-visible spectroscopy shows the decrement in transmittance of the film with ion irradiation. The micro-Raman spectra of ZnO thin films are investigated to observe ion-induced modifications which support the increased lattice defects with higher fluence. The variation in crystallinity indicates that ZnO-based devices can be used in piezoelectric transduction mechanism.

  16. Swift heavy ion induced optical and structural modifications in RF sputtered nanocrystalline ZnO thin film

    NASA Astrophysics Data System (ADS)

    Singh, S. K.; Singhal, R.; Vishnoi, R.; Kumar, V. V. S.; Kulariya, P. K.

    2017-05-01

    In the present study, 100 MeV Ag7+ ion beam-induced structural and optical modifications of nanocrystalline ZnO thin films are investigated. The nanocrystalline ZnO thin films are grown using radio frequency magnetron sputtering and irradiated at fluences of 3 × 1012, 1 × 1013 and 3 × 1013 ions/cm2. The incident swift heavy ions induced change in the crystallinity together with the preferential growth of crystallite size along the c axis (002) orientation. The average crystallite size is found to be increased from 10.8 ± 0.7 to 20.5 ± 0.3 nm with increasing the ion fluence. The Atomic force microscopy analysis confirms the variation in the surface roughness by varying the incident ion fluences. The UV-visible spectroscopy shows the decrement in transmittance of the film with ion irradiation. The micro-Raman spectra of ZnO thin films are investigated to observe ion-induced modifications which support the increased lattice defects with higher fluence. The variation in crystallinity indicates that ZnO-based devices can be used in piezoelectric transduction mechanism.

  17. Vitamin D-metabolites from human plasma and mass spectrometric analysis by fast heavy ion induced desorption

    NASA Astrophysics Data System (ADS)

    Fohlman, J.; Peterson, P. A.; Kamensky, I.; Håkansson, P.; Sundqvist, B.

    1982-07-01

    D-vitamin metabolites have been isolated from human serum employing chromatographic techniques. The serum carrier protein for vitamin D (DBP) was first isolated by immunosorbent chromatography. Lipid ligands associated with DBP were then extracted with hexane and separated by high pressure liquid chromatography (HPLC). Detection of vitamin D metabolites by their absorbance of ultraviolet light is not sufficiently sensitive to monitor all vitamin D derivatives from a few millilitres of serum. Therefore, further analyses are necessary to quantitate these compounds. We have begun to develop a mass spectrometric method to achieve a reliable, quantitative procedure. As a first step towards this goal a number of pure samples of vitamin D compounds have been studied in a time-of-flight mass spectrometer based on fast heavy ion induced desorption. All vitamin D compounds examined could be detected and identified by their molecular ion and fragment spectra.

  18. Method for studying a sample of material using a heavy ion induced mass spectrometer source

    DOEpatents

    Fries, D.P.; Browning, J.F.

    1999-02-16

    A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high n,f reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu. 3 figs.

  19. System for studying a sample of material using a heavy ion induced mass spectrometer source

    DOEpatents

    Fries, David P.; Browning, James F.

    1998-01-01

    A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high n,f reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu.

  20. System for studying a sample of material using a heavy ion induced mass spectrometer source

    DOEpatents

    Fries, D.P.; Browning, J.F.

    1998-07-21

    A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high (n,f) reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu. 3 figs.

  1. Method for studying a sample of material using a heavy ion induced mass spectrometer source

    DOEpatents

    Fries, David P.; Browning, James F.

    1999-01-01

    A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high n,f reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu.

  2. Resection is a major repair pathway of heavy ion-induced DNA lesions

    NASA Astrophysics Data System (ADS)

    Durante, Marco; Averbeck, Nicole; Taucher-Scholz, Gisela

    Space radiation include densely ionizing heavy ions, which can produce clustered DNA damage with high frequency in human cells. Repair of these complex lesions is generally assumed to be more difficult than for simple double-strand breaks. We show here that human cells use break resection with increasing frequency after exposure to heavy ions. Resection can lead to misrepair of the DNA lesion, via microhomology mediated end-joining. Resection can therefore be responsible for the increased effectiveness of heavy ions in the induction of mutations and genetic late effects.

  3. Heavy-ion-induced production and preseparation of short-livedisotopes for chemistry experiments

    SciTech Connect

    Dullmann, Christoph E.; Folden III, Charles M.; Gregorich, Kenneth E.; Hoffman, Darleane C.; Leitner, Daniela; Pang, Gregory K.; Sudowe, Ralf; Zielinski, Peter M.; Nitsche, Heino

    2005-02-24

    Physical separation of short-lived isotopes produced inheavy-ion-induced fusion reactions is a powerful and well know method andoften applied in investigations of the heaviest elements, called thetransactinides (Z>=104). By extracting these isotopes from a recoilseparator, they can be made available for transport to setups locatedoutside the heavily shielded irradiation position such as chemistrysetups. This physical preseparation technique overcomes many limitationscurrently faced in the chemical investigation of transactinides. Here wedescribe the basic principle using relatively short-lived isotopes of thelighter group 4 elements zirconium (Zr) and hafnium (Hf) that are used asanalogs of the lightest transactinide element, rutherfordium (Rf, element104). The Zr and Hf isotopes were produced at the LBNL 88-Inch Cyclotronusing a cocktail of 18O and 50Ti beams and the appropriate targets.Subsequently, the isotopes were physically separated in the BerkeleyGas-filled Separator (BGS) and guided to a Recoil Transfer Chamber (RTC)to transfer them to chemistry setups. The magnetic rigidities of thereaction products in low-pressure helium gas were measured and theiridentities determined with gamma-pectroscopy. Using preseparated isotopeshas the advantages of low background and beam plasma free environment forchemistry experiments. The new possibilities that open up for chemicalinvestigations of transactinide elements are descr ibed. The method canreadily be applied to homologous elements within other groups in theperiodic table.

  4. Swift heavy ion-induced amorphization of CaZrO3 perovskite

    NASA Astrophysics Data System (ADS)

    Lang, Maik; Zhang, Fuxiang; Li, Weixing; Severin, Daniel; Bender, Markus; Klaumünzer, Siegfried; Trautmann, Christina; Ewing, Rodney C.

    2012-09-01

    Perovskite, ABO3, structures are an important class of ceramics with a large variety of derivative structure-types (cubic, tetragonal, hexagonal, orthorhombic, and rhombohedral). Radiation damage in perovskites is of interest due to their potential as actinide waste forms and to understand radiation effects in uranium- and thorium-bearing phases. Powder CaZrO3 perovskite was irradiated with 940-MeV Au ions up to 1.5 × 1013 ions/cm2. Changes in the crystal structure were followed in situ as function of fluence by means of a sequence of X-ray diffraction (XRD) measurements. Ion-induced amorphization is evidenced by a decrease in diffraction intensity and an increase in diffuse scattering. Based on XRD measurements, as well as transmission electron microscopy (TEM), CaZrO3 is completely amorphized at a fluence of 1.5 × 1013 ions/cm2. From the evolution of the integrated XRD-maxima intensities with fluence, the diameter of the amorphous tracks is estimated to be 6.0 ± 0.6 nm, which is independently confirmed by bright-field TEM images: 6.7 ± 0.4 nm. Changes in the positions of diffraction maxima may be caused by at least two processes. Broadening of the diffraction maxima is analyzed using a Williamson-Hall plot. Strain-induced broadening is the dominant process.

  5. A new setup for the investigation of swift heavy ion induced particle emission and surface modifications

    SciTech Connect

    Meinerzhagen, F.; Breuer, L.; Bukowska, H.; Herder, M.; Schleberger, M.; Wucher, A.; Bender, M.; Severin, D.; Lebius, H.

    2016-01-15

    The irradiation with fast ions with kinetic energies of >10 MeV leads to the deposition of a high amount of energy along their trajectory (up to several ten keV/nm). The energy is mainly transferred to the electronic subsystem and induces different secondary processes of excitations, which result in significant material modifications. A new setup to study these ion induced effects on surfaces will be described in this paper. The setup combines a variable irradiation chamber with different techniques of surface characterizations like scanning probe microscopy, time-of-flight secondary ion, and neutral mass spectrometry, as well as low energy electron diffraction under ultra high vacuum conditions, and is mounted at a beamline of the universal linear accelerator (UNILAC) of the GSI facility in Darmstadt, Germany. Here, samples can be irradiated with high-energy ions with a total kinetic energy up to several GeVs under different angles of incidence. Our setup enables the preparation and in situ analysis of different types of sample systems ranging from metals to insulators. Time-of-flight secondary ion mass spectrometry enables us to study the chemical composition of the surface, while scanning probe microscopy allows a detailed view into the local electrical and morphological conditions of the sample surface down to atomic scales. With the new setup, particle emission during irradiation as well as persistent modifications of the surface after irradiation can thus be studied. We present first data obtained with the new setup, including a novel measuring protocol for time-of-flight mass spectrometry with the GSI UNILAC accelerator.

  6. Swift heavy ion induced single event upsets in high density UV-EPROM’s

    NASA Astrophysics Data System (ADS)

    Dahiwale, S. S.; Shinde, N. S.; Kanjilal, D.; Bhoraskar, V. N.; Dhole, S. D.

    2008-04-01

    A few high density UV-EPROM's (32Kb × 8) were irradiated with 5.41 MeV energy α-particles with fluences from 104 to 108 alphas/cm2 and 100 MeV nickel, iodine and silver ions for low fluences between 5 × 107 and 108 ions/cm2. The energy and ion species was selected on the basis of predicted threshold values of linear energy transfer (LET) in silicon. The program which was stored in the memory found to be changed from 0 to 1 and 1 to 0 state, respectively. On the basis of changed states, the cross-sections (σ) were calculated to investigate the single event effects/upsets. No upset was observed in case of α-particle since it has very low LET, but the SEU cross-section found to be more in case of Iodine i.e. 2.29 × 10-3 cm2 than that of nickel, 2.12 × 10-3 cm2 and silver, 2.26 × 10-3. This mainly attributes that LET for iodine is more as compared to silver and nickel ions, which deposits large amount of energy near the sensitive node of memory cell in the form of electron-hole pairs required to change the state. These measured SEU cross-section were also compared with theoretically predicted values along with the Weibull distribution fit to the ion induced experimental SEU data. The theoretical predicted SEU cross-section 3.27 × 10-3 cm2 found to be in good agreement with the measured SEU cross-section.

  7. A new setup for the investigation of swift heavy ion induced particle emission and surface modifications

    NASA Astrophysics Data System (ADS)

    Meinerzhagen, F.; Breuer, L.; Bukowska, H.; Bender, M.; Severin, D.; Herder, M.; Lebius, H.; Schleberger, M.; Wucher, A.

    2016-01-01

    The irradiation with fast ions with kinetic energies of >10 MeV leads to the deposition of a high amount of energy along their trajectory (up to several ten keV/nm). The energy is mainly transferred to the electronic subsystem and induces different secondary processes of excitations, which result in significant material modifications. A new setup to study these ion induced effects on surfaces will be described in this paper. The setup combines a variable irradiation chamber with different techniques of surface characterizations like scanning probe microscopy, time-of-flight secondary ion, and neutral mass spectrometry, as well as low energy electron diffraction under ultra high vacuum conditions, and is mounted at a beamline of the universal linear accelerator (UNILAC) of the GSI facility in Darmstadt, Germany. Here, samples can be irradiated with high-energy ions with a total kinetic energy up to several GeVs under different angles of incidence. Our setup enables the preparation and in situ analysis of different types of sample systems ranging from metals to insulators. Time-of-flight secondary ion mass spectrometry enables us to study the chemical composition of the surface, while scanning probe microscopy allows a detailed view into the local electrical and morphological conditions of the sample surface down to atomic scales. With the new setup, particle emission during irradiation as well as persistent modifications of the surface after irradiation can thus be studied. We present first data obtained with the new setup, including a novel measuring protocol for time-of-flight mass spectrometry with the GSI UNILAC accelerator.

  8. Heavy-ion-induced sucrose radicals investigated using EPR and UV spectroscopy.

    PubMed

    Nakagawa, Kouichi; Karakirova, Yordanka; Yordanov, Nicola D

    2015-05-01

    The potential use of a sucrose dosimeter for estimating both linear energy transfer (LET) and the absorbed dose of heavy ion and X-ray radiation was investigated. The stable free radicals were produced when sucrose was irradiated with heavy ions, such as helium, carbon, silicon and neon ions, and when the X-ray radiation was similar to the obtained electron paramagnetic resonance (EPR) spectra, which were ∼7 mT wide and composed of several hyperfine structures. In addition, the total spin concentration resulting from heavy-ion irradiation increased linearly as the absorbed dose increased, and decreased logarithmically as the LET increased. These empirical relations imply that the LET at a certain dose can be determined from the spin concentration. For sucrose and alanine, both cross-sections following C-ion irradiation with a 50 Gy dose were ∼1.3 × 10(-12) [μm(2)], taking into account the molecular size of the samples. The values of these cross-sections imply that multiple ionizing particles were involved in the production of stable radicals. Furthermore, UV absorbance at 267 nm of an aqueous solution of irradiated sucrose was found to linearly increase with increasing absorbed dose. Therefore, the EPR and UV results suggest that sucrose can be a useful dosimeter for heavy-ion irradiation. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  9. Heavy-ion-induced sucrose radicals investigated using EPR and UV spectroscopy

    PubMed Central

    Nakagawa, Kouichi; Karakirova, Yordanka; Yordanov, Nicola D.

    2015-01-01

    The potential use of a sucrose dosimeter for estimating both linear energy transfer (LET) and the absorbed dose of heavy ion and X-ray radiation was investigated. The stable free radicals were produced when sucrose was irradiated with heavy ions, such as helium, carbon, silicon and neon ions, and when the X-ray radiation was similar to the obtained electron paramagnetic resonance (EPR) spectra, which were ∼7 mT wide and composed of several hyperfine structures. In addition, the total spin concentration resulting from heavy-ion irradiation increased linearly as the absorbed dose increased, and decreased logarithmically as the LET increased. These empirical relations imply that the LET at a certain dose can be determined from the spin concentration. For sucrose and alanine, both cross-sections following C-ion irradiation with a 50 Gy dose were ∼1.3 × 10−12 [μm2], taking into account the molecular size of the samples. The values of these cross-sections imply that multiple ionizing particles were involved in the production of stable radicals. Furthermore, UV absorbance at 267 nm of an aqueous solution of irradiated sucrose was found to linearly increase with increasing absorbed dose. Therefore, the EPR and UV results suggest that sucrose can be a useful dosimeter for heavy-ion irradiation. PMID:25480828

  10. Heavy-ion induced single-event upset in integrated circuits

    NASA Technical Reports Server (NTRS)

    Zoutendyk, J. A.

    1991-01-01

    The cosmic ray environment in space can affect the operation of Integrated Circuit (IC) devices via the phenomenon of Single Event Upset (SEU). In particular, heavy ions passing through an IC can induce sufficient integrated current (charge) to alter the state of a bistable circuit, for example a memory cell. The SEU effect is studied in great detail in both static and dynamic memory devices, as well as microprocessors fabricated from bipolar, Complementary Metal Oxide Semiconductor (CMOS) and N channel Metal Oxide Semiconductor (NMOS) technologies. Each device/process reflects its individual characteristics (minimum scale geometry/process parameters) via a unique response to the direct ionization of electron hole pairs by heavy ion tracks. A summary of these analytical and experimental SEU investigations is presented.

  11. Heavy-ion induced single-event upset in integrated circuits

    NASA Technical Reports Server (NTRS)

    Zoutendyk, J. A.

    1991-01-01

    The cosmic ray environment in space can affect the operation of Integrated Circuit (IC) devices via the phenomenon of Single Event Upset (SEU). In particular, heavy ions passing through an IC can induce sufficient integrated current (charge) to alter the state of a bistable circuit, for example a memory cell. The SEU effect is studied in great detail in both static and dynamic memory devices, as well as microprocessors fabricated from bipolar, Complementary Metal Oxide Semiconductor (CMOS) and N channel Metal Oxide Semiconductor (NMOS) technologies. Each device/process reflects its individual characteristics (minimum scale geometry/process parameters) via a unique response to the direct ionization of electron hole pairs by heavy ion tracks. A summary of these analytical and experimental SEU investigations is presented.

  12. Characterization of a heavy-ion induced white flower mutant of allotetraploid Nicotiana tabacum.

    PubMed

    Kazama, Yusuke; Fujiwara, Makoto T; Takehisa, Hinako; Ohbu, Sumie; Saito, Hiroyuki; Ichida, Hiroyuki; Hayashi, Yoriko; Abe, Tomoko

    2013-01-01

    KEY MESSAGE : We characterized a white flower mutant of allotetraploid N. tabacum as a DFR-deficient mutant; one copy of DFR has a cultivar-specific frameshift, while the other was deleted by heavy-ion irradiation. In most plants, white-flowered mutants have some kind of deficiency or defect in their anthocyanin biosynthetic pathway. Nicotiana tabacum normally has pink petals, in which cyanidin is the main colored anthocyanidin. When a relevant gene in the cyanidin biosynthetic pathway is mutated, the petals show a white color. Previously, we generated white-flowered mutants of N. tabacum by heavy-ion irradiation, which is accepted as an effective mutagen. In this study, we determined which gene was responsible for the white-flowered phenotype of one of these mutants, cv. Xanthi white flower 1 (xwf1). Southern blot analysis using a DNA fragment of the dihydroflavonol 4-reductase (DFR) gene as a probe showed that the xwf1 mutant lacked signals that were present in wild-type genomic DNAs. Sequence analysis demonstrated that one copy of the DFR gene (NtDFR2) was absent from the genome of the xwf1 mutant. The other copy of the DFR gene (NtDFR1) contained a single-base deletion resulting in a frameshift mutation, which is a spontaneous mutation in cv. Xanthi. Introduction of NtDFR2 cDNA into the petal limbs of xwf1 by particle bombardment resulted in production of the pink-colored cells, whereas introduction of NtDFR1 cDNA did not. These results indicate that xwf1 is a DFR-deficient mutant. One copy of NtDFR1 harbors a spontaneous frameshift mutation, while the other copy of NtDFR2 was deleted by heavy-ion beam irradiation.

  13. Swift heavy ion induced changes in magnetization of cobalt thin films

    SciTech Connect

    Attri, Asha Nair, Lekha

    2016-05-06

    The effects of 45 MeV Li{sup 3+} ions and 100 MeV O{sup 7+} ions irradiation on magnetic properties of nanoparticles of 25 nm Cobalt thin films, synthesized by e-beam sputtering have been studied. Significant changes in the hysteresis loop are observed with different irradiating fluence, which may be attributed to formation of cluster of defects in the nano-crystalline samples due to swift heavy ion (SHI) irradiation along with the distortion in the lattice parameter.

  14. Swift heavy ion induced nano-dimensional phase separation in liquid immiscible binary Mn-Bi

    NASA Astrophysics Data System (ADS)

    Srivastava, S. K.; Khan, S. A.; Sudheer Babu, P.; Avasthi, D. K.

    2014-08-01

    Pulsed laser deposited 60 nm thin film of homogeneous Mn0.82Bi0.18 composite has been irradiated by 100 MeV Au ions at fluence 1 × 1013 ions/cm2, and investigated by field emission scanning electron microscopy, X-ray diffraction, magnetic hysteresis, X-ray photoelectron spectroscopy, and nanoindentation measurements. Dispersed nanostructures of soft Bi-rich phase of about 20 nm diameter emerged in a hard Mn-rich matrix on irradiation. Such structures, as synthesized by the present novel swift heavy ion irradiation approach, are usable as self-lubricating thin films.

  15. Heavy ion-induced amorphlsation of Zr(Fe, Cr) 2 precipitates in Zircaloy-4

    NASA Astrophysics Data System (ADS)

    Lefebvre, Florence; Lemaignan, Clément

    1989-05-01

    It is generally accepted that the impact of neutron irradiation on Zircaloy microstructure may be involved on the behaviour of PWR fuel cladding at high burnup during transients. In order to describe and understand the microstructure evolution in reactor, neutron damage has been simulated with heavy ions on a Zircaloy-4 recrystallized sheet up to 100 dpa at 873 K. A complete amorphisation is observed for all precipitates, and a chromium and iron segregation ring is measured around them. The contributions of nuclear collisions and thermal diffusion as driving forces of both phenomena are discussed, as well as the impact of it on Pellet Cladding Interaction (PCI) behaviour.

  16. [Reaction mechanism studies of heavy ion induced nuclear reactions]. Annual progress report, [January 1992--February 1993

    SciTech Connect

    Mignerey, A.C.

    1993-02-01

    Completed work is summarized on the topics of excitation energy division in deep-inelastic reactions and the onset of multifragmentation in La-induced reactions at E/A = 45 MeV. Magnetic fields are being calculated for the PHOBOS detector system, a two-arm multiparticle spectrometer for studying low-transverse-momentum particles produced at the Relativistic Heavy Ion Collider. The Maryland Forward Array is being developed for detection of the reaction products from very peripheral collisions; it consists of two individual units of detectors: the annular silicon detector in front and the plastic phoswich detector at back.

  17. Swift heavy ion induced modifications in optical and electrical properties of cadmium selenide thin films

    NASA Astrophysics Data System (ADS)

    Choudhary, Ritika; Chauhan, Rishi Pal

    2017-07-01

    The modification in various properties of thin films using high energetic ion beam is an exciting area of basic and applied research in semiconductors. In the present investigations, cadmium selenide (CdSe) thin films were deposited on ITO substrate using electrodeposition technique. To study the swift heavy ion (SHI) induced effects, the deposited thin films were irradiated with 120 MeV heavy Ag9+ ions using pelletron accelerator facility at IUAC, New Delhi, India. Structural phase transformation in CdSe thin film from metastable cubic phase to stable hexagonal phase was observed after irradiation leading to decrease in the band gap from 2.47 eV to 2.12 eV. The phase transformation was analyzed through X-ray diffraction patterns. During SHI irradiation, Generation of high temperature and pressure by thermal spike along the trajectory of incident ions in the thin films might be responsible for modification in the properties of thin films.[Figure not available: see fulltext.

  18. Single ion induced surface nanostructures: a comparison between slow highly charged and swift heavy ions.

    PubMed

    Aumayr, Friedrich; Facsko, Stefan; El-Said, Ayman S; Trautmann, Christina; Schleberger, Marika

    2011-10-05

    This topical review focuses on recent advances in the understanding of the formation of surface nanostructures, an intriguing phenomenon in ion-surface interaction due to the impact of individual ions. In many solid targets, swift heavy ions produce narrow cylindrical tracks accompanied by the formation of a surface nanostructure. More recently, a similar nanometric surface effect has been revealed for the impact of individual, very slow but highly charged ions. While swift ions transfer their large kinetic energy to the target via ionization and electronic excitation processes (electronic stopping), slow highly charged ions produce surface structures due to potential energy deposited at the top surface layers. Despite the differences in primary excitation, the similarity between the nanostructures is striking and strongly points to a common mechanism related to the energy transfer from the electronic to the lattice system of the target. A comparison of surface structures induced by swift heavy ions and slow highly charged ions provides a valuable insight to better understand the formation mechanisms.

  19. Population of collective bands in Dy isotopes using heavy ion induced transfer reactions

    SciTech Connect

    Cresswell, A.J.; Butler, P.A.; Cline, D.; Cunningham, R.A.; Devlin, M.; Hannachi, F.; Ibbotson, R.; Jones, G.D.; Jones, P.M.; Simon, M.; Simpson, J.; Smith, J.F.; Wu, C.Y. ||

    1995-10-01

    It is demonstrated that low-lying collective bands in deformed nuclei are strongly populated by quasielastic heavy ion transfer reactions at near barrier energies. The {sup 161}Dy({sup 61}Ni,{sup 62}Ni){sup 160}Dy and {sup 161}Dy({sup 61}Ni,{sup 60}Ni){sup 162}Dy reactions at a beam energy of 270 MeV have been studied using a particle-{gamma} technique. Significant population of sidebands in {sup 160}Dy was observed, particularly the {ital S} band built upon the [{nu}({ital i}{sub 13/2})]{sup 2} configuration and the {ital K}{sup {pi}}=1{sup {minus}}, 2{sup {minus}}, and {gamma} bands. For {sup 162}Dy the only sideband significantly populated was the {gamma} band.

  20. Time delays in heavy-ion-induced fission of medium-Z nuclei, measured by crystal blocking

    SciTech Connect

    Andersen, J. U.; Chevallier, J.; Forster, J. S.; Karamian, S. A.; Vane, C Randy; Beene, James R; Gross, Carl J; Krause, Herbert F; Liang, J Felix; Shapira, Dan; Uguzzoni, A.

    2012-01-01

    Time delays in fission induced by bombardment of Mo with 170- and 180-MeV {sup 32}S, 225- and 240-MeV {sup 48}Ti, and 300-MeV {sup 58}Ni have been measured by observation of crystal blocking of fission fragments. In contrast to earlier measurements with a W target, the results are consistent with fission of a compound nucleus in competition with mainly neutron emission. Most of the fissions happen on a time scale much shorter than attoseconds but there is a significant component of fission with much longer lifetimes. The measurements are reproduced with a standard statistical model, including a Kramers correction to fission widths from the viscosity of hot nuclear matter. These new results support the interpretation of our earlier measurements with a W target, which indicate that there is a transition in heavy-ion-induced fission at large atomic number and mass, from multichance fission in the standard Bohr-Wheeler picture to fission without formation of a compound nucleus. The process is slowed down by nuclear viscosity, with measured delays of order attoseconds.

  1. In situ study of heavy ion induced radiation damage in NF616 (P92) alloy

    NASA Astrophysics Data System (ADS)

    Topbasi, Cem; Motta, Arthur T.; Kirk, Mark A.

    2012-06-01

    NF616 is a nominal 9Cr ferritic-martensitic steel that is amongst the primary candidates for cladding and duct applications in the Sodium-Cooled Fast Reactor, one of the Generation IV nuclear energy systems. In this study, an in situ investigation of the microstructure evolution in NF616 under heavy ion irradiation has been conducted. NF616 was irradiated to 8.4 dpa at 50 K and to 7.6 dpa at 473 K with 1 MeV Kr ions. Nano-sized defects first appeared as white dots in dark-field TEM images and their areal density increased until saturation (˜6 dpa). Dynamic observations at 50 K and 473 K showed appearance and disappearance of TEM-visible defect clusters under irradiation that continued above saturation dose. Quantitative analysis showed no significant change in the average size (˜3-4 nm) and distribution of defect clusters with increasing dose at 50 K and 473 K. These results indicate a cascade-driven process of microstructure evolution under irradiation in these alloys that involves both the formation of TEM-visible defect clusters by various degrees of cascade overlap and cascade induced defect cluster elimination. According to this mechanism, saturation of defect cluster density is reached when the rate of defect cluster formation by overlap is equal to the rate of cluster elimination during irradiation.

  2. Mechanism of the swift heavy ion induced epitaxial recrystallization in predamaged silicon carbide

    SciTech Connect

    Benyagoub, A.; Audren, A.

    2009-10-15

    Although silicon carbide has attracted extensive investigations of ion irradiation effects at low energy owing to its potential use in harsh environments, very few works were carried out in the field of ion irradiation at high energy. A recent preliminary study exploring the combination of low and high energy ion irradiation effects in silicon carbide revealed that the damaged layer formed by low energy ion irradiation can undergo an epitaxial recrystallization under subsequent swift heavy ion irradiation. The present paper is devoted to the investigation of the mechanisms at the origin of this phenomenon by performing additional experiments. A detailed analysis of the kinetics of this recrystallization effect demonstrates that the latter cannot be explained by the models proposed for the well-known ion-beam-induced epitaxial crystallization process. Furthermore, it is found that this effect can be accounted for by a mechanism combining the melting within the ion tracks of the amorphous zones through a thermal spike process and their subsequent epitaxial recrystallization initiated from the neighboring crystalline regions wherever the size of the latter surpasses a certain critical value.

  3. Swift heavy ion induced dewetting of metal oxide thin films on silicon

    NASA Astrophysics Data System (ADS)

    Bolse, T.; Paulus, H.; Bolse, W.

    2006-04-01

    We have observed that thin oxide coatings (NiO, Fe2O3) tend to dewet their Si substrate when being bombarded with swift heavy ions (350-600 MeV Au ions) even though the irradiation was carried out about 80 K and hence, the films never reached their melting point. Scanning electron and atomic force microscopy reveal a surprising similarity of the dewetting morphologies with those observed for molten polymer films on Si, which have recently been reported by others [S. Herminghaus, K. Jakobs, K. Mecke, J. Bischof, A. Fery, M. Ibn-Elhaj, S. Schlagowsky, Science 282 (1998) 916; R. Seemann, S. Herminghaus, K. Jacobs, J. Phys.: Condens. Matter 13 (2001) 4925]. Like in that cases also here heterogeneous and homogeneous hole nucleation could be identified. Heterogeneous nucleation is less pronounced in Fe2O3/Si than in NiO/Si. The occurrence of spinodal-like dewetting cannot be detected unambiguously. The dewetting kinetics were determined by means of Rutherford backscattering spectroscopy and found to slightly differ for the two compounds. The dewetting kinetics as well as the final dewetting pattern strongly depend on the initial film thicknesses. No dewetting occurs for film thicknesses above about 150 nm, while for very small thicknesses below about 40 nm the film decays into nm-sized spherical droplets. At intermediate film thicknesses percolated networks of small oxide bridges are formed.

  4. Nanoclay and swift heavy ions induced piezoelectric and conducting nanochannel based polymeric membrane for fuel cell

    NASA Astrophysics Data System (ADS)

    Jana, Karun Kumar; Srivastava, Anshuman; Parkash, Om; Avasthi, Devesh K.; Rana, Dipak; Shahi, Vinod K.; Maiti, Pralay

    2016-01-01

    Through nanochannels are fabricated in poly(vinylidene fluoride-co-hexafluoro propylene) films by bombarding swift heavy ions (SHI) of energy 80 MeV and thereby creating latent tracks in the ion passage followed by chemical etching of the amorphous track. The dimension of the nanochannel is varied from 34 to 65 nm using different fluences and by dispersing organically modified nanoclay in polymer matrix. The nanochannels are grafted with polystyrene using the free radicals caused by SHI irradiation followed by their sulfonation. Nanoclay nucleates piezoelectric β-phase in copolymer whose extent gets enhanced after irradiation, grafting and sulfonation leading to a better material. The efficiency of functionalized nanochannel conduction is studied through dc conductivity of the bulk film in the semiconducting range against the insulating nature of the pristine copolymer. Current-voltage (I-V) characteristic of the membrane exhibits strong fluence dependency and shows superior conduction in functionalized nanohybrid. Proton conductivity of the functionalized nanohybrid is 6.2 × 10-2 S cm-1, while methanol permeability drastically reduces indicating higher values of the selective parameter of the developed membrane as compared to Nafion. Membrane electrode assembly studies of functionalized nanohybrid show 0.63 V as open circuit voltage leading to power density of 30.8 mW/cm2, considerably higher than the functionalized copolymer.

  5. Swift heavy ion-induced recrysallization of silicon-on-insulator (SOI) structures

    NASA Astrophysics Data System (ADS)

    Virdi, G. S.; Pathak, B. C.; Avasthi, D. K.; Kanjilal, D.

    2002-02-01

    Buried Si 3N 4-Si interfaces and overlayer in silicon-on-insulator (SOI) structures were improved by irradiation with 100 MeV 107Ag after the synthesis of buried silicon nitride layers by high dose nitrogen ion-implantation. Auger electron spectroscopy (AES) depth profile analysis illustrates that the MeV heavy ions irradiation in the SOI structure, modifies the distribution of nitrogen that results in better stoichiometry of the buried silicon nitride layers and abrupt Si 3N 4-Si interfaces. Electron spin resonance (ESR) technique shows the improvement in the crystalline structure of the Si over layer. Current-voltage and high frequency capacitance-voltage ( C- V) characteristics were studied, and electrical breakdown measurements were performed on metal nitride silicon (MNS) structures fabricated after removing the Si over layer in the SOI structure. In the ion-beam irradiated SOI specimens, buried silicon nitride layer show a high breakdown field strength of 4.5-6.5 MV/cm as compared to that of 3.0-3.9 MV/cm in the unirradiated one. The C- V analysis of the MNS capacitors reveals that the buried Si 3N 4-Si substrate interface exhibits a better quality with reduced fixed insulator charge and interface state densities after the ion-beam irradiation. Mid-gap interface state density at the buried Si 3N 4-Si substrate interface was as low as 1.0×10 11 cm-2 V-2 after the ion-beam irradiation, which is comparable to that of silicon nitride films deposited on silicon (Si) by the conventional low pressure chemical vapor deposition technique. The role of MeV ion-beam irradiation in improving the properties of SOI structures has been discussed on the basis of various models.

  6. Swift heavy ion induced modification in morphological and physico-chemical properties of tin oxide nanocomposites

    NASA Astrophysics Data System (ADS)

    Jaiswal, Manoj Kumar; Kanjilal, D.; Kumar, Rajesh

    2013-11-01

    Nanocomposite thin films of tin oxide (SnO2)/titanium oxide (TiO2) were grown on silicon (1 0 0) substrates by electron beam evaporation deposition technique using sintered nanocomposite pellet of SnO2/TiO2 in the percentage ratio of 95:5. Sintering of the nanocomposite pellet was done at 1300 °C for 24 h. The thicknesses of these films were measured to be 100 nm during deposition using piezo-sensor attached to the deposition chamber. TiO2 doped SnO2 nanocomposite films were irradiated by 100 MeV Au8+ ion beam at fluence range varying from 1 × 1011 ions/cm2 to 5 × 1013 ions/cm2 at Inter University Accelerator Center (IUAC), New Delhi, India. Chemical properties of pristine and ion irradiation modified thin films were characterized by Fourier Transform Infrared (FTIR) spectroscopy. FTIR peak at 610 cm-1 confirms the presence of O-Sn-O bridge of tin (IV) oxide signifying the composite nature of pristine and irradiated thin films. Atomic Force Microscope (AFM) in tapping mode was used to study the surface morphology and grain growth due to swift heavy ion irradiation at different fluencies. Grain size calculations obtained from sectional analysis of AFM images were compared with results obtained from Glancing Angle X-ray Diffraction (GAXRD) measurements using Scherrer’s formulae. Phase transformation due to irradiation was observed from Glancing Angle X-ray Diffraction (GAXRD) results. The prominent 2θ peaks observed in GAXRD spectrum are at 30.67°, 32.08°, 43.91°, 44.91° and 52.35° in the irradiated films.

  7. Dynamical simulation of energy dissipation in asymmetric heavy-ion induced fission of {sup 200}Pb, {sup 213}Fr, and {sup 251}Es

    SciTech Connect

    Mirfathi, S. M.; Pahlavani, M. R.

    2008-12-15

    The dynamical model based on the asymmetric mass division has been applied to calculate pre-scission neutron multiplicity from heavy-ion induced fusion-fission reactions. Links between the pre-scission neutron multiplicity, excitation energy, and asymmetric mass distribution are clarified based on the Monte Carlo simulation and Langevin dynamics. The pre-scission neutron multiplicity is calculated and compared with the respective experimental data over a wide range of excitation energy and nonconstant viscosity. The analysis indicates a different effect for the application of asymmetric mass division in different energy regions of such processes.

  8. Compact Modeling and Simulation of Heavy Ion-Induced Soft Error Rate in Space Environment: Principles and Validation

    NASA Astrophysics Data System (ADS)

    Zebrev, Gennady I.; Galimov, Artur M.

    2017-08-01

    A simple physical model for calculation of the ion-induced soft error rate in space environment has been proposed, based on the phenomenological cross-sectional notion. The proposed numerical procedure is adapted to the multiple cell upset characterization in highly scaled memories. Nonlocality of the ion impact has been revealed as the key concept determining the difference between physical processes in low-scaled and highly scaled memories. The model has been validated by comparison between the simulation results and the literature on-board data. It was shown that the proposed method provides single-valued prediction results correlating well with on-board data-based solely on cross-sectional data and LET spectra without any hidden fitting parameters and procedures.

  9. Investigations on heavy ion induced Single-Event Transients (SETs) in highly-scaled FinFETs

    NASA Astrophysics Data System (ADS)

    Gaillardin, M.; Raine, M.; Paillet, P.; Adell, P. C.; Girard, S.; Duhamel, O.; Andrieu, F.; Barraud, S.; Faynot, O.

    2015-12-01

    We investigate Single-Event Transients (SET) in different designs of multiple-gate devices made of FinFETs with various geometries. Heavy ion experimental results are explained by using a thorough charge collection analysis of fast transients measured on dedicated test structures. Multi-level simulations are performed to get new insights into the charge collection mechanisms in multiple-gate devices. Implications for multiple-gate device design hardening are finally discussed.

  10. Fusion hindrance and quasi-fission in heavy-ion induced reactions: disentangling the effect of different parameters

    SciTech Connect

    Fioretto, E.; Stefanini, A. M.; Behera, B. R.; Corradi, L.; Gadea, A.; Latina, A.; Trotta, M.; Beghini, S.; Montagnoli, G.; Scarlassara, F.; Chizhov, A. Yu.; Itkis, I. M.; Itkis, M. G.; Kniajeva, G. N.; Kondratiev, N. A.; Kozulin, E. M.; Pokrovsky, I. V.; Sagaidak, R. N.; Voskressensky, V. M.; Courtin, S.

    2006-04-26

    Experimental results on the fusion inhibition effect near the Coulomb barrier due to the onset of the quasi-fission mechanism are presented. The investigation was focused on reactions induced by 48Ca projectiles on different heavy targets and comparing them to reactions induced by light ions such as 12C and 16O leading to the same compound nuclei. Cross sections and angular distributions of evaporation residues and fission fragments have been measured.

  11. [Reaction mechanism studies of heavy ion induced nuclear reactions]. [Dept. of Chemistry and Biochemistry, Univ. of Maryland, College Park, Maryland

    SciTech Connect

    Mignerey, A.C.

    1993-02-01

    Completed work is summarized on the topics of excitation energy division in deep-inelastic reactions and the onset of multifragmentation in La-induced reactions at E/A = 45 MeV. Magnetic fields are being calculated for the PHOBOS detector system, a two-arm multiparticle spectrometer for studying low-transverse-momentum particles produced at the Relativistic Heavy Ion Collider. The Maryland Forward Array is being developed for detection of the reaction products from very peripheral collisions; it consists of two individual units of detectors: the annular silicon detector in front and the plastic phoswich detector at back.

  12. 100 MeV Ni+7 swift heavy ion induced magnetism in cobalt doped ZnO thin films

    NASA Astrophysics Data System (ADS)

    Kumar, Sunil; Kumar, Ravi; Singh, D. P.

    2014-04-01

    Zn0.90Co0.10O thin films were prepared using Sol-Gel spin coating method. Films were irradiated with 100 MeV Ni+7 Swift Heavy Ions (SHI) with fluences 1× 1013 ions/cm2 using 15 UD tandem accelerator at IUAC New Delhi and its effect were studied on the structural, optical and magnetic properties of irradiated thin films. X-ray diffraction studies show single phase films with preferred c-axis orientation after irradiation. Ultraviolet-visible absorption spectroscopy shows red shift in the band gap of irradiated thin films. Magnetic field dependence of magnetization reveals weak ferromagnetism in irradiated thin films. AFM studies shows significant increase in the grain size and the surface roughness of the films after irradiation.

  13. Swift heavy ion induced structural and luminescence characterization of Y₂O₃:Eu³⁺ phosphor: a comparative study.

    PubMed

    Som, S; Sharma, S K; Lochab, S P

    2014-08-01

    We report a comparative study on structural and thermoluminescence modifications of Y2O3:Eu(3+) phosphor induced by 150 MeV Ni(7+), 120 MeV Ag(9+) and 110 MeV Au(8+) swift heavy ions (SHI) in the fluence range 1 × 10(11) to 1 × 10(13) ions/cm(2). X-Ray diffraction and transition electron microscopy studies confirm the loss of crystallinity of the phosphors after ion irradiation, which is greater in the case of Au ion irradiation. Structural refinement using the Rietveld method yields the various structural parameters of ion-irradiated phosphors. Thermoluminescence glow curves of ion-irradiated phosphors show a small shift in the position of the peaks, along with an increase in intensity with ion fluence. Stopping range of ions in Matter (SRIM) calculations were performed to correlate the change in thermoluminescence properties of various ion-irradiated phosphors. It shows that the defects created by 110 MeV Au(8+) ions are greater in number. Trapping parameters of ion-irradiated phosphors were calculated from thermoluminescence data using various glow curve analysis methods. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Simulation of energy and fluence dependence of heavy ion induced displacement damage factor in bipolar junction transistor

    NASA Astrophysics Data System (ADS)

    Kulkarni, S. R.; Ravindra, M.; Joshi, G. R.; Damle, R.

    2004-05-01

    This article presents the theoretical calculation of the variation of displacement damage factors as a function of energy and rad equivalent fluence in bipolar junction transistor for various particulate radiation viz ., He, Si, Cl, Ti, Ni, Br, Ag, I, and Au. The calculation is based on the experimental data on gamma-ray induced gain degradation in a commercial space borne BJT (2N3019). The method involves the calculation of gamma-ray dose (rad(Si)) equivalent of effective particle fluence. The linear energy transfer (LET) in silicon for different particle radiation obtained from TRIM calculation has been used for the conversion of gamma-dose into fluence of various particles. The estimation predicts a smooth increase in the displacement damage factor as the mass of the ion increases. Further, the displacement damage factor reaches a maximum at the same value of energy, which corresponds to maximum LET for all heavy ions. The maximum value of damage factor marginally decreases with increasing ion fluence for an ion of given energy. The results are compared with the data available in the literature for proton, deuteron, and helium induced displacement damage.

  15. Dissipation of the tilting degree of freedom in heavy-ion-induced fission from four-dimensional Langevin dynamics

    NASA Astrophysics Data System (ADS)

    Nadtochy, P. N.; Ryabov, E. G.; Cheredov, A. V.; Adeev, G. D.

    2016-10-01

    A stochastic approach based on four-dimensional Langevin fission dynamics is applied to the calculation of a wide set of experimental observables of excited compound nuclei from 199Pb to 248Cf formed in reactions induced by heavy ions. In the model under investigation, the tilting degree of freedom ( K coordinate) representing the projection of the total angular momentum onto the symmetry axis of the nucleus is taken into account in addition to three collective shape coordinates introduced on the basis of {c,h,α} parametrization. The evolution of the K coordinate is described by means of the Langevin equation in the overdamped regime. The friction tensor for the shape collective coordinates is calculated under the assumption of the modified version of the one-body dissipation mechanism, where the reduction coefficient ks of the contribution from the "wall" formula is introduced. The calculations are performed both for the constant values of the coefficient ks and for the coordinate-dependent reduction coefficient ks(q) which is found on the basis of the "chaos-weighted wall formula". Different possibilities of the deformation-dependent dissipation coefficient (γK) for the K coordinate are investigated. The presented results demonstrate that an impact of the ks and γK parameters on the calculated observable fission characteristics can be selectively probed. It was found that it is possible to describe the experimental data consistently with the deformation-dependent γK(q) coefficient for shapes featuring a neck, which predicts quite small values of γK=0.0077 (MeV zs)-1/2 and constant γK=0.1-0.4 (MeV zs)-1/2 for compact shapes featuring no neck.

  16. Data consistencies of swift heavy ion induced damage creation in yttrium iron garnet analyzed by different techniques

    NASA Astrophysics Data System (ADS)

    Meftah, A.; Benhacine, H.; Benyagoub, A.; Grob, J. J.; Izerrouken, M.; Kadid, S.; Khalfaoui, N.; Stoquert, J. P.; Toulemonde, M.; Trautmann, C.

    2016-01-01

    Pronounced swelling is observed when single crystals of yttrium iron garnet Y3Fe5O12 (YIG) are irradiated in the electronic energy loss regime with various swift heavy ions. The out-of-plane swelling was measured by scanning across the border line between an irradiated and a virgin area of the sample surface with the tip of a profilometer. The step height varied between 20 and 600 nm depending on fluence, electronic energy loss and total range of the ions. The step height divided by the ion range as a function of the ion fluence exhibits a linear increase in the initial phase and saturates at high fluences leading to a density decrease of around 1.7%. With complementary channeling-Rutherford-backscattering experiments (c-RBS), the damage fraction and the corresponding damage cross section were extracted and compared to the cross section deduced from swelling measurements. Irradiation effects were also characterized by scanning force microscopy (SFM). A threshold for damage creation as deduced from all the present physical characterizations is 5.5 ± 1.0 keV/nm. The value is in full agreement with previous measurements confirming that swelling and SFM characterizations can provide information concerning the electronic energy loss threshold for track formation. In contrast, track radii deduced from swelling measurements are smaller and radii from SFM are larger than deduced from c-RBS analysis. The results of Y3Fe5O12 of this work are compared with data obtained for other crystalline oxides and for ionic crystals.

  17. A comparison of heavy ion induced single event upset susceptibility in unhardened 6T/SRAM and hardened ADE/SRAM

    NASA Astrophysics Data System (ADS)

    Wang, Bin; Zeng, Chuanbin; Geng, Chao; Liu, Tianqi; Khan, Maaz; Yan, Weiwei; Hou, Mingdong; Ye, Bing; Sun, Youmei; Yin, Yanan; Luo, Jie; Ji, Qinggang; Zhao, Fazhan; Liu, Jie

    2017-09-01

    Single event upset (SEU) susceptibility of unhardened 6T/SRAM and hardened active delay element (ADE)/SRAM, fabricated with 0.35 μm silicon-on-insulator (SOI) CMOS technology, was investigated at heavy ion accelerator. The mechanisms were revealed by the laser irradiation and resistor-capacitor hardened techniques. Compared with conventional 6T/SRAM, the hardened ADE/SRAM exhibited higher tolerance to heavy ion irradiation, with an increase of about 80% in the LET threshold and a decrease of ∼64% in the limiting upset cross-section. Moreover, different probabilities between 0 → 1 and 1 → 0 transitions were observed, which were attributed to the specific architecture of ADE/SRAM memory cell. Consequently, the radiation-hardened technology can be an attractive alternative to the SEU tolerance of the device-level.

  18. Adaptive response of low linear energy transfer X-rays for protection against high linear energy transfer accelerated heavy ion-induced teratogenesis.

    PubMed

    Wang, Bing; Ninomiya, Yasuharu; Tanaka, Kaoru; Maruyama, Kouichi; Varès, Guillaume; Eguchi-Kasai, Kiyomi; Nenoi, Mitsuru

    2012-12-01

    Adaptive response (AR) of low linear energy transfer (LET) irradiations for protection against teratogenesis induced by high LET irradiations is not well documented. In this study, induction of AR by X-rays against teratogenesis induced by accelerated heavy ions was examined in fetal mice. Irradiations of pregnant C57BL/6J mice were performed by delivering a priming low dose from X-rays at 0.05 or 0.30 Gy on gestation day 11 followed one day later by a challenge high dose from either X-rays or accelerated heavy ions. Monoenergetic beams of carbon, neon, silicon, and iron with the LET values of about 15, 30, 55, and 200 keV/μm, respectively, were examined. Significant suppression of teratogenic effects (fetal death, malformation of live fetuses, or low body weight) was used as the endpoint for judgment of a successful AR induction. Existence of AR induced by low-LET X-rays against teratogenic effect induced by high-LET accelerated heavy ions was demonstrated. The priming low dose of X-rays significantly reduced the occurrence of prenatal fetal death, malformation, and/or low body weight induced by the challenge high dose from either X-rays or accelerated heavy ions of carbon, neon or silicon but not iron particles. Successful AR induction appears to be a radiation quality event, depending on the LET value and/or the particle species of the challenge irradiations. These findings would provide a new insight into the study on radiation-induced AR in utero. © 2012 Wiley Periodicals, Inc.

  19. Swift heavy ion induced structural and optical properties of Y{sub 2}O{sub 3}:Eu{sup 3+} nanophosphor

    SciTech Connect

    Som, S.; Sharma, S.K.; Lochab, S.P.

    2013-02-15

    Highlights: ► Europium doped yttrium oxide nanophosphor was synthesized via combustion method. ► Prepared nanophosphor was irradiated by 150 MeV Swift heavy ion (Ni{sup 7+}). ► Structural (XRD, FTIR, and TEM) and optical properties (DR and PL) after ion irradiation were studied. ► Band gap increases with ion fluence due to the decrease in average crystallite size. -- Abstract: This paper reports the structural and optical modifications of Y{sub 2}O{sub 3}:Eu{sup 3+} nanophosphor induced by 150 MeV Ni{sup 7+} swift heavy ions (SHI) in the fluence range 1 × 10{sup 11} to 1 × 10{sup 13} ions/cm{sup 2}. The XRD, TEM and FTIR studies confirm the loss of crystallinity of the nanophosphors after ion irradiation. Diffuse reflectance spectrum shows a blue shift in the absorption band for SHI induced nanophosphors. An increase in the intensity of photoluminescence peaks without any shift in the peak positions was observed.

  20. 100 MeV Ni{sup +7} swift heavy ion induced magnetism in cobalt doped ZnO thin films

    SciTech Connect

    Kumar, Sunil Singh, D. P.; Kumar, Ravi

    2014-04-24

    Zn{sub 0.90}Co{sub 0.10}O thin films were prepared using Sol-Gel spin coating method. Films were irradiated with 100 MeV Ni{sub +7} Swift Heavy Ions (SHI) with fluences 1× 10{sup 13} ions/cm{sup 2} using 15 UD tandem accelerator at IUAC New Delhi and its effect were studied on the structural, optical and magnetic properties of irradiated thin films. X-ray diffraction studies show single phase films with preferred c-axis orientation after irradiation. Ultraviolet-visible absorption spectroscopy shows red shift in the band gap of irradiated thin films. Magnetic field dependence of magnetization reveals weak ferromagnetism in irradiated thin films. AFM studies shows significant increase in the grain size and the surface roughness of the films after irradiation.

  1. Heavy ion-induced lesions in DNA: A theoretical model for the initial induction of DNA strand breaks and chromatin breaks

    SciTech Connect

    Schmidt, J.B.

    1993-01-01

    A theoretical model has been developed and used to calculate yields and spatial distributions of DNA strand breaks resulting from the interactions of heavy ions with chromatin in aqueous systems. The three dimensional spatial distribution of ionizing events has been modeled for charged particles as a function of charge and velocity. Chromatin has been modeled as a 30 nm diameter solenoid of nucleosomal DNA. The Monte Carlo methods used by Chatterjee et al. have been applied to DNA in a chromatin conformation. Refinements to their methods include: a combined treatment of primary and low energy (<2 keV) secondary electron interactions, an improved low energy delta ray model, and the combined simulation of direct energy deposition on the DNA and attack by diffusing hydroxyl radicals. Individual particle tracks are treated independently, which is assumed to be applicable to low fluence irradiations in which multiple particle effects are negligible. Single strand break cross section [open quotes]hooks[close quotes] seen in experiments at very high LET appear to be due to the collapsing radial extent of the track, as predicted in the [open quotes]deep sieve[close quotes] hypothesis proposed by Tobias et al. Spatial distributions of lesions produced by particles have been found to depend on chromatin structure. In the future, heavy ions may be used as a tool to probe the organization of DNA in chromatin. A Neyman A-binomial variation of the [open quotes]cluster model[close quotes] for the distribution of chromatin breaks per irradiated cell has been theoretically tested. The model includes a treatment of the chromatin fragment detection technique's resolution, which places a limitation on the minimum size of fragments which can be detected. The model appears to fit some of the experimental data reasonably well. However, further experimental and theoretical refinements are desirable.

  2. Microsatellite instability in human mammary epithelial cells transformed by heavy ions

    NASA Astrophysics Data System (ADS)

    Yanada, S.; Yang, T. C.; George, K.; Okayasu, R.; Ando, K.; Tsujii, H.

    1998-11-01

    We analyzed DNA and proteins obtained from normal and transformed human mammary epithelial cells for studying the neoplastic transformation by high-LET irradiation in vitro. We also examined microsatellite instability in human mammary cells transformed to various stages of carcinogenesis, such as normal, growth variant and tumorigenic, using microsatellite marker D5S177 on the chromosome 5 and CY17 on the Chromosome 10. Microsatellite instabilities were detected in the tumorigenic stage. These results suggest that microsatellite instability may play a role in the progression of tumorigenecity. The cause of the genomic instability has been suggested as abnormalities of DNA-repair systems which may be due to one of the three reasons: 1) alterations of cell cycle regulating genes. 2) mutations in any of the DNA mismatch repair genes, 3) mutation in any of the DNA strand breaks repair genes. No abnormality of these genes and encoded proteins, however was found in the present studies. These studies thus suggest that the microsatellite instability is induced by an alternative mechanism.

  3. Incorporation of a tilting coordinate into the multidimensional Langevin dynamics of heavy-ion-induced fission: Analysis of experimental data from fusion-fission reactions

    NASA Astrophysics Data System (ADS)

    Nadtochy, P. N.; Ryabov, E. G.; Gegechkori, A. E.; Anischenko, Yu. A.; Adeev, G. D.

    2014-01-01

    A four-dimensional dynamical model was developed and applied to study fission characteristics in a wide range of a fissility parameter. Three collective shape coordinates and the K coordinate were considered dynamically from the ground-state deformation to the scission into fission fragments. A modified one-body mechanism for nuclear dissipation with a reduction coefficient ks of the contribution from a "wall" formula has been used in the study. The inclusion of the K coordinate in the dynamical consideration and use of the "chaos-weighted wall formula" with a deformation-dependent scaling factor ks(q1) lead to fairly good reproduction of the variances of the fission-fragment mass distribution and the prescission neutron multiplicity for a number of fissioning compound nuclei in a wide fissility range. The four-dimensional dynamical calculations describe better experimental prescission neutron multiplicity and variances of fission-fragment mass distribution for heaviest nuclei with respect to a three-dimensional dynamical model, where the K coordinate is assumed to be equal to zero. The estimate of a dissipation coefficient for the orientation degree of freedom, γK≃0.077 (MeVzs)-1/2, is good for heavy nuclei and a larger value of γK≃0.2 (MeVzs)-1/2 is needed for nuclei with mass ACN ≃ 200.

  4. Ion-induced nuclear radiotherapy

    DOEpatents

    Horn, Kevin M.; Doyle, Barney L.

    1996-01-01

    Ion-induced Nuclear Radiotherapy (INRT) is a technique for conducting radiosurgery and radiotherapy with a very high degree of control over the spatial extent of the irradiated volume and the delivered dose. Based upon the concept that low energy, ion induced atomic and nuclear reactions can be used to produce highly energetic reaction products at the site of a tumor, the INRT technique is implemented through the use of a conduit-needle or tube which conducts a low energy ion beam to a position above or within the intended treatment area. At the end of the conduit-needle or tube is a specially fabricated target which, only when struck by the ion beam, acts as a source of energetic radiation products. The inherent limitations in the energy, and therefore range, of the resulting reaction products limits the spatial extent of irradiation to a pre-defined volume about the point of reaction. Furthermore, since no damage is done to tissue outside this irradiated volume, the delivered dose may be made arbitrarily large. INRT may be used both as a point-source of radiation at the site of a small tumor, or as a topical bath of radiation to broad areas of diseased tissue.

  5. Ion-induced nuclear radiotherapy

    DOEpatents

    Horn, K.M.; Doyle, B.L.

    1996-08-20

    Ion-induced Nuclear Radiotherapy (INRT) is a technique for conducting radiosurgery and radiotherapy with a very high degree of control over the spatial extent of the irradiated volume and the delivered dose. Based upon the concept that low energy, ion induced atomic and nuclear reactions can be used to produce highly energetic reaction products at the site of a tumor, the INRT technique is implemented through the use of a conduit-needle or tube which conducts a low energy ion beam to a position above or within the intended treatment area. At the end of the conduit-needle or tube is a specially fabricated target which, only when struck by the ion beam, acts as a source of energetic radiation products. The inherent limitations in the energy, and therefore range, of the resulting reaction products limits the spatial extent of irradiation to a pre-defined volume about the point of reaction. Furthermore, since no damage is done to tissue outside this irradiated volume, the delivered dose may be made arbitrarily large. INRT may be used both as a point-source of radiation at the site of a small tumor, or as a topical bath of radiation to broad areas of diseased tissue. 25 figs.

  6. Mammary tumors

    SciTech Connect

    Weller, R.E.

    1988-10-01

    Mammary neoplasia is one of the more common malignancies affecting domestic species. Despite their importance, they are often over- diagnosed, undertreated and subject to several misconceptions propagated by veterinarians and pet owners alike. Mammary neoplasia is the most frequent tumor type encountered in the female accounting for almost half of all malignancies reported. The canine has the highest incidence of mammary tumors of all domestic species. In the dog, about 65 percent of mammary tumors are benign mixed tumors, and 25 percent are carcinomas. The rest are adenomas, myoepitheliomas, and malignant mixed tumors. The age distribution of mammary tumors closely follows the age distribution of most tumors in the dog. Mammary tumors are rare in dogs 2 years old, but incidence begins to increase sharply at approximately 6 years of age. Median age at diagnosis is about 10 years. No breed predilection has been consistently reported.

  7. Do toxic ions induce hormesis in plants?

    PubMed

    Poschenrieder, Charlotte; Cabot, Catalina; Martos, Soledad; Gallego, Berta; Barceló, Juan

    2013-11-01

    The concept of hormesis in plants is critically reviewed, taking growth stimulation by low concentrations of toxic trace elements as a reference. The importance of both non-adaptive and adaptive mechanisms underlying ion-induced hormetic growth responses is highlighted. The activation of defense mechanisms by metal ions and pathogenic elicitors and the cross talk between the signals induced by metal ions and biotic stressors are considered. The production of reactive oxygen species and, consequently, the induction of stress-induced antioxidants, are key mechanisms in metal ion-induced hormesis in plants. It is concluded that in the current scientific literature, hormesis is used as an "umbrella" term that includes a wide range of different mechanisms. It is recommended that the term hormesis be used in plant toxicology as a descriptive term for the stimulated phase in growth response curves that is induced by low concentrations of toxic metal ions without evidence of the underlying mechanisms. If the mechanisms underlying the stimulated growth phase have been identified, specific terms, such as amelioration, defense gene activation, priming or acclimation, should be used. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Atmospheric Ion-induced Aerosol Nucleation

    NASA Astrophysics Data System (ADS)

    Curtius, J.; Lovejoy, E. R.; Froyd, K. D.

    2006-08-01

    Ion-induced nucleation has been suggested to be a potentially important mechanism for atmospheric aerosol formation. Ions are formed in the background atmosphere by galactic cosmic rays. A possible connection between galactic cosmic rays and cloudiness has been However, the predictions of current atmospheric nucleation models are highly uncertain because the models are usually based on the liquid drop model that estimates cluster thermodynamics based on bulk properties (e.g., liquid drop density and surface tension). Sulfuric acid (H2SO4) and water are assumed to be the most important nucleating agents in the free troposphere. Measurements of the molecular thermodynamics for the growth and evaporation of cluster ions containing H2SO4 and H2O were performed using a temperature-controlled laminar flow reactor coupled to a linear quadrupole mass spectrometer as well as a temperature-controlled ion trap mass spectrometer. The measurements were complemented by quantum chemical calculations of the cluster ion structures. The analysis yielded a complete set of H2SO4 and H2O binding thermodynamics extending from molecular cluster ions to the bulk, based on experimental thermodynamics for the small clusters. The data were incorporated into a kinetic aerosol model to yield quantitative predictions of the rate of ion-induced nucleation for atmospheric conditions. The model predicts that the negative ion-H2SO4-H2O nucleation mechanism is an efficient source of new particles in the middle and upper troposphere.

  9. High Relative Biologic Effectiveness of Carbon Ion Radiation on Induction of Rat Mammary Carcinoma and its Lack of H-ras and Tp53 Mutations

    SciTech Connect

    Imaoka, Tatsuhiko Nishimura, Mayumi; Kakinuma, Shizuko; Hatano, Yukiko; Ohmachi, Yasushi; Yoshinaga, Shinji Ph.D.; Kawano, Akihiro; Maekawa, Akihiko; Shimada, Yoshiya

    2007-09-01

    Purpose: The high relative biologic effectiveness (RBE) of high-linear energy transfer (LET) heavy-ion radiation has enabled powerful radiotherapy. The potential risk of later onset of secondary cancers, however, has not been adequately studied. We undertook the present study to clarify the RBE of therapeutic carbon ion radiation and molecular changes that occur in the rat mammary cancer model. Methods and Materials: We observed 7-8-week-old rats (ACI, F344, Wistar, and Sprague-Dawley) until 1 year of age after irradiation (0.05-2 Gy) with either 290 MeV/u carbon ions with a spread out Bragg peak (LET 40-90 keV/{mu}m) generated from the Heavy-Ion Medical Accelerator in Chiba or {sup 137}Cs {gamma}-rays. Results: Carbon ions significantly induced mammary carcinomas in Sprague-Dawley rats but less so in other strains. The dose-effect relationship for carcinoma incidence in the Sprague-Dawley rats was concave downward, providing an RBE of 2 at a typical therapeutic dose per fraction. In contrast, {approx}10 should be considered for radiation protection at low doses. Immunohistochemically, 14 of 18 carcinomas were positive for estrogen receptor {alpha}. All carcinomas examined were free of common H-ras and Tp53 mutations. Importantly, lung metastasis (7%) was characteristic of carbon ion-irradiated rats. Conclusions: We found clear genetic variability in the susceptibility to carbon ion-induced mammary carcinomas. The high RBE for carbon ion radiation further supports the importance of precise dose localization in radiotherapy. Common point mutations in H-ras and Tp53 were not involved in carbon ion induction of rat mammary carcinomas.

  10. Helium-ion-induced human cataractogenesis

    NASA Technical Reports Server (NTRS)

    Blakely, E. A.; Daftari, I. K.; Meecham, W. J.; Alonso, L. C.; Collier, J. M.; Kroll, S. M.; Gillette, E. L.; Lee, A. C.; Lett, J. T.; Cox, A. B.

    1994-01-01

    Retrospective and ongoing analyses of clinical records from 347 primary intraocular melanoman patients treated with helium ions at Lawrence Berkeley Laboratory (LBL) will allow examination of the exposure-response data for human cataract; which is a complication of the therapy from incidental exposure of the lens. Direct particle beam traversal of at least a portion of the lens usually is unavoidable in treatment of posterior intraocular tumors. The precise treatment planned for each patient permits quantitative assessment of the lenticular dose and its radiation quality. We are reporting our preliminary results on the development of helium-ion-induced lens opacifications and cataracts in 54 of these patients who had 10% or less of their lens in the treatment field. We believe these studies will be relevant to estimating the human risk for cataract in space flight.

  11. Light-ion-induced multifragmentation: The ISiS project

    NASA Astrophysics Data System (ADS)

    Viola, V. E.; Kwiatkowski, K.; Beaulieu, L.; Bracken, D. S.; Breuer, H.; Brzychczyk, J.; de Souza, R. T.; Ginger, D. S.; Hsi, W.-C.; Korteling, R. G.; Lefort, T.; Lynch, W. G.; Morley, K. B.; Legrain, R.; Pienkowski, L.; Pollacco, E. C.; Renshaw, E.; Ruangma, A.; Tsang, M. B.; Volant, C.; Wang, G.; Yennello, S. J.; Yoder, N. R.

    2006-11-01

    An extensive study of GeV light-ion-induced multifragmentation and its possible interpretation in terms of a nuclear liquid-gas phase transition has been performed with the Indiana Silicon Sphere (ISiS) 4π detector array. Measurements were performed with 5-15 GeV/ c p, pbar, and π- beams incident on 197Au and 2-5 GeV 3He incident on natAg and 197Au targets. Both the reaction dynamics and the subsequent decay of the heavy residues have been explored. The data provide evidence for a dramatic change in the reaction observables near an excitation energy of E*/A=4-5 MeV/residue nucleon. In this region, fragment multiplicities and energy spectra indicate emission from an expanded/dilute source on a very short time scale (20-50 fm/ c). These properties, along with caloric curve and scaling-law behavior, yield a pattern that is consistent with a nuclear liquid-gas phase transition.

  12. Ion induced deformation of soft tissue.

    PubMed

    Myers, T G; Aldis, G K; Naili, S

    1995-01-01

    In this paper the effects of changing the ion concentration in and around a sample of soft tissue are investigated. The triphasic theory developed by Lai et al. (1990, Biomechanics of Diarthrodial Joints, Vol. 1, Berlin, Springer-Verlag) is reduced to two coupled partial differential equations involving fluid ion concentration and tissue solid deformation. These equations are given in general form for Cartesian, cylindrical and spherical geometries. After solving the two equations quantities such as fluid velocity, fluid pressure, chemical potentials and chemical expansion stress may be easily calculated. In the Cartesian geometry comparison is made with the experimental and theoretical work of Myers et al. (1984, ASME J. biomech. Engng, 106, 151-158). This dealt with changing the ion concentration of a salt shower on a strip of bovine articular cartilage. Results were obtained in both free swelling and isometric tension states, using an empirical formula to account for ion induced deformation. The present theory predicts lower ion concentrations inside the tissue than this earlier work. A spherical sample of tissue subjected to a change in salt bath ion concentration is also considered. Numerical results are obtained for both hypertonic and hypotonic bathing solutions. Of particular interest is the finding that tissue may contract internally before reaching a final swollen equilibrium state or swell internally before finally contracting. By considering the relative magnitude, and also variation throughout the time course of terms in the governing equations, an even simpler system is deduced. As well as being linear the concentration equation in the new system is uncoupled. Results obtained from the linear system compare well with those from the spherical section. Thus, biological swelling situations may be modelled by a simple system of equations with the possibility of approximate analytic solutions in certain cases.

  13. Ion-Induced Nucleation Under Atmospheric Conditions

    NASA Astrophysics Data System (ADS)

    Pedersen, J. O.; Svensmark, H.; Enghoff, M. B.

    2007-12-01

    Experimental studies of aerosol nucleation in air, containing trace amounts of ozone, sulphur dioxide, and water vapor at concentrations relevant for the Earths atmosphere are reported. The production of new aerosol particles is found to be proportional to the negative ion density. These results suggest that ions are important for nucleation processes in the atmosphere and cloud cover -- and may thus link cosmic rays to Earth's climate. The production of aerosols in the Earth's atmosphere is an unresolved and challenging problem. Atmospheric and experimental observations have shown that the nucleation of aerosol particles can occur under conditions that cannot be explained by classical nucleation theory. Several ideas have been put forward to solve the nucleation problem, e.g., Ion-induced Nucleation and Ternary Nucleation. However, experimental investigations exploring the role of ions in particle production are scarce, and often at conditions far removed from those relevant for the lower part of the atmosphere. In our laboratory we have performed1 an experimental investigation of nucleation that confirms the importance of ions under conditions that do prevail in the lower atmosphere. The measurements were performed in a 7 m3 reaction chamber, which was continuously flushed with dry purified air. Variable concentrations of water vapor (H2O), ozone (O3), and sulphur dioxide (SO2) could be added to the chamber, where the pressure was held a few Pa above atmospheric pressure, and the temperature fixed at 296 K. UV-lamps (253.7 nm) were used to initiate a photochemical reaction that transforms (H2O), ozone (O3), and sulphur dioxide (SO2) to sulphuric acid (H2SO4). Ions were produced in the chamber by galactic cosmic radiation. This natural production of ions could be enhanced with gamma sources, mounted outside of the chamber. A Gerdien tube was used to measure the ion current, and aerosols generated in the chamber were measured with a TSI Ultra Fine Condensation

  14. Ion-Induced Electron Emission from Metals

    NASA Astrophysics Data System (ADS)

    Kirchhoff, Joseph Francis

    1992-01-01

    Ion-induced electron emission (IIEE) from several metals under 100 keV proton bombardment has been investigated. Room temperature (RT) yields, i.e., the number of electrons emitted per incident ion, were measured for gold, copper, and indium after sputter cleaning and agreed with published values. New experimental results indicate a lowering of the RT yield after ultra-high vacuum anneals and very light sputtering. Previously published RT yields, gamma _{rm sputtered}, were measured only after extensive sputter cleaning. Copper, after an anneal near 390^circC, had a room temperature gamma_{rm anneal} = 1.58 +/- 0.02 e^-/ion with gamma _{rm sputtered} = 1.77 +/- 0.02 e^-/ion. The yield for solid indium after melting and resolidification was measured as gamma_{rm anneal} = 1.69 +/- 0.02 e^-/ion with gamma _{rm sputtered} = 1.95 +/- 0.03 e^-/ion. It is believed that annealing orders the surface, while gamma_{rm sputtered} yield values are from disordered surfaces. Yield data as a function of target temperature were also measured. For copper and indium, yields were found to vary linearly with temperature up to at least 330^circC for Cu and 195 ^circC for In. The dgamma/ dT values found were 2.7 +/- 0.2 times 10^{ -4} and 3.3 +/- 0.3 times 10^{-4} e^-/ion/K, respectively. Yields for liquid indium and through the melting transition were also measured. UHV yields for liquid metals have not been reported before. After melting, no change was found in the yield (|Deltagamma/gamma |<0.2%). A semi-empirical model for the yields in nearly free electron metals has been developed and is based on the formalism of Sigmund and Tougaard. It suggests a strong dependence of yield on the surface potential barrier, U, which must be overcome for emission. The dependence of gamma on U^{ -2.5} has not been previously realized. The model explains yields measured by others, as well as the temperature dependent yield phenomena observed in this study. It also predicts relatively large yields

  15. Verification of difference of ion-induced nucleation rate for kinds of ionizing radiation

    NASA Astrophysics Data System (ADS)

    Suzuki, A.; Masuda, K.; Takeuchi, Y.; Itow, Y.; Sako, T.; Matsumi, Y.; Nakayama, T.; Ueda, S.; Miura, K.; Kusano, K.

    2014-12-01

    Correlation between the global cloud cover and the galactic cosmic rays intensity has been pointed out. So as one of hypotheses, the promotion of creation of cloud condensation nuclei by cosmic rays can be considered. In this study, we have carried out verification experiment of this hypothesis using an atmospheric reaction chamber at room temperature focusing on the kind of ionizing radiation. We introduced pure air, a trace of water vapor, ozone and sulfur dioxide gas in a chamber with a volume of 75[L]. The sulfur dioxide reacts chemically in the chamber to form sulfate aerosol. After introducing the mixed gas into the chamber, it was irradiated with ultraviolet light, which simulate solar ultraviolet radiation and with anthropogenic ionizing radiation for cosmic rays, particles and new particle formation due to ion-induced nucleation was observed by measuring and recording the densities of ions and aerosol particles, the particle size distribution, the concentrations of ozone and sulfur dioxide, the temperature and the relative humidity. Here, the experimental results of aerosol nucleation rate for different types of radiation are reported. In this experiment, we conducted experiments of irradiation with heavy ions and β-rays. For ionizing radiation Sr-90 β-rays with an average energy of about 1[MeV] and a heavy ion beam from a particle accelerator facility of HIMAC at NIRS (Heavy Ion Medical Accelerator in Chiba, National Institute of Radiological Sciences) were used. The utilized heavy ion was 14N ions of 180[MeV/n] with intensities from 200[particles/spill] to 10000[particles/spill]. In this experimental run the chamber was irradiated for 10 hours and, the relationship between aerosol particle density for the particle size of > of 2.5[nm] and the generated ion density was verified. In the middle, the chamber was irradiated with β-rays for comparison. Increases in the ion density with the increase of the beam intensity were confirmed. Also, a rise in the

  16. Presence of hyperplastic pectoral mammary glands in a white-footed mouse (Peromyscus leucopus) from a Superfund Site in Oklahoma, USA.

    PubMed

    Hays, Kimberly A; Breshears, Melanie A

    2011-01-01

    Laboratory experiments have documented the effects of hormones and endocrine-disrupting compounds on mammary development in mammals. However, few observations of mammary hyperplasia have been presented for wild rodents. We describe hyperplastic mammary glands in a wild-caught white-footed mouse (Peromyscus leucopus) from an area contaminated with heavy metals.

  17. Silicon Carbide Power Device Performance Under Heavy-Ion Irradiation

    NASA Technical Reports Server (NTRS)

    Lauenstein, Jean-Marie; Casey, Megan; Topper, Alyson; Wilcox, Edward; Phan, Anthony; Ikpe, Stanley; LaBel, Ken

    2015-01-01

    Heavy-ion induced degradation and catastrophic failure data for SiC power MOSFETs and Schottky diodes are examined to provide insight into the challenge of single-event effect hardening of SiC power devices.

  18. Mammary Duct Ectasia

    MedlinePlus

    ... tenderness or inflammation of the clogged duct (periductal mastitis). Mammary duct ectasia most often occurs in women ... that's turned inward (inverted) A bacterial infection called mastitis also may develop in the affected milk duct, ...

  19. Helium-ion-induced release of hydrogen from graphite

    SciTech Connect

    Langley, R.A.

    1987-01-01

    The ion-induced release of hydrogen from AXF-5Q graphite was studied for 350-eV helium ions. The hydrogen was implanted into the graphite with a low energy (approx.200 eV) and to a high fluence. This achieved a thin (approx.10-nm), saturated near-surface region. The release of hydrogen was measured as a function of helium fluence. A model that includes ion-induced detrapping, retrapping, and surface recombination was used to analyze the experimental data. A value of (1.65 +- 0.2) x 10/sup -16/ cm/sup 2/ was obtained from the detrapping cross section, and a value of (0.5 to 4) x 10/sup -14/ cm/sup 4//atoms was obtained for the recombination coefficient. 11 refs., 4 figs.

  20. Thermodynamic analysis of metal ion-induced protein assembly.

    PubMed

    Herr, Andrew B; Conrady, Deborah G

    2011-01-01

    A large number of biological systems are regulated by metal ion-induced protein assembly. This phenomenon can play a critical role in governing protein function and triggering downstream biological responses. We discuss the basic thermodynamic principles of linked equilibria that pertain to metal ion-induced dimerization and describe experimental approaches useful for studying such systems. The most informative techniques for studying these systems are sedimentation velocity and sedimentation equilibrium analytical ultracentrifugation, although a wide range of other spectroscopic, chromatographic, or qualitative approaches can provide a wealth of useful information. These experimental procedures are illustrated with examples from two systems currently under study: zinc-induced assembly of a staphylococcal protein responsible for intercellular adhesion in bacterial biofilms and calcium-induced dimerization of a human nucleotidase.

  1. Modeling ion-induced electrons in the High Current Experiment

    SciTech Connect

    Stoltz, P.H.; Verboncoeur, J.P.; Cohen, R.H.; Molvik, A.W.; Vay, J.-L.; Veitzer, S.A.

    2006-05-15

    A primary concern for high current ion accelerators is contaminant electrons. These electrons can interfere with the beam ions, causing emittance growth and beam loss. Numerical simulation is a main tool for understanding the interaction of the ion beam with the contaminant electrons, but these simulations then require accurate models of electron generation. These models include ion-induced electron emission from ions hitting the beam pipe walls or diagnostics. However, major codes for modeling ion beam transport are written in different programming languages and used on different computing platforms. For electron generation models to be maximally useful, researchers should be able to use them easily from many languages and platforms. A model of ion-induced electrons including the electron energy distribution is presented here, including a discussion of how to use the Babel software tool to make these models available in multiple languages and how to use the GNU Autotools to make them available on multiple platforms. An application to simulation of the end region of the High Current Experiment is shown. These simulations show formation of a virtual cathode with a potential energy well of amplitude 12.0 eV, approximately six times the most probable energy of the ion-induced electrons. Oscillations of the virtual cathode could lead to possible longitudinal and transverse modulation of the density of the electrons moving out of the virtual cathode.

  2. Modeling ion-induced electrons in the High Current Experimenta)

    NASA Astrophysics Data System (ADS)

    Stoltz, P. H.; Verboncoeur, J. P.; Cohen, R. H.; Molvik, A. W.; Vay, J.-L.; Veitzer, S. A.

    2006-05-01

    A primary concern for high current ion accelerators is contaminant electrons. These electrons can interfere with the beam ions, causing emittance growth and beam loss. Numerical simulation is a main tool for understanding the interaction of the ion beam with the contaminant electrons, but these simulations then require accurate models of electron generation. These models include ion-induced electron emission from ions hitting the beam pipe walls or diagnostics. However, major codes for modeling ion beam transport are written in different programming languages and used on different computing platforms. For electron generation models to be maximally useful, researchers should be able to use them easily from many languages and platforms. A model of ion-induced electrons including the electron energy distribution is presented here, including a discussion of how to use the Babel software tool to make these models available in multiple languages and how to use the GNU Autotools to make them available on multiple platforms. An application to simulation of the end region of the High Current Experiment is shown. These simulations show formation of a virtual cathode with a potential energy well of amplitude 12.0eV, approximately six times the most probable energy of the ion-induced electrons. Oscillations of the virtual cathode could lead to possible longitudinal and transverse modulation of the density of the electrons moving out of the virtual cathode.

  3. Mammary gland development.

    PubMed

    Macias, Hector; Hinck, Lindsay

    2012-01-01

    The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial–mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development—pubertal growth, pregnancy, lactation, and involution—occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone (GH) and estrogen, as well as insulin-like growth factor 1 (IGF1), to create a ductal tree that fills the fat pad. Upon pregnancy, the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its prepregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease.

  4. Mammary Gland Development

    PubMed Central

    Macias, Hector

    2012-01-01

    The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial/mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development – pubertal growth, pregnancy, lactation and involution – occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone and estrogen, as well as IGF1, to create a ductal tree that fills the fat pad. Upon pregnancy the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its pre-pregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease. PMID:22844349

  5. Mammary cancers and pregnancy.

    PubMed Central

    Anderson, J M

    1979-01-01

    Uncertainties persist about management and prognosis of mammary cancers that occur during and after pregnancy and during lactation. Pathological features of mammary cancers occurring during pregnancy are the same as those in non-pregnant women and survival rates are comparable. Management should be the same as in non-pregnant patients. Termination of pregnancy does not improve survival but it should be advised if the prognosis is poor. Mastectomy apparently presents little danger to the fetus, though treatment such as chemotherapy and irradiation should be avoided. Women who have received treatment for mammary cancer need not be advised against subsequent pregnancy. Routine ovarian radiation in non-pregnant premenopausal women is not generally to be recommended, since it does not prolong survival and would deprive some of the chance of further pregnancy. In lactating women who develop mammary cancers survival is apparently not adversely affected. Lactation should be suppressed initially and followed by mastectomy. Regimens of immunotherapy, chemotherapy, or radiotherapy may then be begun. Until results of current trials of combined treatments of mammary cancers associated with pregnancy are available, management should be neither aggressive nor tentative. It should be based on a well-balanced concept of applying all available treatments, as in non-pregnant patients. PMID:376044

  6. Ion-induced nucleation in a binary mixture

    NASA Technical Reports Server (NTRS)

    Smith, A. C.; Singh, J. J.; Yue, G. K.; Chan, L. Y.

    1982-01-01

    Recent ion-induced nucleation studies in a binary mixture of H2O and H2SO4 vapors indicate that conventional classical nucleation theories cannot account for the experimentally observed ion-H2O-H2SO4 microcluster spectra. An empirical-analytical, semi-molecular theory of nucleation of a binary mixture of vapors on ions has been developed. This theory includes molecular approach to ion-induced changes in dielectric properties in the immediate neighborhood of an ion core as well as the size dependence of the surface tension of the microcluster. In addition to gaseous sulfuric acid and water molecules, the effect of ion-hydrates and sulfuric acid hydrates has also been considered. This theory is further simplified by using an empirical correction factor for the electrostatic term. This correction factor has been obtained by comparing the simplified model with the molecular dynamics calculations for selected ion hydrate formation. These two theoretical models are then compared with the classical theory for a variety of experimental conditions.

  7. Internal mammary artery.

    PubMed

    Calafiore, Antonio M; Weltert, Luca; Mauro, Michele Di; Actis-Dato, Guglielmo; Iacò, Angela L; Centofanti, Paolo; Torre, Michele La; Patanè, Francesco

    2005-01-01

    The internal mammary artery (IMA) has been already used in some pioneering experiences since the middle of last century but it became the graft of choice only in the 1980s, after widespread angiographic and clinical demonstration of its superiority over the saphenous vein graft (SVG). The use of both mammary arteries was then explored in order to achieve better long-term results when compared to single IMA and SVG. The IMA can be harvested pedicled or skeletonized and used as an in situ graft or as a source for composite graft (Y-graft, lengthened graft). When the bilateral internal mammary artery (BIMA) is grafted in situ, the left internal mammary artery (LIMA) is generally used for the left descending artery (LAD) and the RIMA for the right coronary artery (RCA), or for the lateral wall, usually going through the transverse sinus. In the case of Y-graft, the left coronary system is more frequently chosen as the target site of revascularization. Our experience shows that: (1) The use of IMA provides better 15-year clinical results when compared to SVG. (2) The use of BIMA in patients younger than 75 years can produce higher 10-year freedom from cardiac-related events than the single one, even in diabetic patients.

  8. Canine mammary gland tumors.

    PubMed

    Sorenmo, Karin

    2003-05-01

    The National Consensus Group recommends that all women with tumors larger than 1 cm be offered chemotherapy regardless of tumor histology of lymph node status. This recommendation is to ensure that everyone at risk for failing, even though the risk may be low in women with relatively small tumors and favorable histology, has a choice and receives the benefit of adjuvant chemotherapy. This type of treatment recommendation may also be made in dogs based on recognized, well-accepted prognostic factors such as tumor size, stage, type, and histologic differentiation. Based on the limited clinical information available in veterinary medicine, the drugs that are effective in human breast cancer, such as cyclophosphamide, 5-fluorouracil, and doxorubicin, may also have a role in the treatment of malignant mammary gland tumors in dogs. Randomized prospective studies are needed, however, to evaluate the efficacy of chemotherapy in dogs with high-risk mammary gland tumors and to determine which drugs and protocols are the most efficacious. Until such studies are performed, the treatment of canine mammary gland tumors will be based on the individual oncologist's understanding of tumor biology, experience, interpretation of the available studies, and a little bit of gut-feeling. Table 2 is a proposal for treatment guidelines for malignant canine mammary gland tumors according to established prognostic factors, results from published veterinary studies, and current recommendations for breast cancer treatment in women.

  9. Ion-induced nanopattern propagation on metallic surfaces

    NASA Astrophysics Data System (ADS)

    Škereň, Tomáš; Veselý, Martin; Čapek, Pavel; Král, Jaroslav

    2015-12-01

    We investigate the formation of ion-induced patterns on single-crystalline Ni(001) bombarded with a 20 -keV Ga+ ion beam. For near normal ion incidence isotropic roughness forms on the surface. By moving to grazing incidence this pattern gradually transforms into a pronounced ripple pattern with wave vector perpendicular to the ion beam. By using an in situ scanning electron microscope we were able to analyze the real-time dynamics of the pattern formation process and evaluate the direction and velocity of the net in-plane morphology propagation for different angles of ion incidence. We compare the experimental results to the predictions of the classical theory for the pattern formation.

  10. Humanization of the mouse mammary gland.

    PubMed

    Wronski, A; Arendt, L M; Kuperwasser, Charlotte

    2015-01-01

    Although mouse models have provided invaluable information on the mechanisms of mammary gland development, anatomical and developmental differences between human and mice limit full understanding of this fundamental process. Humanization of the mouse mammary gland by injecting immortalized human breast stromal cells into the cleared murine mammary fat pad enables the growth and development of human mammary epithelial cells or tissue. This facilitates the characterization of human mammary gland development or tumorigenesis by utilizing the mouse mammary fat pad. Here we describe the process of isolating human mammary stromal and epithelial cells as well as their introduction into the mammary fat pads of immunocompromised mice.

  11. A mammary repopulating cell population characterized in mammary anlagen reveals essential mammary stroma for morphogenesis.

    PubMed

    Song, Jiazhe; Xue, Kai; She, Ji; Ding, Fangrong; Li, Song; Shangguan, Rulan; Dai, Yunping; Du, Liying; Li, Ning

    2014-09-10

    The cells with mammary repopulating capability can achieve mammary gland morphogenesis in a suitable cellular microenvironment. Using cell surface markers of CD24, CD29 and CD49f, mouse mammary repopulating unit (MRU) has been identified in adult mammary epithelium and late embryonic mammary bud epithelium. However, embryonic MRU remains to be fully characterized at earlier mammary anlagen stage. Here we isolated discrete populations of E14.5 mouse mammary anlagen cells. Only Lin(-)CD24(med)CD29(+) cell population was predicted as E14.5 MRU by examining their capacities of forming mammosphere and repopulating cleared mammary fat pad in vivo. However, when we characterized gene expressions of this E14.5 cell population by comparing with adult mouse MRU (Lin(-)CD24(+)CD29(hi)), the gene profiling of these two cell populations exhibited great differences. Real-time PCR and immunostaining assays uncovered that E14.5 Lin(-)CD24(med)CD29(+) cell population was a heterogeneous stroma-enriched cell population. Then, limiting dilutions and single-cell assays also confirmed that E14.5 Lin(-)CD24(med)CD29(+) cell population possessed low proportion of stem cells. In summary, heterogeneous Lin(-)CD24(med)CD29(+) cell population exhibited mammary repopulating ability in E14.5 mammary anlagen, implying that only suitable mammary stroma could enable mammary gland morphogenesis, which relied on the interaction between rare stem cells and microenvironment. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Physiologically activated mammary fibroblasts promote postpartum mammary cancer

    PubMed Central

    Guo, Qiuchen; Burchard, Julja; Spellman, Paul

    2017-01-01

    Women diagnosed with breast cancer within 5 years of childbirth have poorer prognosis than nulliparous or pregnant women. Weaning-induced breast involution is implicated, as the collagen-rich, immunosuppressive microenvironment of the involuting mammary gland is tumor promotional in mice. To investigate the role of mammary fibroblasts, isolated mammary PDGFRα+ cells from nulliparous and postweaning mice were assessed for activation phenotype and protumorigenic function. Fibroblast activation during involution was evident by increased expression of fibrillar collagens, lysyl oxidase, Tgfb1, and Cxcl12 genes. The ability of mammary tumors to grow in an isogenic, orthotopic transplant model was increased when tumor cells were coinjected with involution-derived compared with nulliparous-derived mammary fibroblasts. Mammary tumors in the involution-fibroblast group had increased Ly6C+ monocytes at the tumor border, and decreased CD8+ T cell infiltration and tumor cell death. Ibuprofen treatment suppressed involution-fibroblast activation and tumor promotional capacity, concurrent with decreases in tumor Ly6C+ monocytes, and increases in intratumoral CD8+ T cell infiltration, granzyme levels, and tumor cell death. In total, our data identify a COX/prostaglandin E2 (PGE2)–dependent activated mammary fibroblast within the involuting mammary gland that displays protumorigenic, immunosuppressive activity, identifying fibroblasts as potential targets for the prevention and treatment of postpartum breast cancer. PMID:28352652

  13. Ion-induced nucleation of pure biogenic particles.

    PubMed

    Kirkby, Jasper; Duplissy, Jonathan; Sengupta, Kamalika; Frege, Carla; Gordon, Hamish; Williamson, Christina; Heinritzi, Martin; Simon, Mario; Yan, Chao; Almeida, João; Tröstl, Jasmin; Nieminen, Tuomo; Ortega, Ismael K; Wagner, Robert; Adamov, Alexey; Amorim, Antonio; Bernhammer, Anne-Kathrin; Bianchi, Federico; Breitenlechner, Martin; Brilke, Sophia; Chen, Xuemeng; Craven, Jill; Dias, Antonio; Ehrhart, Sebastian; Flagan, Richard C; Franchin, Alessandro; Fuchs, Claudia; Guida, Roberto; Hakala, Jani; Hoyle, Christopher R; Jokinen, Tuija; Junninen, Heikki; Kangasluoma, Juha; Kim, Jaeseok; Krapf, Manuel; Kürten, Andreas; Laaksonen, Ari; Lehtipalo, Katrianne; Makhmutov, Vladimir; Mathot, Serge; Molteni, Ugo; Onnela, Antti; Peräkylä, Otso; Piel, Felix; Petäjä, Tuukka; Praplan, Arnaud P; Pringle, Kirsty; Rap, Alexandru; Richards, Nigel A D; Riipinen, Ilona; Rissanen, Matti P; Rondo, Linda; Sarnela, Nina; Schobesberger, Siegfried; Scott, Catherine E; Seinfeld, John H; Sipilä, Mikko; Steiner, Gerhard; Stozhkov, Yuri; Stratmann, Frank; Tomé, Antonio; Virtanen, Annele; Vogel, Alexander L; Wagner, Andrea C; Wagner, Paul E; Weingartner, Ernest; Wimmer, Daniela; Winkler, Paul M; Ye, Penglin; Zhang, Xuan; Hansel, Armin; Dommen, Josef; Donahue, Neil M; Worsnop, Douglas R; Baltensperger, Urs; Kulmala, Markku; Carslaw, Kenneth S; Curtius, Joachim

    2016-05-26

    Atmospheric aerosols and their effect on clouds are thought to be important for anthropogenic radiative forcing of the climate, yet remain poorly understood. Globally, around half of cloud condensation nuclei originate from nucleation of atmospheric vapours. It is thought that sulfuric acid is essential to initiate most particle formation in the atmosphere, and that ions have a relatively minor role. Some laboratory studies, however, have reported organic particle formation without the intentional addition of sulfuric acid, although contamination could not be excluded. Here we present evidence for the formation of aerosol particles from highly oxidized biogenic vapours in the absence of sulfuric acid in a large chamber under atmospheric conditions. The highly oxygenated molecules (HOMs) are produced by ozonolysis of α-pinene. We find that ions from Galactic cosmic rays increase the nucleation rate by one to two orders of magnitude compared with neutral nucleation. Our experimental findings are supported by quantum chemical calculations of the cluster binding energies of representative HOMs. Ion-induced nucleation of pure organic particles constitutes a potentially widespread source of aerosol particles in terrestrial environments with low sulfuric acid pollution.

  14. Ion-induced nucleation of pure biogenic particles

    NASA Astrophysics Data System (ADS)

    Kirkby, Jasper; Duplissy, Jonathan; Sengupta, Kamalika; Frege, Carla; Gordon, Hamish; Williamson, Christina; Heinritzi, Martin; Simon, Mario; Yan, Chao; Almeida, João; Tröstl, Jasmin; Nieminen, Tuomo; Ortega, Ismael K.; Wagner, Robert; Adamov, Alexey; Amorim, Antonio; Bernhammer, Anne-Kathrin; Bianchi, Federico; Breitenlechner, Martin; Brilke, Sophia; Chen, Xuemeng; Craven, Jill; Dias, Antonio; Ehrhart, Sebastian; Flagan, Richard C.; Franchin, Alessandro; Fuchs, Claudia; Guida, Roberto; Hakala, Jani; Hoyle, Christopher R.; Jokinen, Tuija; Junninen, Heikki; Kangasluoma, Juha; Kim, Jaeseok; Krapf, Manuel; Kürten, Andreas; Laaksonen, Ari; Lehtipalo, Katrianne; Makhmutov, Vladimir; Mathot, Serge; Molteni, Ugo; Onnela, Antti; Peräkylä, Otso; Piel, Felix; Petäjä, Tuukka; Praplan, Arnaud P.; Pringle, Kirsty; Rap, Alexandru; Richards, Nigel A. D.; Riipinen, Ilona; Rissanen, Matti P.; Rondo, Linda; Sarnela, Nina; Schobesberger, Siegfried; Scott, Catherine E.; Seinfeld, John H.; Sipilä, Mikko; Steiner, Gerhard; Stozhkov, Yuri; Stratmann, Frank; Tomé, Antonio; Virtanen, Annele; Vogel, Alexander L.; Wagner, Andrea C.; Wagner, Paul E.; Weingartner, Ernest; Wimmer, Daniela; Winkler, Paul M.; Ye, Penglin; Zhang, Xuan; Hansel, Armin; Dommen, Josef; Donahue, Neil M.; Worsnop, Douglas R.; Baltensperger, Urs; Kulmala, Markku; Carslaw, Kenneth S.; Curtius, Joachim

    2016-05-01

    Atmospheric aerosols and their effect on clouds are thought to be important for anthropogenic radiative forcing of the climate, yet remain poorly understood. Globally, around half of cloud condensation nuclei originate from nucleation of atmospheric vapours. It is thought that sulfuric acid is essential to initiate most particle formation in the atmosphere, and that ions have a relatively minor role. Some laboratory studies, however, have reported organic particle formation without the intentional addition of sulfuric acid, although contamination could not be excluded. Here we present evidence for the formation of aerosol particles from highly oxidized biogenic vapours in the absence of sulfuric acid in a large chamber under atmospheric conditions. The highly oxygenated molecules (HOMs) are produced by ozonolysis of α-pinene. We find that ions from Galactic cosmic rays increase the nucleation rate by one to two orders of magnitude compared with neutral nucleation. Our experimental findings are supported by quantum chemical calculations of the cluster binding energies of representative HOMs. Ion-induced nucleation of pure organic particles constitutes a potentially widespread source of aerosol particles in terrestrial environments with low sulfuric acid pollution.

  15. Ductal barriers in mammary epithelium

    PubMed Central

    Owens, Mark B; Hill, Arnold DK; Hopkins, Ann M

    2013-01-01

    Tissue barriers play an integral role in the biology and pathobiology of mammary ductal epithelium. In normal breast physiology, tight and adherens junctions undergo dynamic changes in permeability in response to hormonal and other stimuli, while several of their proteins are directly involved in mammary tumorigenesis. This review describes first the structure of mammary ductal epithelial barriers and their role in normal mammary development, examining the cyclical changes in response to puberty, pregnancy, lactation and involution. It then examines the role of adherens and tight junctions and the participation of their constituent proteins in mammary tumorigenic functions such as migration, invasion and metastasis. Finally, it discusses the potential of these adhesion proteins as both prognostic biomarkers and potential therapeutic targets in breast cancer. PMID:24665412

  16. Chemoprevention of Radiation Induced Rat Mammary Neoplasms

    NASA Technical Reports Server (NTRS)

    Huso, David L.

    1999-01-01

    Radiations encountered in space include protons and heavy ions such as iron as well as their secondaries. The relative biological effect (RBE) of these ions is not known, particularly at the doses and dose-rates expected for planetary missions. Neutrons, are not particularly relevant to space travel, but have been found experimentally to have an increase in their RBE with decreasing dose. If a similar trend of increasing RBE with decreasing dose is present for heavy ions and protons during irradiation in space, the small doses received during space travel could potentially have substantial carcinogenic risk. Clearly more investigation of the effects of heavy ions and protons is needed before accurate risk assessment for prolonged travel in space can be done. One means to mitigate the increased risk of cancer due to radiation exposure in space is by developing effective countermeasures that can reduce the incidence of tumor development. Tamoxifen has recently been shown to be an effective chemopreventive agent in both animal models and humans for the prevention of mammary tumors. Tamoxifen is a unique drug, with a highly specific mechanism of action affecting a specific radiation-sensitive population of epithelial cells in the mammary gland. In human studies, the annual incidence of a primary tumor in the contralateral breast of women with previous breast cancer is about 8 per 1000, making them an exceedingly high-risk group for the development of breast cancer. In this high risk group, treated with tamoxifen, daily, for 2 years, the incidence of a new primary tumor in the contralateral breast was approximately one third of that noted in the non-tamoxifen treatment group. Tamoxifen antagonizes the action of estrogen by competing for the nuclear receptor complex thereby altering the association of the receptor complex and nuclear binding sites. Its effects in reducing the development of breast cancer could be accomplished by controlling clinically undetectable

  17. Chemoprevention of Radiation Induced Rat Mammary Neoplasms

    NASA Technical Reports Server (NTRS)

    Huso, David L.

    1999-01-01

    Radiations encountered in space include protons and heavy ions such as iron as well as their secondaries. The relative biological effect (RBE) of these ions is not known, particularly at the doses and dose-rates expected for planetary missions. Neutrons, are not particularly relevant to space travel, but have been found experimentally to have an increase in their RBE with decreasing dose. If a similar trend of increasing RBE with decreasing dose is present for heavy ions and protons during irradiation in space, the small doses received during space travel could potentially have substantial carcinogenic risk. Clearly more investigation of the effects of heavy ions and protons is needed before accurate risk assessment for prolonged travel in space can be done. One means to mitigate the increased risk of cancer due to radiation exposure in space is by developing effective countermeasures that can reduce the incidence of tumor development. Tamoxifen has recently been shown to be an effective chemopreventive agent in both animal models and humans for the prevention of mammary tumors. Tamoxifen is a unique drug, with a highly specific mechanism of action affecting a specific radiation-sensitive population of epithelial cells in the mammary gland. In human studies, the annual incidence of a primary tumor in the contralateral breast of women with previous breast cancer is about 8 per 1000, making them an exceedingly high-risk group for the development of breast cancer. In this high risk group, treated with tamoxifen, daily, for 2 years, the incidence of a new primary tumor in the contralateral breast was approximately one third of that noted in the non-tamoxifen treatment group. Tamoxifen antagonizes the action of estrogen by competing for the nuclear receptor complex thereby altering the association of the receptor complex and nuclear binding sites. Its effects in reducing the development of breast cancer could be accomplished by controlling clinically undetectable

  18. Swift heavy ion induced phase transformation and thermoluminescence properties of zirconium oxide

    NASA Astrophysics Data System (ADS)

    Lokesha, H. S.; Nagabhushana, K. R.; Singh, Fouran

    2016-07-01

    Zirconium oxide (ZrO2) powder is synthesized by combustion technique. XRD pattern of ZrO2 shows monoclinic phase with average crystallite size 35 nm. Pellets of ZrO2 are irradiated with 100 MeV swift Si7+, Ni7+ and 120 MeV swift Ag9+ ions in the fluence range 3 × 1010-3 × 1013 ions cm-2. XRD pattern show the main diffraction peak correspond to monoclinic and tetragonal phase of ZrO2 in 2θ range 27-33°. Structural phase transformation is observed for Ni7+ and Ag9+ ion irradiated samples at a fluence 1 × 1013 ions cm-2 and 3 × 1012 ions cm-2 respectively, since the deposited electronic energy loss exceeds an effective threshold (>12 keV nm-1). Phase transition induced by Ag9+ ion is nearly 2.9 times faster than Ni7+ ion at 1 × 1013 ions cm-2. Ag9+ ion irradiation leads two ion impact processes. Thermoluminescence (TL) glow curves exhibit two glows, a well resolved peak at ∼424 K and unresolved peak at 550 K for all SHI irradiated samples. TL response is decreased with increase of ion fluence. Beyond 3 × 1012 ions cm-2, samples don't exhibit TL due to annihilation of defects.

  19. Heavy ion induced Single Event Phenomena (SEP) data for semiconductor devices from engineering testing

    NASA Technical Reports Server (NTRS)

    Nichols, Donald K.; Huebner, Mark A.; Price, William E.; Smith, L. S.; Coss, James R.

    1988-01-01

    The accumulation of JPL data on Single Event Phenomena (SEP), from 1979 to August 1986, is presented in full report format. It is expected that every two years a supplement report will be issued for the follow-on period. This data for 135 devices expands on the abbreviated test data presented as part of Refs. (1) and (3) by including figures of Single Event Upset (SEU) cross sections as a function of beam Linear Energy Transfer (LET) when available. It also includes some of the data complied in the JPL computer in RADATA and the SPACERAD data bank. This volume encompasses bipolar and MOS (CMOS and MHNOS) device data as two broad categories for both upsets (bit-flips) and latchup. It also includes comments on less well known phenomena, such as transient upsets and permanent damage modes.

  20. Analysis of Heavy Ion-Induced Chromosome Aberrations in Human Fibroblast Cells Using In Situ Hybridization

    NASA Technical Reports Server (NTRS)

    Wu, Honglu; Durante, Marco; Furusawa, Yoshiya; George, Kerry; Kawata, Tetsuya; Cucinotta, Francis A.

    2003-01-01

    Confluent human fibroblast cells (AG1522) were irradiated with gamma rays, 490 MeV/nucleon Si, or with Fe ions at either 200 or 500 MeV/nucleon. The cells were allowed to repair at 37 0 C for 24 hours after exposure, and a chemically induced premature chromosome condensation (PCC) technique was used to condense chromosomes in the G2 phase of the cell cycle. Unrejoined chromosomal breaks and complex exchanges were analyzed in the irradiated samples. In order to verify that chromosomal breaks were truly unrejoined, chromosome aberrations were analyzed using a combination of whole chromosome specific probes and probes specific for the telomere region of the chromosome. Results showed that the frequency of unrejoined chromosome breaks was higher after high-LET radiation, and consequently, the ratio of incomplete to complete exchanges increased steadily with LET up to 440 keV/micron, the highest LET value in the present study. For samples exposed to 200 MeV/nucleon Fe ions, chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique that allows identification of both complex and truly incomplete exchanges. Results of the mFISH study showed that 0.7 and 3 Gy dose of the Fe ions produced similar ratios of complex to simple exchanges and incomplete to complete exchanges, values for which were higher than those obtained after a 6 Gy gamma exposure. After 0.7 Gy of Fe ions, most complex aberrations were found to involve three or four chromosomes, indicating the maximum number of chromosome domains traversed by a single Fe ion track. 2

  1. Observation of Heavy-Ion-Induced Wake-Potential Interference Effects

    NASA Astrophysics Data System (ADS)

    Frischkorn, H. J.; Groeneveld, K. O.; Koschar, P.; Latz, R.; Schader, J.

    1982-11-01

    The superposition of the wake potentials of Coulomb-exploding fragments of diatomic molecular projectiles penetrating a solid cause potential oscillations at the surface. The total electron yield per projectile serves as a signal to detect these oscillations. The plasma frequency of the solid and the wake-potential wavelength can be deduced from the data.

  2. Capture and Fusion-Fission Processes in Heavy Ion Induced Reactions

    NASA Astrophysics Data System (ADS)

    Itkis, M. G.; Beghini, S.; Behera, B. R.; Bogatchev, A. A.; Bouchat, V.; Corradi, L.; Dorvaux, O.; Fioretto, E.; Gadea, A.; Hanappe, F.; Itkis, I. M.; Jandel, M.; Kliman, J.; Knyazheva, G. N.; Kondratiev, N. A.; Kozulin, E. M.; Krupa, L.; Latina, A.; Lyapin, V. G.; Materna, T.; Montagnoli, G.; Oganessian, Yu. Ts.; Pokrovsky, I. V.; Prokhorova, E. V.; Rowley, N.; Rubchenya, V. A.; Rusanov, A. Ya.; Sagaidak, R. N.; Scarlassara, F.; Schmitt, C.; Stefanini, A. M.; Stuttge, L.; Szilner, S.; Trotta, M.; Trzaska, W. H.; Voskresenski, V. M.

    2005-11-01

    Results of the experiments aimed at the study of fission and quasi-fission processes in the reactions 12C+204Pb, 48Ca+144,154Sm, 168Er, 208Pb, 238U, 244Pu, 248Cm; 58Fe+208Pb, 244Pu, 248Cm, and 64Ni+186W, 242Pu are presented. The choice of the above-mentioned reactions was inspired by the experiments on the production of the isotopes 283112, 289114 and 283116 at Dubna using the same reactions. The 58Fe and 64Ni projectiles were chosen since the corresponding projectile-target combinations lead to the synthesis of even heavier elements. The experiments were carried out at the U-400 accelerator of the Flerov Laboratory of Nuclear Reactions (JINR, Russia), the XTU Tandem accelerator of the National Laboratory of Legnaro (LNL, Italy) and the Accelerator of the Laboratory of University of Jyvaskyla (JYFL, Finland) using the time-of-flight spectrometer of fission fragments CORSET and the neutron multi-detector DEMON. The role of shell effects and the influence of the entrance channel asymmetry and the deformations of colliding nucleus on the mechanism of the fusion-fission and the competitive process of quasi-fission are discussed.

  3. Heavy ion induced damage to plasmid DNA: plateau region vs. spread out Bragg-peak

    NASA Astrophysics Data System (ADS)

    Dang, H. M.; van Goethem, M. J.; van der Graaf, E. R.; Brandenburg, S.; Hoekstra, R.; Schlathölter, T.

    2011-08-01

    We have investigated the damage of synthetic plasmid pBR322 DNA in dilute aqueous solutions induced by fast carbon ions. The relative contribution of indirect damage and direct damage to the DNA itself is expected to vary with linear energy transfer along the ion track, with the direct damage contribution increasing towards the Bragg peak. Therefore, 12C ions at the spread-out Bragg peak (dose averaged LET∞ = 189 ± 15 keV/ μm) and in the plateau region of the Bragg curve (LET = 40 keV/ μm) were employed and the radical scavenger concentration in the plasmid solution was varied to quantify the indirect effect. In order to minimize the influence of 12C break-up fragments, a relatively low initial energy of 90 MeV/nucleon was employed for the carbon ions. DNA damage has been quantified by subsequent electrophoresis on agarose gels. We find that strand breaks due to both indirect and direct effects are systematically higher in the plateau region as compared to the Bragg peak region with the difference being smallest at high scavenging capacities. In view of the fact that the relative biological effectiveness for many biological endpoints is maximum at the Bragg peak our findings imply that DNA damage at the Bragg peak is qualitatively most severe.

  4. Wwox inactivation enhances mammary tumorigenesis.

    PubMed

    Abdeen, S K; Salah, Z; Maly, B; Smith, Y; Tufail, R; Abu-Odeh, M; Zanesi, N; Croce, C M; Nawaz, Z; Aqeilan, R I

    2011-09-08

    Breast cancer is the leading cause of cancer-related death in women worldwide. Expression of the WWOX tumor suppressor is absent or reduced in a large proportion of breast tumors suggesting that loss of WWOX may contribute to breast tumorigenesis. Wwox-deficient mice die by 3-4 weeks of age precluding adult tumor analysis. To evaluate the effect of WWOX-altered expression on mammary tumor formation, the Wwox-heterozygous allele was back crossed onto the C3H mammary tumor-susceptible genetic background (Wwox(C3H)+/-) and incidence of mammary tumor formation was evaluated. Although 50% of the female Wwox(C3H)+/- mice developed mammary carcinomas, only 7% of Wwox(C3H)+/+ mice did. Intriguingly, mammary tumors in Wwox(C3H)+/- mice frequently lost WWOX protein expression suggesting a genetic predisposition toward mammary tumorigenesis. Immunohistochemical staining of hormone receptors revealed loss of estrogen receptor-α (ER) and progesterone receptor in the majority of these tumors. In vitro, depletion of WWOX in MCF7 ER-positive cells led to reduced ER expression and reduced sensitivity to tamoxifen and estrogen treatment and was associated with enhanced survival and anchorage-independent growth. Finally, cDNA array analyses of murine normal mammary epithelial cells and mammary tumors identified 163 significantly downreguated and 129 upregulated genes in the tumors. The majority of differentially expressed genes were part of pathways involved in cellular movement, cell-to-cell signaling and interaction, cellular development, cellular growth and proliferation and cell death. These changes in gene expression of mouse mammary tumors in Wwox(C3H)+/- mice resemble, at least in part, human breast cancer development. Our findings demonstrate the critical role that the WWOX tumor suppressor gene has in preventing tumorigenesis in breast cancer.

  5. /sup 20/neon ion- and x-ray-induced mammary carcinogenesis in female rats

    SciTech Connect

    Shellabarger, C.J.; Baum, J.W.; Holtzman, S.; Stone, J.P.

    1983-01-01

    One of the proposed uses of heavy ion irradiation is to image lesions of the human female breast. The rat model system was chosen to assess the carcinogenic potential of heavy ion irradiation in the belief that data obtained from rat studies would have a qualitatively predictive value for the human female. Accordingly, female rats were exposed to /sup 20/Ne ions at the BEVALAC and studied for the development of mammary neoplasia for 312 +- 2 days at Brookhaven along with rats exposed concurrently to x-irradiation or to no irradiation. As the dose of either type of radiation was increased the percent of rats with mammary adenocarcinomas, and the percent of rats with mammary fibroadenomas, tended to increase. At a prevalence of 20%, the RBE for /sup 20/Neon ions for mammary adenocarcinomas was estimated to be larger than 5 and for mammary fibroadenomas the RBE was estimated to be less than 2. No conclusion was reached concerning whether or not the RBE might vary with dose. We suggest that /sup 20/Ne ions do have a carcinogenic potential for rat mammary tissue and that this carcinogenic potential is likely to be greater than for x-irradiation. (DT)

  6. Experimental mammary carcinogenesis - Rat models.

    PubMed

    Alvarado, Antonieta; Faustino-Rocha, Ana I; Colaço, Bruno; Oliveira, Paula A

    2017-03-15

    Mammary cancer is one of the most common cancers, victimizing more than half a million of women worldwide every year. Despite all the studies in this field, the current therapeutic approaches are not effective and have several devastating effects for patients. In this way, the need to better understand the mammary cancer biopathology and find effective therapies led to the development of several rodent models over years. With this review, the authors intended to provide the readers with an overview of the rat models used to study mammary carcinogenesis, with a special emphasis on chemically-induced models.

  7. Characterization of ion-induced radiation effects in nuclear materials using synchrotron x-ray techniques

    DOE PAGES

    Lang, Maik; Tracy, Cameron L.; Palomares, Raul I.; ...

    2015-05-01

    Recent efforts to characterize the nanoscale structural and chemical modifications induced by energetic ion irradiation in nuclear materials have greatly benefited from the application of synchrotron-based x-ray diffraction (XRD) and x-ray absorption spectroscopy (XAS) techniques. Key to the study of actinide-bearing materials has been the use of small sample volumes, which are particularly advantageous, as the small quantities minimize the level of radiation exposure at the ion-beam and synchrotron user facility. This approach utilizes energetic heavy ions (energy range: 100 MeV–3 GeV) that pass completely through the sample thickness and deposit an almost constant energy per unit length along theirmore » trajectory. High energy x-rays (25–65 keV) from intense synchrotron light sources are then used in transmission geometry to analyze ion-induced structural and chemical modifications throughout the ion tracks. We describe in detail the experimental approach for utilizing synchrotron radiation (SR) to study the radiation response of a range of nuclear materials (e.g., ThO2 and Gd2TixZr2–xO7). Also addressed is the use of high-pressure techniques, such as the heatable diamond anvil cell, as a new means to expose irradiated materials to well-controlled high-temperature (up to 1000 °C) and/or high-pressure (up to 50 GPa) conditions. Furthermore, this is particularly useful for characterizing the annealing kinetics of irradiation-induced material modifications.« less

  8. Characterization of ion-induced radiation effects in nuclear materials using synchrotron x-ray techniques

    SciTech Connect

    Lang, Maik; Tracy, Cameron L.; Palomares, Raul I.; Zhang, Fuxiang; Severin, Daniel; Bender, Markus; Trautmann, Christina; Park, Changyong; Prakapenka, Vitali B.; Skuratov, Vladimir A.; Ewing, Rodney C.

    2015-05-01

    Recent efforts to characterize the nanoscale structural and chemical modifications induced by energetic ion irradiation in nuclear materials have greatly benefited from the application of synchrotron-based x-ray diffraction (XRD) and x-ray absorption spectroscopy (XAS) techniques. Key to the study of actinide-bearing materials has been the use of small sample volumes, which are particularly advantageous, as the small quantities minimize the level of radiation exposure at the ion-beam and synchrotron user facility. This approach utilizes energetic heavy ions (energy range: 100 MeV–3 GeV) that pass completely through the sample thickness and deposit an almost constant energy per unit length along their trajectory. High energy x-rays (25–65 keV) from intense synchrotron light sources are then used in transmission geometry to analyze ion-induced structural and chemical modifications throughout the ion tracks. We describe in detail the experimental approach for utilizing synchrotron radiation (SR) to study the radiation response of a range of nuclear materials (e.g., ThO2 and Gd2TixZr2–xO7). Also addressed is the use of high-pressure techniques, such as the heatable diamond anvil cell, as a new means to expose irradiated materials to well-controlled high-temperature (up to 1000 °C) and/or high-pressure (up to 50 GPa) conditions. Furthermore, this is particularly useful for characterizing the annealing kinetics of irradiation-induced material modifications.

  9. Plasma-ion-induced Sputtering And Heating Of Titan'S Atmosphere

    NASA Astrophysics Data System (ADS)

    Tucker, Orenthal J.

    2006-09-01

    Plasma-ion-induced sputtering and heating of Titan's atmosphere O.J. Tucker (1), R.E. Johnson (1), M. Michael (1), V.I. Shematovich (1,2) J.H. Luhmann (3), S.A. Ledvina (3) (1) University of Virginia, Charlottesville, VA 22904, USA (2) Institute of Astronomy RAS, Moscow 109017, Russia, (3) University of California, Berkeley, CA 94720, USA Titan is unique among the outer solar system icy satellites in having an atmosphere with a column density about ten times that of the Earth's atmosphere. Atmospheres equivalent in size similar to that at Titan would have been removed from the icy Galilean satellites by the plasma trapped in the Jovian magnetosphere (Johnson 2004). In this paper we describe the deposition of energy, the erosion and the expansion of the upper atmosphere of Titan using Direct Simulation Monte Carlo models (Shematovich et al. 2003; Michael et al. 2005). These calculations are used to calibrate semi-empirical models of atmospheric sputtering (Johnson 1994) that can be employed in interpreting Cassini data at Titan. It is shown that the globally averaged flux of magnetospheric and pickup ions deposit more energy in Titan's upper atmosphere than solar radiation. Using a number of plasma conditions, the temperature and density vs. altitude above the exobase and the rate of escape are calculated and compared to available Cassini data. References: Johnson, R.E. "Plasma-induced Sputtering of an Atmosphere" in Space Science Reviews 69 215-253 (1994). Johnson. R.E., “ The magnetospheric plasma-driven evolution of satellite atmospheres” Astrophys. J. 609, L99-L102 (2004). Michael M., R.E. Johnson, F. Leblanc, M. Liu, J.G. Luhmann, and V.I. Shematovich, "Ejection of nitrogen from Titan's atmosphere by magnetospheric ions and pick-up ions", Icarus 175, 263-267 (2005). Shematovich, V.I., R.E. Johnson, M. Michael, and J.G. Luhmann,"Nitrogen loss from Titan", JGR 108, No. E8, 5087, doi:10.1029/2003JE002094 (2003). 1

  10. Mammary Analogue Secretory Carcinoma.

    PubMed

    Stevens, Todd M; Parekh, Vishwas

    2016-09-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement as secretory carcinoma of the breast. Prior to its recognition, MASC cases were commonly labeled acinic cell carcinoma and adenocarcinoma, not otherwise specified. Despite distinctive histologic features, MASC may be difficult to distinguish from other salivary gland tumors, in particular zymogen-poor acinic cell carcinoma and low-grade salivary duct carcinoma. Although characteristic morphologic and immunohistochemical features form the basis of a diagnosis of MASC, the presence of an ETV6-NTRK3 gene fusion is confirmatory. Given its recent recognition the true prognostic import of MASC is not yet clearly defined.

  11. Cloning of Mammary Stem Cells

    DTIC Science & Technology

    2001-11-01

    these parity-induced cells do represent a totipotent mammary stem cell population per se, but these cells might support stem cell maintenance as... Stem Cells PRINCIPAL INVESTIGATOR: Dr. Kay-Uwe Wagner CONTRACTING ORGANIZATION: University of Nebraska Medical Center Omaha, Nebraska 68198-6810 REPORT...Mammary Stem Cells DAMD17-00-1-0641 6. AUTHOR(S) Dr. Kay-Uwe Wagner 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT

  12. Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment

    PubMed Central

    2011-01-01

    Introduction The mammary primordium forms during embryogenesis as a result of inductive interactions between its constitutive tissues, the mesenchyme and epithelium, and represents the earliest evidence of commitment to the mammary lineage. Previous studies of embryonic mouse mammary epithelium indicated that, by mid-gestation, these cells are determined to a mammary cell fate and that a stem cell population has been delimited. Mammary mesenchyme can induce mammary development from simple epithelium even across species and classes, and can partially restore features of differentiated tissue to mouse mammary tumours in co-culture experiments. Despite these exciting properties, the molecular identity of embryonic mammary cells remains to be fully characterised. Methods Here, we define the transcriptome of the mammary primordium and the two distinct cellular compartments that comprise it, the mammary primordial bud epithelium and mammary mesenchyme. Pathway and network analysis was performed and comparisons of embryonic mammary gene expression profiles to those of both postnatal mouse and human mammary epithelial cell sub-populations and stroma were made. Results Several of the genes we have detected in our embryonic mammary cell signatures were previously shown to regulate mammary cell fate and development, but we also identified a large number of novel candidates. Additionally, we determined genes that were expressed by both embryonic and postnatal mammary cells, which represent candidate regulators of mammary cell fate, differentiation and progenitor cell function that could signal from mammary lineage inception during embryogenesis through postnatal development. Comparison of embryonic mammary cell signatures with those of human breast cells identified potential regulators of mammary progenitor cell functions conserved across species. Conclusions These results provide new insights into genetic regulatory mechanisms of mammary development, particularly

  13. Initiation of oncogenic transformation in human mammary epithelial cells by charged particles

    NASA Technical Reports Server (NTRS)

    Yang, T. C.; Georgy, K. A.; Craise, L. M.; Durante, M.

    1997-01-01

    Experimental studies have shown that high linear-energy transfer (LET) charged particles can be more effective than x-rays and gamma-rays in inducing oncogenic transformation in cultured cells and tumors in animals. Based on these results, experiments were designed and performed with an immortal human mammary epithelial cell line (H184B5), and several clones transformed by heavy ions were obtained. Cell fusion experiments were subsequently done, and results indicate that the transforming gene(s) is recessive. Chromosome analysis with fluorescence in situ hybridization (FISH) techniques also showed additional translocations in transformed human mammary epithelial cells. In addition, studies with these cell lines indicate that heavy ions can effectively induce deletion, break, and dicentrics. Deletion of tumor suppressor gene(s) and/or formation of translocation through DNA double strand breaks is a likely mechanism for the initiation of oncogenic transformation in human mammary epithelial cells.

  14. Initiation of oncogenic transformation in human mammary epithelial cells by charged particles

    NASA Technical Reports Server (NTRS)

    Yang, T. C.; Georgy, K. A.; Craise, L. M.; Durante, M.

    1997-01-01

    Experimental studies have shown that high linear-energy transfer (LET) charged particles can be more effective than x-rays and gamma-rays in inducing oncogenic transformation in cultured cells and tumors in animals. Based on these results, experiments were designed and performed with an immortal human mammary epithelial cell line (H184B5), and several clones transformed by heavy ions were obtained. Cell fusion experiments were subsequently done, and results indicate that the transforming gene(s) is recessive. Chromosome analysis with fluorescence in situ hybridization (FISH) techniques also showed additional translocations in transformed human mammary epithelial cells. In addition, studies with these cell lines indicate that heavy ions can effectively induce deletion, break, and dicentrics. Deletion of tumor suppressor gene(s) and/or formation of translocation through DNA double strand breaks is a likely mechanism for the initiation of oncogenic transformation in human mammary epithelial cells.

  15. Insulin receptors in the mammary gland

    SciTech Connect

    Smith, D.H.

    1986-01-01

    Insulin binding studies were conducted using mammary membrane preparations to further the authors understanding of insulin's role in regulating mammary metabolism, particularly ruminant mammary metabolism. Specific objectives were to: (1) characterize insulin binding to bovine mammary microsomes and determine if the specificity and kinetics of binding indicate the presence of insulin receptors in bovine mammary gland; (2) examine and compare insulin binding by liver and mammary microsomes of the pig and dairy cow; (3) examine insulin binding to bovine milk fat globule membranes (MFGM) and evaluate this model's usefulness in assessing insulin receptor regulation in the mammary gland of the cow; (4) examine the effect of dietary fat in insulin binding by rat mammary and liver microsomes. The specificity and kinetics of /sup 125/I-insulin binding of bovine mammary microsomes indicated the presence of insulin receptors in bovine mammary gland. Bovine liver and mammary microsomes specifically bound less /sup 125/I-insulin than did the corresponding porcine microsomes, and mammary microsomes, regardless of species, specifically bound less /sup 125/I-insulin than did liver microsomes. These differences in binding suggest differences in insulin responsiveness between pigs and cattle, as well as between the liver and mammary glands.

  16. Heavy ion collisions and the pre-equilibrium exciton model

    SciTech Connect

    Betak, E.

    2012-10-20

    We present a feasible way to apply the pre-equilibrium exciton model in its masterequation formulation to heavy-ion induced reactions including spin variables. Emission of nucleons, {gamma}'s and also light clusters is included in our model.

  17. Mammary Cancer and Activation of Transposable Elements

    DTIC Science & Technology

    2014-09-01

    AD_________________ Award Number: W81XWH-11-1-0402 TITLE: Mammary Cancer and Activation...TYPE Annual 3. DATES COVERED 1 Sep 2013 – 31 Aug 2014 4. TITLE AND SUBTITLE Mammary Cancer and Activation of Transposable Elements 5a. CONTRACT...investigate molecular events occurring in the preclinical stages of mammary cancer. Specifically, the project investigates the intersection between the

  18. FACS Sorting Mammary Stem Cells.

    PubMed

    Iriondo, Oihana; Rábano, Miriam; Vivanco, María D M

    2015-01-01

    Fluorescent-activated cell sorting (FACS) represents one of the key techniques that have been used to isolate and characterize stem cells, including cells from the mammary gland. A combination of approaches, including recognition of cell surface antigens and different cellular activities, has facilitated the identification of stem cells from the healthy mammary gland and from breast tumors. In this chapter we describe the protocol to use FACS to separate breast cancer stem cells, but most of the general principles discussed could be applied to sort other types of cells.

  19. Preface: Photon and fast Ion induced Processes in Atoms, MOlecules and Nanostructures (PIPAMON)

    NASA Astrophysics Data System (ADS)

    Kövér, László

    2016-02-01

    This Special Issue contains selected papers of contributions presented in the International Workshop on Photon and fast Ion induced Processes in Atoms, MOlecules and Nanostructures (PIPAMON), held between March 24 and 26, 2015 in Debrecen, Hungary. The venue, the Aquaticum Thermal and Wellness Hotel provided a pleasant ;all-under-one-roof; environment for the event.

  20. Simultaneous measurement of the average ion-induced electron emission yield and the mean charge for isotachic ions in carbon foils

    NASA Astrophysics Data System (ADS)

    Arrale, A. M.; Zhao, Z. Y.; Kirchhoff, J. F.; Weathers, D. L.; McDaniel, F. D.; Matteson, S.

    1997-02-01

    Knowledge of the incident ion's atomic number (Z1) dependence of ion-induced electron emission yields can be the basis for a general understanding of ion-atom interaction phenomena and, in particular, for the design of Z1-sensitive detectors that could be useful, for example, in the separation of isobars in accelerator mass spectrometry. The Z1 dependence of ion-induced electron emission yields, γ, has been investigated using heavy ions C3+, O3+, F+3, Na3+, Al3+, Si3+, P3+, S3+, Cl3+, K3+, Ti3+, Cr3+, Mn4+, Fe4+, Co4+, Ni4+, Cu4+, Ga4+, As5+, Br5+, Ru7+, Ag7+, Sn7+, and I8+ of identical velocity (v=2v0, where v0 is the Bohr velocity) normally incident on 50 μg/cm2 sputter-cleaned carbon foils. Measured yields as a function of Z1 reveal an oscillatory behavior with pronounced maxima and minima. Contrary to previously reported yields that assumed a monotonically increasing empirical mean charge state for the exiting ion, the present work indicates the Z1 oscillations in the experimentally measured yields, a fact masked in previous work. The strong Z1 oscillations can only be observed by simultaneous measurement of the yield and the mean charge state.

  1. In situ investigation of ion-induced dewetting of a thin iron-oxide film on silicon by high resolution scanning electron microscopy

    SciTech Connect

    Amirthapandian, S.; Schuchart, F.; Garmatter, D.; Bolse, W.

    2012-11-15

    Using our new in situ high resolution scanning electron microscope, which is integrated into the UNILAC ion beamline at the Helmholtzzentrum fuer Schwerionenforschung (GSI) in Darmstadt, Germany, we investigated the swift heavy ion induced dewetting of a thin iron oxide layer on Si. Besides heterogeneous hole nucleation at defects and spontaneous (homogeneous) hole nucleation, we could clearly identify a dewetting mechanism, which is similar to the spinodal dewetting observed for liquid films. Instead of being due to capillary waves, it is based on a stress induced surface instability. The latter results in the formation of a wavy surface with constant dominant wave-length and increasing amplitude during ion irradiation. Dewetting sets in as soon as the wave-troughs reach the film-substrate interface. Inspection of the hole radii and rim shapes indicates that removal of the material from the hole area occurs mainly by plastic deformation at the inner boundary and ion induced viscous flow in the peripheral zone due to surface tension.

  2. Prevention of Human Mammary Carcinogenesis

    DTIC Science & Technology

    1995-06-30

    selected naturally-occurring agents (-)-epigallocatechin gallate ( EGCG ), indole-3-carbinol (13C) and genistein (GEN) for growth inhibition of 184-B5...mechanisms of BP-induced and GEN-induced alterations in cell cycle are being investigated in the ongoing studies. In addition, effects of 13C and EGCG are...rodent mammary tumorigenesis. The maximally nontoxic doses of EGCG , 13C and GEN identified by initial dose-response experiments, were used. The data

  3. Ectopic mammary tissue in vulva.

    PubMed

    Dordević, Momcilo; Jovanović, Bozidar; Mitrović, Slobodanka; Dordević, Gordana

    2008-05-01

    Ectopic mammary gland tissue is a residual tissue that persists during the embryologic development along ectodermal primitive milk streaks. Incomplete involution anywhere along the primitive milk streak can result in accessory or ectopic mammary tissue. A woman, 27-year old, admitted to Obstetrics and Gynecology Clinic Kragujevac for surgery, of goose-egg size, vulva tumor, of elastic consistency. Menarche started in 12 years of age, with the regular menstrual cycle, without previous gyneocological diseases. The woman had one pregnancy terminated by cesarean section because of the multiple (twin) pregnancy. Excision of the tumor was completely done in the total endotracheal anesthesia. Pathohistologic (PH) findings was: Dysplasia fibrosa cystica simplex mammae, with focuses of sclerosing adenosis. Expression of estrogen (ER) and progesterone receptors (PR) were positive. Ectopic mammary tissue in vulva in adult period is very rarely seen, and can be changed pathologically as well as normally positioned breast tissue into benign cystic changes, benign tumors, adenomas and fibroadenomas and tumors. Cells with low ER/PR receptor level grow independently of estrogene stimulation and they could be resistant to hormonal therapy effects.

  4. Modified growth kinetics of ion induced yttrium--silicide layers during subsequent thermal annealing

    SciTech Connect

    Alford, T.L.; Mayer, J.W. )

    1991-12-02

    Yttrium and amorphous silicon bilayers were irradiated with 600-keV inert ions between {minus}190 and 265 {degree}C. Ion-induced YSi{sub 1.7} layers occurred in those samples irradiated above {ge} (R18)205 {degree}C. These ion-mixed samples were thermally annealed at temperatures between 325 and 380 {degree}C. The diffusion-limited growth was observed only in those samples which had an ion-induced YSi{sub 1.7} layer present prior to thermal annealing. This type of growth is distinctly different from the interface limited, nonuniform, and irreproducible growth seen during typical thermal annealing of yttrium and silicon bilayers. This type of growth still occurred in those samples annealed after ion irradiations at {le}190 {degree}C.

  5. Beam Energy Scaling on Ion-Induced Electron Yield from K+ Impacton Stainless Steel

    SciTech Connect

    Kireeff Covo, Michel; Molvik, Arthur; Friedman, Alex; Westenskow,Glen; Barnard, John J.; Cohen, Ronald; Grote, David; Lund, Steven M.; Seidl, Peter; Kwan, Joe W.; Logan, Grant; Baca, David; Bieniosek, Frank; Celata, Christine M.; Vay Jean-Luc; Vujic, Jasmina L.

    2006-01-01

    Electron clouds limit the performance of many major accelerators. Significant quantities of electrons result when halo ions are lost to beam tubes, generating gas which can be ionized and ion-induced electrons that can multiply and accumulate, causing degradation or loss of the ion beam. In order to understand the physical mechanisms of ion-induced electron production, experiments studied the impact of 50 to 400 keV K{sup +} ions on stainless steel surfaces near grazing incidence, using the 500 kilovolts Ion Source Test Stand (STS-500) at LLNL. The experimental electron yield scales with the electronic component (dE{sub e}/dx) of the stopping power. A theoretical model is developed, using TRIM code to evaluate dE{sub e}/dx at several depths in the target, to estimate the electron yield, which is compared with the experimental results.

  6. Energy dependence of ion-induced sputtering yields from monatomic solids at normal incidence

    SciTech Connect

    Yamamura, Y.; Tawara, H.

    1996-03-01

    The ion-induced sputtering yields from monatomic solids at normal incidence are presented graphically for various ion-target combinations as a function of the incident ion energy. To supplement the experimental data, sputtering yields are calculated by the Monte Carlo simulation code ACAT for some ion-target combinations. Each graph shows the available experimental and ACAT data points, together with the sputtering yields calculated by an empirical formula whose parameters determined from the best fit to available data.

  7. 9 CFR 310.17 - Inspection of mammary glands.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Inspection of mammary glands. 310.17... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.17 Inspection of mammary glands. (a) Lactating mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed...

  8. 9 CFR 310.17 - Inspection of mammary glands.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Inspection of mammary glands. 310.17... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.17 Inspection of mammary glands. (a) Lactating mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed...

  9. 9 CFR 310.17 - Inspection of mammary glands.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Inspection of mammary glands. 310.17... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.17 Inspection of mammary glands. (a) Lactating mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed...

  10. 9 CFR 310.17 - Inspection of mammary glands.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Inspection of mammary glands. 310.17... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.17 Inspection of mammary glands. (a) Lactating mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed...

  11. 9 CFR 310.17 - Inspection of mammary glands.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Inspection of mammary glands. 310.17... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.17 Inspection of mammary glands. (a) Lactating mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed...

  12. Transplantation of a mammary stromal cell line into a mammary fat pad: development of the site-specific in vivo analysis system for mammary stromal cells.

    PubMed

    Nakatani, Hajime; Aoki, Naohito; Nadano, Daita; Matsuda, Tsukasa

    2011-01-01

    The interaction between mammary epithelial and stromal tissue is considered to be important in breast tissue development. In this study, we developed a transplantation procedure for the mammary stromal fibroblastic cell line (MSF) to examine its life in vivo. First we established MSF cells which stably expressed lacZ (lacZ/MSF) and had characteristics of mammary stromal cells. The lacZ/MSF cells were then transplanted into a cleared mammary fat pad of syngenic mice with and without mammary primary epithelial organoids. Whole mount X-gal and carmine staining of the transplants revealed that a number of undifferentiated lacZ/MSF cells survived around the mammary epithelial tissue when transplanted with organoids. These results indicate that transplantation of MSF cells into mammary fat pad was accomplished by co-transplantation with primary mammary organoids. Finally, we discuss the application of transplantation procedure for in vivo studies of the mammary stromal tissue development and stromal-epithelial interactions.

  13. Mammary Malignancy in The Male

    PubMed Central

    Alexander, Leslie L.; Benninghoff, David L.; Camiel, Mortimer R.; Medina, Antonio

    1978-01-01

    Mammary carcinoma in the male, a relatively uncommon disease, represents about 0.9 to 1.5 percent of all breast cancers. 1,2 The authors reviewed 16 cases of male breast cancer seen in a 30-year period at the State University of New York, Kings County Hospital Medical Center in Brooklyn, and the North Shore University Hospital in Manhasset. Epidemiology, etiology, demography, signs and symptoms, management, and prognosis are discussed. A review of pertinent literature is presented. ImagesFigure 1Figure 2 PMID:722829

  14. Expression and significance of PTEN in canine mammary gland tumours.

    PubMed

    Qiu, Changwei; Lin, Degui; Wang, Jinqiu; Wang, Lei

    2008-10-01

    To explore the expression and clinical importance of the anti-oncogene phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in canine mammary gland tumours, PTEN expression was compared in 50 cases of canine mammary tumour and four examples of normal mammary tissue using real-time quantitative PCR. PTEN expression was similar in benign mammary tumours and normal mammary tissues (P>0.05), but was lower in malignant tumours than in normal mammary tissues or benign mammary tumours (P<0.001). PTEN expression was also low in the lymph node metastases of malignant mammary tumours. The expression profile of PTEN in malignant mammary tumours compared to those without lymph node metastasis varied significantly. Low-level PETN expression might play an important role in carcinogenesis and the progression of canine mammary tumours, and PTEN protein detection might be useful in evaluating tumour development and prognosis.

  15. Proximity potential for heavy ion reactions on deformed nuclei

    SciTech Connect

    Baltz, A. J.; Bayman, B. F.

    1982-01-01

    The usual treatment of the deformed optical model for analysis of heavy ion induced inelastic scattering data involves a deformed (target) radius, a spherical (projectile) radius and a potential strength dependent on the surface separation along the line between the two centers. Several authors using various approaches have shown that this center line potential is geometrically inadequate especially for description of higher L deformation parameters probed in heavy ion induced inelastic scattering experiments. A quantitatively adequate form of the deformed proximity potential suitable for use with a coupled channels reaction code in the analysis of inelastic scattering data above the Coulomb barrier is described. A major objective is to be able to extract reliably higher deformed multipole moments from such data. The deformed potential calculated in the folding model will serve as a geometrically exact benchmark to evaluate the accuracy of the proximity potential prescriptions. (WHK)

  16. Mammary and extramammary Paget's disease*

    PubMed Central

    Lopes, Lauro Lourival; Lopes, Ione Maria Ribeiro Soares; Lopes, Lauro Rodolpho Soares; Enokihara, Milvia M. S. S.; Michalany, Alexandre Osores; Matsunaga, Nobuo

    2015-01-01

    Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen's disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget's disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent. PMID:25830993

  17. Mammary gland tumors in male dogs.

    PubMed

    Saba, Corey F; Rogers, Kenita S; Newman, Shelley J; Mauldin, Glenna E; Vail, David M

    2007-01-01

    Reports of mammary-gland tumors in male dogs are lacking. To describe the clinical characteristics of mammary-gland tumors in male dogs. Eight male dogs diagnosed with mammary-gland tumors. Retrospective study. Medical databases from 3 institutions were searched. Medical records were abstracted, and owners and referring veterinarians contacted for follow-up information. Tissues were reviewed for histologic type, and immunohistochemical staining for estrogen and progesterone receptors (ER, PR) was performed. Eight dogs with histologically confirmed mammary-gland tumors were included in this retrospective study. Median age at diagnosis was 11.5 years. Four dogs were sexually intact; 4 were neutered. All were purebred. Mammary-gland tumors were incidental findings in 7 of 8 dogs. All dogs were treated with only surgical excision. All but 1 dog had benign epithelial tumors. The dog with the malignant tumor was the only dog to develop possible local recurrence but de novo tumor development cannot be excluded. No dog had evidence of metastatic disease at diagnosis. Based on institutional population data, it was determined that female dogs are 62 times more likely to develop mammary-gland tumors than male dogs (P < .001). Estrogen-receptor expression was strong in the majority of tumors; progesterone-receptor expression, although present in all tumors, was less intense. CONCLUSIONS/CLINICAL IMPORTANCE: This study suggests that mammary-gland tumors in male dogs are rare, usually benign, and surgery alone can provide long-term control in most dogs.

  18. Experimental evaluation of the pressure and temperature dependence of ion-induced nucleation.

    PubMed

    Munir, Muhammad Miftahul; Suhendi, Asep; Ogi, Takashi; Iskandar, Ferry; Okuyama, Kikuo

    2010-09-28

    An experimental system for the study of ion-induced nucleation in a SO(2)/H(2)O/N(2) gas mixture was developed, employing a soft x-ray at different pressure and temperature levels. The difficulties associated with these experiments included the changes in physical properties of the gas mixture when temperature and pressure were varied. Changes in the relative humidity (RH) as a function of pressure and temperature also had a significant effect on the different behaviors of the mobility distributions of particles. In order to accomplish reliable measurement and minimize uncertainties, an integrated on-line control system was utilized. As the pressure decreased in a range of 500-980 hPa, the peak concentration of both ions and nanometer-sized particles decreased, which suggests that higher pressure tended to enhance the growth of particles nucleated by ion-induced nucleation. Moreover, the modal diameters of the measured particle size distributions showed a systematic shift to larger sizes with increasing pressure. However, in the temperature range of 5-20 °C, temperature increases had no significant effects on the mobility distribution of particles. The effects of residence time, RH (7%-70%), and SO(2) concentration (0.08-6.7 ppm) on ion-induced nucleation were also systematically investigated. The results show that the nucleation and growth were significantly dependent on the residence time, RH, and SO(2) concentration, which is in agreement with both a previous model and previous observations. This research will be inevitable for a better understanding of the role of ions in an atmospheric nucleation mechanism.

  19. Ion-induced Processing of Cosmic Silicates: A Possible Formation Pathway to GEMS

    NASA Astrophysics Data System (ADS)

    Jäger, C.; Sabri, T.; Wendler, E.; Henning, Th.

    2016-11-01

    Ion-induced processing of dust grains in the interstellar medium and in protoplanetary and planetary disks plays an important role in the entire dust cycle. We have studied the ion-induced processing of amorphous MgFeSiO4 and Mg2SiO4 grains by 10 and 20 keV protons and 90 keV Ar+ ions. The Ar+ ions were used to compare the significance of the light protons with that of heavier, but chemically inert projectiles. The bombardment was performed in a two-beam irradiation chamber for in situ ion-implantation at temperatures of 15 and 300 K and Rutherford Backscattering Spectroscopy to monitor the alteration of the silicate composition under ion irradiation. A depletion of oxygen from the silicate structure by selective sputtering of oxygen from the surface of the grains was observed in both samples. The silicate particles kept their amorphous structure, but the loss of oxygen caused the reduction of ferrous (Fe2+) ions and the formation of iron inclusions in the MgFeSiO4 grains. A few Si inclusions were produced in the iron-free magnesium silicate sample pointing to a much less efficient reduction of Si4+ and formation of metallic Si inclusions. Consequently, ion-induced processing of magnesium-iron silicates can produce grains that are very similar to the glassy grains with embedded metals and sulfides frequently observed in interplanetary dust particles and meteorites. The metallic iron inclusions are strong absorbers in the NIR range and therefore a ubiquitous requirement to increase the temperature of silicate dust grains in IR-dominated astrophysical environments such as circumstellar shells or protoplanetary disks.

  20. Radiogenic transformation of human mammary epithelial cells in vitro

    NASA Technical Reports Server (NTRS)

    Yang, T. C.; Georgy, K. A.; Tavakoli, A.; Craise, L. M.; Durante, M.

    1996-01-01

    Cancer induction by space radiations is a major concern for manned space exploration. Accurate assessment of radiation risk at low doses requires basic understanding of mechanism(s) of radiation carcinogenesis. For determining the oncogenic effects of ionizing radiation in human epithelial cells, we transformed a mammary epithelial cell line (185B5), which was immortalized by benzo(a)pyrene, with energetic heavy ions and obtained several transformed clones. These transformed cells showed growth properties on Matrigel similar to human mammary tumor cells. To better understand the mechanisms of radiogenic transformation of human cells, we systematically examined the alterations in chromosomes and cancer genes. Among 16 autosomes examined for translocations, by using fluorescence in situ hybridization (FISH) technique, chromosomes 3, 12, 13, 15, 16, and 18 appeared to be normal in transformed cells. Chromosomes 1, 4, 6, 8, and 17 in transformed cells, however, showed patterns different from those in nontransformed cells. Southern blot analyses indicated no detectable alterations in myc, ras, Rb, or p53 genes. Further studies of chromosome 17 by using in situ hybridization with unique sequence p53 gene probe and a centromere probe showed no loss of p53 gene in transformed cells. Experimental results from cell fusion studies indicated that the transforming gene(s) is recessive. The role of genomic instability and tumor suppressor gene(s) in radiogenic transformation of human breast cells remains to be identified.

  1. Radiogenic transformation of human mammary epithelial cells in vitro

    NASA Technical Reports Server (NTRS)

    Yang, T. C.; Georgy, K. A.; Tavakoli, A.; Craise, L. M.; Durante, M.

    1996-01-01

    Cancer induction by space radiations is a major concern for manned space exploration. Accurate assessment of radiation risk at low doses requires basic understanding of mechanism(s) of radiation carcinogenesis. For determining the oncogenic effects of ionizing radiation in human epithelial cells, we transformed a mammary epithelial cell line (185B5), which was immortalized by benzo(a)pyrene, with energetic heavy ions and obtained several transformed clones. These transformed cells showed growth properties on Matrigel similar to human mammary tumor cells. To better understand the mechanisms of radiogenic transformation of human cells, we systematically examined the alterations in chromosomes and cancer genes. Among 16 autosomes examined for translocations, by using fluorescence in situ hybridization (FISH) technique, chromosomes 3, 12, 13, 15, 16, and 18 appeared to be normal in transformed cells. Chromosomes 1, 4, 6, 8, and 17 in transformed cells, however, showed patterns different from those in nontransformed cells. Southern blot analyses indicated no detectable alterations in myc, ras, Rb, or p53 genes. Further studies of chromosome 17 by using in situ hybridization with unique sequence p53 gene probe and a centromere probe showed no loss of p53 gene in transformed cells. Experimental results from cell fusion studies indicated that the transforming gene(s) is recessive. The role of genomic instability and tumor suppressor gene(s) in radiogenic transformation of human breast cells remains to be identified.

  2. Mammary gland tumors in captive African hedgehogs.

    PubMed

    Raymond, J T; Gerner, M

    2000-04-01

    From December 1995 to July 1999, eight mammary gland tumors were diagnosed in eight adult captive female African hedgehogs (Atelerix albiventris). The tumors presented as single or multiple subcutaneous masses along the cranial or caudal abdomen that varied in size for each hedgehog. Histologically, seven of eight (88%) mammary gland tumors were malignant. Tumors were classified as solid (4 cases), tubular (2 cases), and papillary (2 cases). Seven tumors had infiltrated into the surrounding stroma and three tumors had histologic evidence of neoplastic vascular invasion. Three hedgehogs had concurrent neoplasms. These are believed to be the first reported cases of mammary gland tumors in African hedgehogs.

  3. Adenoma of anogenital mammary-like glands.

    PubMed

    Ahmed, Sartaj; Campbell, Ross M; Li, Jin Hong; Wang, Li Juan; Robinson-Bostom, Leslie

    2007-11-01

    Adenomas in the anogenital region are uncommon. There has been debate about the origin, including ectopic breast tissue, cutaneous apocrine gland, and most recently anogenital mammary-like gland. An anogenital mass in a 36-year-old woman was excised, and histopathologic examination and immunostaining were performed. Microscopic tissue sections showed a morphologic pattern similar to that of a mammary fibroadenoma, and immunostaining demonstrated the presence of estrogen receptors and progesterone receptors. The possibility of adenomas of anogenital mammary-like glands should be considered when evaluating patients with a mass in this area with confirmation by tissue biopsy or aspiration cytology.

  4. Ion-Induced Nanoscale Ripple Patterns on Si Surfaces: Theory and Experiment

    PubMed Central

    Keller, Adrian; Facsko, Stefan

    2010-01-01

    Nanopatterning of solid surfaces by low-energy ion bombardment has received considerable interest in recent years. This interest was partially motivated by promising applications of nanopatterned substrates in the production of functional surfaces. Especially nanoscale ripple patterns on Si surfaces have attracted attention both from a fundamental and an application related point of view. This paper summarizes the theoretical basics of ion-induced pattern formation and compares the predictions of various continuum models to experimental observations with special emphasis on the morphology development of Si surfaces during sub-keV ion sputtering. PMID:28883355

  5. Particle reflection and ion-induced desorption from tungsten surfaces with chemisorbed nitrogen

    NASA Astrophysics Data System (ADS)

    Yamamura, Y.; Kimura, H.

    1987-06-01

    Using the Monte Carlo simulation program ACAT, ion-induced desorption yields of nitrogen chemisorbed on tungsten surfaces and the associated particle reflection coefficients have been calculated for low-energy helium-ions. It is found that both the particle reflection coefficients and the energy distributions of the reflected particles depend strongly on the thickness of the adsorbate layer on the surface if the ion energy is in the threshold regime and that the collision sequence of the near-threshold mechanism includes at least two adsorbate atoms. The ACAT desorption yields are found to be in good agreement with experimental yields.

  6. Particle reflection and ion-induced desorption from tungsten surfaces with chemisorbed nitrogen

    NASA Astrophysics Data System (ADS)

    Yamamura, Y.; Kimura, H.

    Using the Monte Carlo simulation program ACAT, ion-induced desorption yields of nitrogen chemisorbed on tungsten surfaces and the associated particle reflection coefficients have been calculated for low-energy helium-ions. It is found that both the particle reflection coefficients and the energy distributions of the reflected particles depend strongly on the thickness of the adsorbate layer on the surface if the ion energy is in the threshold regime and that the collision sequence of the near-threshold mechanism includes at least two adsorbate atoms. The ACAT desorption yields are found to be in good agreement with experimental yields.

  7. Fission and quasifission modes in heavy-ion-induced reactions leading to the formation of Hs{sup *}

    SciTech Connect

    Itkis, I. M.; Kozulin, E. M.; Itkis, M. G.; Knyazheva, G. N.; Bogachev, A. A.; Chernysheva, E. V.; Krupa, L.; Oganessian, Yu. Ts.; Zagrebaev, V. I.; Rusanov, A. Ya.; Goennenwein, F.; Dorvaux, O.; Stuttge, L.; Hanappe, F.; Vardaci, E.; Goes Brennand, E. de

    2011-06-15

    Mass and energy distributions of binary reaction products obtained in the reactions {sup 22}Ne+{sup 249}Cf,{sup 26}Mg+{sup 248}Cm, {sup 36}S+{sup 238}U, and {sup 58}Fe+{sup 208}Pb have been measured. All reactions lead to Hs isotopes. At energies below the Coulomb barrier the bimodal fission of Hs{sup *}, formed in the reaction {sup 26}Mg+{sup 248}Cm, is observed. In the reaction {sup 36}S+{sup 238}U, leading to the formation of a similar compound nucleus, the main part of the symmetric fragments arises from the quasifission process. At energies above the Coulomb barrier fusion-fission is the main process leading to the formation of symmetric fragments for both reactions with Mg and S ions. In the case of the {sup 58}Fe+{sup 208}Pb reaction the quasifission process dominates at all measured energies.

  8. Swift Heavy Ion Induced Defect Study in Epitaxial n-Type CaAs from {In} {Situ} Hall Effect Measurements

    NASA Astrophysics Data System (ADS)

    Mikou, M.; Carin, R.; Bogdanski, P.; Marie, P.

    1997-08-01

    N-type (Si-doped, N_D ≈ 10^{17} cm^{-3}) GaAs epitaxial layers (MOCVD) are irradiated at 77 K with oxygen (0.163 GeV), krypton (5.15 GeV), xenon (5.73 GeV) and at 300 K with krypton (5.15 GeV). Hall effect measurements are performed, in situ, with increasing fluence. A decrease of the electron concentration and a degradation of the Hall mobility, respectively due to trapping and to scattering on irradiation-induced point defects are pointed out. In the heavily doped layers, shallow donor impurities merge with the conduction band in distorted band tail. A simple two band conduction model is used as a simulation tool, which allows the carrier Hall concentration variation to be correctly fitted, as a function of both temperature and ion fluence. The Hall mobility versus fluence variation at 77 K, which is mainly limited by screened ionized impurities and defects, is also simulated. From these simulations, the arsenic vacancy levels E_1 and E_2 are most likely to correspond respectively to single acceptor (-/0) and single donor (0/+) transitions. The introduction rates of induced defects (in particular V_As) are estimated: the total experimental introduction rate appears to be about 50% of the theoretical atomic displacement rate associated with nuclear collisions, independently of ion nature and of temperature. Although electronic stopping power S_e is about 2000 times larger than nuclear stopping power S_n, it is then suggested that irradiation-induced electronic excitation, in the investigated range S_e = 1 12 MeV/μm, has no effect on the degradation of n-type GaAs epitaxial layers. Des couches épitaxiées de GaAs de type n (dopage au silicium, N_D ≈ 10^{17} cm^{-3}) sont irradiées à 77 K avec des ions oxygène (0,163 GeV), krypton (5,15 GeV), xénon (5,73 GeV) et à 300 K avec des ions krypton (5,15 GeV). Les mesures d'effet Hall sont effectuées in situ, au fur et à mesure de l'accroissement de fluence. On observe une diminution de la concentration électronique et une dégradation de la mobilité de Hall, respectivement dues au piégeage et à la diffusion des électrons sur les défauts ponctuels créés par l'irradiation. Dans de telles couches fortement dopées, les niveaux d'impuretés dopantes (donneurs peu profonds) sont engloutis dans une queue distordue de la bande de conduction. Un modèle simple de conduction à deux bandes permet de simuler correctement les variations expérimentales de la concentration de Hall à la fois en fonction de la température et de la fluence des ions. On simule également les variations de mobilité de Hall avec la fluence à 77 K car à cette température, la diffusion est principalement due aux impuretés et défauts ionisés. A partir de ces simulations, il apparaît que les niveaux E_1 et E_2 de la lacune d'arsenic correspondent vraisemblablement aux transitions simple accepteur (-/0) et simple donneur (0/+). Une estimation des taux de production de défauts est effectuée : la quantité totale de défauts détectés est égale à eriviron 50 % du nombre théorique de déplacements atomiques provoqués par les collisions nucléaires, indépendamment du type d'ion incident et de la température. Bien que le pouvoir d'arrêt électronique S_e soit environ 2000 fois plus grand que le pouvoir d'arrêt nucléaire S_n, il semble que, dans la gamme explorée S_e = 1 12 MeV/μm, l'excitation électronique induite par l'irradiation n'ait pas d'incidence sur la dégradation des couches épitaxiées de GaAs de type n.

  9. Heavy ion-induced SEEs on 130 nm CMOS technology for LHC application—status and challenges

    NASA Astrophysics Data System (ADS)

    Gabrielli, A.

    2011-12-01

    This work summarizes the status of the art of electronic designs, using CMOS technologies, to stand LHC and S-LHC radiation-hard environments. Radiation effects can be divided into Single Event Effects and Total Ionizing Dose effects, which are consequences of different interaction effects within the silicon and the electronics. These types of effects are commonly investigated and faced separately. The commercial 130 nm CMOS technology, today primarily proposed for SLHC electronic upgrades, only implements redundancies against the Single Event Effects`. On the contrary, the 250 nm technology node used in the past years for LHC experiments, was also hardened against the Total Ionizing Dose. Hence, the choice of the technology to be used for high-energy experiments is very crucial as it implies huge efforts in the designs of the components. In addition, an unavoidable technology scaling keeps moving toward ever-smaller sizes and this affects the availability of the silicon process for medium and long-term experiments.

  10. Mammary gland: From embryogenesis to adult life.

    PubMed

    Musumeci, Giuseppe; Castrogiovanni, Paola; Szychlinska, Marta Anna; Aiello, Flavia Concetta; Vecchio, Giada Maria; Salvatorelli, Lucia; Magro, Gaetano; Imbesi, Rosa

    2015-01-01

    The aim of this review is to focus on the molecular factors that ensure the optimal development and maintenance of the mammary gland thanks to their integration and coordination. The development of the mammary gland is supported, not only by endocrine signals, but also by regulatory molecules, which are able to integrate signals from the surrounding microenvironment. A major role is certainly played by homeotic genes, but their incorrect expression during the spatiotemporal regulation of proliferative, functional and differentiation cycles of the mammary gland, may result in the onset of neoplastic processes. Attention is directed also to the endocrine aspects and sexual dimorphism of mammary gland development, as well as the role played by ovarian steroids and their receptors in adult life.

  11. Gordon Research Conference on Mammary Gland Biology

    SciTech Connect

    Not Available

    1989-01-01

    The 1989 conference was the tenth in the series of biennial Gordon Research Conferences on Mammary Gland Biology. Traditionally this conference brings together scientists from diverse backgrounds and experience but with a common interest in the biology of the mammary gland. Investigators from agricultural and medical schools, biochemists, cell and molecular biologists, endocrinologists, immunologists, and representatives from the emerging biotechnology industries met to discuss current concepts and results on the function and regulation of the normal and neoplastic mammary gland in a variety of species. Of the participants, approximately three-fourths were engaged in studying the normal mammary gland function, whereas the other quarter were engaged in studying the neoplastic gland. The interactions between scientists, clinicians, veterinarians examining both normal and neoplastic cell function serves to foster the multi-disciplinary goals of the conference and has stimulated many cooperative projects among participants in previous years.

  12. Trace element transport in the mammary gland.

    PubMed

    Lönnerdal, Bo

    2007-01-01

    The mammary gland has a remarkable capacity to adapt to maternal deficiency or excess of iron, copper, and zinc and to homeostatically control milk concentrations of these essential nutrients. Similarly, it can regulate changes in concentrations of iron, copper, and zinc change during lactation. For iron, this regulation is achieved by transferrin receptor, DMT1, and ferroportin, whereas mammary gland copper metabolism is regulated by Ctr1, ATP7A, and ATP7B. Zinc homeostasis is complex, involving both zinc importers (Zip3) and zinc exporters (ZnT-1, ZnT-2, and ZnT-4). Both transcriptional and post-translational regulation can affect protein abundance and cellular localization of these transporters, finely orchestrating uptake, intracellular trafficking, and secretion of iron, copper, and zinc. The control of mammary gland uptake and milk secretion of iron, copper, and zinc protects both the mammary gland and the breast-fed infant against deficiency and excess of these nutrients.

  13. The mammary cellular hierarchy and breast cancer.

    PubMed

    Oakes, Samantha R; Gallego-Ortega, David; Ormandy, Christopher J

    2014-11-01

    Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and regulation of the mammary cellular hierarchy and we describe the development of the concepts that have guided our investigations. We outline recent advances in in vivo lineage tracing that is now challenging many of our assumptions regarding the behavior of mammary stem cells, and we show how understanding these cellular lineages has altered our view of breast cancer.

  14. Mammary fibroadenoma in a lamb

    PubMed Central

    Guvenc, Tolga; Yarim, Murat; Kabak, Yonca B.; Sozgen, Yuksel

    2007-01-01

    A fibroadenoma was diagnosed in the left udder of a 3-month-old female Chios lamb. No recurrence was observed after surgery. Grossly, the tumor had a whitish-gray lobular appearance, and the lobules were interlaced with thin septa. Microscopically, the tumor was composed of proliferating fibroepithelial tissue, including differentiated ducts lined by whorls and interlacing bundles of abundant loose fibrovascular stroma. Immunohistochemistry revealed the ductal epithelium to be positive for pancytokeratin (AE1/AE3) and loose fibrovascular stroma was positive for vimentin and basal cells covering the ductal epithelium of alpha-smooth-muscle actin. Immunostaining for the estrogen and progesterone receptors was negative. A diagnosis of mammary fibroadenoma was made based on the histological and immunohistochemical findings. PMID:17993758

  15. Effects of temperature on the ion-induced bending of germanium and silicon nanowires

    NASA Astrophysics Data System (ADS)

    Camara, Osmane; Hanif, Imran; Tunes, Matheus; Harrison, Robert; Greaves, Graeme; Donnelly, Stephen; Hinks, Jonathan

    2017-07-01

    Nanowires can be manipulated using an ion beam via a phenomenon known as ion-induced bending (IIB). While the mechanisms behind IIB are still the subject of debate, accumulation of point defects or amorphisation are often cited as possible driving mechanisms. Previous results in the literature on IIB of Ge and Si nanowires have shown that after irradiation the aligned nanowires are fully amorphous. Experiments were recently reported in which crystalline seeds were preserved in otherwise-amorphous ion-beam-bent Si nanowires which then facilitated solid-phase epitaxial growth (SPEG) during subsequent annealing. However, the ion-induced alignment of the nanowires was lost during the SPEG. In this work, in situ ion irradiations in a transmission electron microscope at 400 °C and 500 °C were performed on Ge and Si nanowires, respectively, to supress amorphisation and the build-up of point defects. Both the Ge and Si nanowires were found to bend during irradiation thus drawing into question the role of mechanisms based on damage accumulation under such conditions. These experiments demonstrate for the first time a simple way of realigning single-crystal Ge and Si nanowires via IIB whilst preserving their crystal structure.

  16. Experimental evidence of ion-induced instabilities in the NSLS-II storage ring

    NASA Astrophysics Data System (ADS)

    Cheng, Weixing; Li, Yongjun; Podobedov, Boris

    2017-07-01

    Fast ion instability has been identified as one of the most prominent instabilities in the recently constructed NSLS-II storage ring at Brookhaven National Laboratory. At a relatively low beam current ( 25 mA) multi-bunch fills, ion-induced instabilities have already been observed during the early stages of machine commissioning. At present user operation with 250 mA in 1000 bunches, the fast ion still remains the dominant instability, even after months of vacuum conditioning at high current. Ion-induced dipole motions of the electron beam have been suppressed using the transverse bunch-by-bunch (BxB) feedback system. However other adverse effects of this instability, such as the vertical beam size increase along the bunch train cannot be cured by the feedback system. Therefore, to achieve the NSLS-II design current of 500 mA while maintaining a small vertical beam emittance, it is important to further understand the fast ion instability and develop mitigation techniques. This paper reports on a series of ion-instability observations at various fill patterns and beam currents using start-of-art NSLS-II diagnostic tools.

  17. Composite alginate hydrogel microparticulate delivery system of zidovudine hydrochloride based on counter ion induced aggregation

    PubMed Central

    Roy, Harekrishna; Rao, P. Venkateswar; Panda, Sanjay Kumar; Biswal, Asim Kumar; Parida, Kirti Ranjan; Dash, Jharana

    2014-01-01

    Aim: The present study deals with preparation of zidovudine loaded microparticle by counter ion induced aggregation method. During this study effect of polyacrylates and hypromellose polymers on release study were investigated. Materials and Methods: The ion induced aggregated alginate based microparticles were characterized for surface morphology, particle size analysis, drug entrapment study, in-vitro study, Fourier-transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC) study. Results and Discussion: The result showed Eudragit RL-100 (ERL) based formulations had smoother surface as well as their mean particle sizes were found greater compared with Eudragit RS-100 (ERS) microparticles. Furthermore, drug entrapments were found to be more in ERL formulae as compared with ERS. RL3 released 101.05% drug over a period of 8th h and followed Higuchi profile and Fickian diffusion. Moreover, data obtained illustrated that, higher amount of quaternary ammonium group, alkali value, and glass transition temperature may be possible reason for improving permeability of ERL based formulations. It was also noticed, hyroxypropyl methylcellulose (HPMC) K4M premium grade polymer sustained drug release more than HPMC K15M. In addition, drug-excipient interaction study was carried out by FTIR and DSC study. PMID:25298940

  18. Beam Energy Scaling of Ion-Induced Electron Yield from K+ Impact on Stainless Steel

    SciTech Connect

    Covo, M K; Molvik, A; Friedman, A; Westenskow, G; Barnard, J J; Cohen, R; Seidl, P; Kwan, J W; Logan, G; Baca, D; Bieniosek, F; Celata, C M; Vay, J; Vujic, J L

    2006-03-06

    Electron clouds limit the performance of many major accelerators and storage rings. Significant quantities of electrons result when halo ions are lost to beam tubes, generating gas which can be ionized and ion-induced electrons that can multiply and accumulate, causing degradation or loss of the ion beam. In order to understand the physical mechanisms of ion-induced electron production, experiments studied the impact of 50 to 400 keV K{sup +} ions on stainless steel surfaces near grazing incidence, using the 500 kV Ion Source Test Stand (STS-500) at LLNL. The experimental electron yield scales with the electronic component (dE{sub e}/dx) of the stopping power and its angular dependence does not follow l/cos({theta}). A theoretical model is developed, using TRIM code to evaluate dE{sub e}/dx at several depths in the target, to estimate the electron yield, which is compared with the experimental results. The experiment extends the range of energy from previous works and the model reproduces the angular dependence and magnitude of the electron yield.

  19. Pleiotrophin (PTN) Expression and Function and in the Mouse Mammary Gland and Mammary Epithelial Cells

    PubMed Central

    Rosenfield, Sonia M.; Bowden, Emma T.; Cohen-Missner, Shani; Gibby, Krissa A.; Ory, Virginie; Henke, Ralf T.; Riegel, Anna T.; Wellstein, Anton

    2012-01-01

    Expression of the heparin-binding growth factor, pleiotrophin (PTN) in the mammary gland has been reported but its function during mammary gland development is not known. We examined the expression of PTN and its receptor ALK (Anaplastic Lymphoma Kinase) at various stages of mouse mammary gland development and found that their expression in epithelial cells is regulated in parallel during pregnancy. A 30-fold downregulation of PTN mRNA expression was observed during mid-pregnancy when the mammary gland undergoes lobular-alveolar differentiation. After weaning of pups, PTN expression was restored although baseline expression of PTN was reduced significantly in mammary glands of mice that had undergone multiple pregnancies. We found PTN expressed in epithelial cells of the mammary gland and thus used a monoclonal anti-PTN blocking antibody to elucidate its function in cultured mammary epithelial cells (MECs) as well as during gland development. Real-time impedance monitoring of MECs growth, migration and invasion during anti-PTN blocking antibody treatment showed that MECs motility and invasion but not proliferation depend on the activity of endogenous PTN. Increased number of mammospheres with laminin deposition after anti-PTN blocking antibody treatment of MECs in 3D culture and expression of progenitor markers suggest that the endogenously expressed PTN inhibits the expansion and differentiation of epithelial progenitor cells by disrupting cell-matrix adhesion. In vivo, PTN activity was found to inhibit ductal outgrowth and branching via the inhibition of phospho ERK1/2 signaling in the mammary epithelial cells. We conclude that PTN delays the maturation of the mammary gland by maintaining mammary epithelial cells in a progenitor phenotype and by inhibiting their differentiation during mammary gland development. PMID:23077670

  20. Polarized dermoscopy of mammary Paget disease*

    PubMed Central

    de Crignis, Giselly Silva Neto; de Abreu, Luciana; Buçard, Alice Mota; Barcaui, Carlos Baptista

    2013-01-01

    Mammary Paget's disease is a rare intraepithelial adenocarcinoma, located on the nipple/areola complex, highly associated with breast cancer. Although the international literature emphasizes the dermatoscopic pattern of mammary Paget's disease pigmented variant, the authors describe the dermoscopic findings of classical Paget's disease and demonstrate the presence of chrysalis-like structures, criteria recently described in the literature and not yet reported in Paget's disease. PMID:23739693

  1. Mammary Cancer and Activation of Transposable Elements

    DTIC Science & Technology

    2015-03-01

    transcriptionally activated during pregnancy and lactation , and the mice are predisposed to develop mammary cancer after a minimum of 3 pregnancies and...pregnancy and lactation . After 3 pregnancies and lactations , but not after 1 pregnancy and lactation , females develop mammary cancers at an average...mated females per experimental condition (1 or 3 pregnancies/ lactations . 5 breeding strategy to develop triple transgenic cancer -prone and control

  2. Identification of Mammary Specific Transcription Factors.

    DTIC Science & Technology

    1998-01-01

    per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and...release; distribution unlimited 12b. DISTRIBUTION CODE 13. ABSTRACT (Maximum 200 words) The Mouse Mammary Tumor Virus (MMTV) achieves its highest...levels of expression in the mammary glands of lactating mice . Previous work showed that the MMTV Long Terminal Repeat (LTR) has a modest level of

  3. Characterization of Human Mammary Epithelial Stem Cells

    DTIC Science & Technology

    2007-10-01

    Epithelial Stem Cells PRINCIPAL INVESTIGATOR: Peter D. Eirew CONTRACTING ORGANIZATION: British Columbia Cancer Agency...NUMBER Characterization of Human Mammary Epithelial Stem Cells 5b. GRANT NUMBER W81XWH-06-1-0702 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Abstract The mammary epithelium in normal adult female mice contains undifferentiated stem cells with extensive in vivo regenerative and self-renewal

  4. Stem cells and the developing mammary gland.

    PubMed

    Makarem, Maisam; Spike, Benjamin T; Dravis, Christopher; Kannan, Nagarajan; Wahl, Geoffrey M; Eaves, Connie J

    2013-06-01

    The mammary gland undergoes dynamic changes throughout life. In the mouse, these begin with initial morphogenesis of the gland in the mid-gestation embryo followed by hormonally regulated changes during puberty and later in adulthood. The adult mammary gland contains a hierarchy of cell types with varying potentials for self-maintenance and differentiation. These include cells able to produce complete, functional mammary glands in vivo and that contain daughter cells with the same remarkable regenerative potential, as well as cells with more limited clonogenic activity in vitro. Here we review how applying in vitro and in vivo methods for quantifying these cells in adult mammary tissue to fetal mammary cells has enabled the first cells fulfilling the functional criteria of transplantable, isolated mammary stem cells to be identified a few days before birth. Thereafter, the number of these cells increases rapidly. Populations containing these fetal stem cells display growth and gene expression programs that differ from their adult counterparts but share signatures characteristic of certain types of breast cancer. Such observations reinforce growing evidence of important differences between tissue-specific fetal and adult cells with stem cell properties and emphasize the merits of investigating their molecular basis.

  5. Morphological and histological characteristics of mammary dysplasias occurring in cell dissociation-derived murine mammary outgrowths

    SciTech Connect

    Ethier, S.P.; Adams, L.M.; Ullrich, R.L.

    1984-10-01

    The morphological and histological characteristics of ductal dysplasias that were observed in mammary outgrowths derived from monodispersed mammary cells of carcinogen-treated mice are described. Mammary outgrowths were derived by injecting either 10(4) or 10(5) enzymatically dissociated mammary cells, obtained from control or carcinogen-treated BALB/c mice, into gland-free mammary fat pads of syngeneic hosts. The mammary dysplasias observed varied considerably in morphological and histological characteristics. The majority of the lesions were ductal in origin and were associated with epithelial hyperplasia which ranged from mild hyperplasia, in which only a few extra layers of epithelium were present, to severe hyperplasia, in which the ducts and end buds were occluded and distended with epithelial cells. In addition, papillary and lobular lesions were observed which were also associated with varying degrees of hyperplasia. The range of mammary dysplasias observed in these outgrowths closely resembles that of lesions associated with the pathogenesis of mammary carcinoma in mice, rats, and humans.

  6. Prevalence of Glomerulopathies in Canine Mammary Carcinoma

    PubMed Central

    2016-01-01

    The incidence and prevalence of paraneoplastic glomerulopathy, especially associated with carcinoma, are a matter of debate and the causal link between cancer and glomerular diseases remains unclear. The aim of this study was to evaluate renal biopsies of selected bitches with spontaneous mammary gland carcinoma. We hypothesized that dogs with mammary carcinomas would show histologic evidence of glomerular pathology. A prospective study was performed in dogs with naturally occurring mammary carcinoma that were undergoing tumor resection and ovariohysterectomy. We evaluated renal biopsies of 32 bitches with spontaneous mammary gland carcinoma and 11 control dogs without mammary gland neoplasia. Samples were obtained from the left kidney and the biopsy material was divided for light microscopy (LM), immunofluorescence (IF) and transmission electron microscopy (TEM). Light microscopy abnormalities were identified in 78.1% of dogs with mammary carcinoma (n = 25) and in none of the dogs in the control group. Focal glomerular mesangial matrix expansion was the most common alteration (n = 15, 60.0%), but mesangial cell proliferation (n = 9, 36.0%) and focal segmental glomerulosclerosis (n = 9, 36.0%), synechiae (n = 7, 28.0%), and globally sclerotic glomeruli (n = 6, 24.0%) were also frequent in dogs with malignancy. Immunofluorescence microscopy revealed strong IgM staining was demonstrated in 64.3% (n = 18) of carcinoma dogs. Transmission electron microscopy from dogs with carcinoma revealed slight changes, the most frequent of which was faint sub-endothelial and mesangial deposits of electron-dense material (78%). Mesangial cell interpositioning and segmental effacement of podocyte foot processes were identified in some specimens (45%). Changes in the glomerulus and proteinuria are common in dogs with naturally occurring mammary carcinoma and this condition appears to provide an excellent large animal model for cancer-associated glomerulopathy in humans. PMID:27764139

  7. Hormone signaling requirements for the conversion of non-mammary mouse cells to mammary cell fate(s) in vivo.

    PubMed

    Boulanger, Corinne A; Rosenfield, Sonia M; George, Andrea L; Smith, Gilbert H

    2015-06-01

    Mammotropic hormones and growth factors play a very important role in mammary growth and differentiation. Here, hormones including Estrogen, Progesterone, Prolactin, their cognate receptors, and the growth factor Amphiregulin, are tested with respect to their roles in signaling non-mammary cells from the mouse to redirect to mammary epithelial cell fate(s). This was done in the context of glandular regeneration in pubertal athymic female mice. Our previous studies demonstrated that mammary stem cell niches are recapitulated during gland regeneration in vivo. During this process, cells of exogenous origin cooperate with mammary epithelial cells to form mammary stem cell niches and thus respond to normal developmental signals. In all cases tested with the possible exception of estrogen receptor alpha (ER-α), hormone signaling is dispensable for non-mammary cells to undertake mammary epithelial cell fate(s), proliferate, and contribute progeny to chimeric mammary outgrowths. Importantly, redirected non-mammary cell progeny, regardless of their source, have the ability to self-renew and contribute offspring to secondary mammary outgrowths derived from transplanted chimeric mammary fragments; thus suggesting that some of these cells are capable of mammary stem cell/progenitor functions.

  8. Comparative aspects of mammary gland development and homeostasis.

    PubMed

    Capuco, Anthony V; Ellis, Steven E

    2013-01-01

    Mammary glands are crucial to the reproductive strategy of mammals, and the milk of domesticated ruminants serves as an important source of nutrients for the human population. The majority of mammary gland development occurs postnatally, and the mammary gland undergoes cyclical periods of growth, differentiation, lactation, and regression that are coordinated to provide nutrients for offspring or are driven by strategies to manage reproduction and milk production of domesticated species. Growth and maintenance of the mammary epithelium depends on the function of mammary stem cells and progenitor cells. In this review, we provide an overview of postnatal mammary gland development, cyclical phases of mammary gland regression (regression during lactation and between successive lactations), and mammary stem cells and progenitor cells. Where possible, these processes are related to animal production and compared across species, particularly bovine, porcine, murine, and human.

  9. Mammary duct ectasia: a cause of bloody nipple discharge.

    PubMed Central

    Leung, Alexander K. C.; Kao, C. Pion

    2004-01-01

    We report a 13-year-old girl with bloody nipple discharge as a result of mammary duct ectasia. Our patient is the second reported case of mammary duct ectasia in a pubertal girl. Images Figure 1 PMID:15101674

  10. Molecular dynamics study of accelerated ion-induced shock waves in biological media

    NASA Astrophysics Data System (ADS)

    de Vera, Pablo; Mason, Nigel J.; Currell, Fred J.; Solov'yov, Andrey V.

    2016-09-01

    We present a molecular dynamics study of the effects of carbon- and iron-ion induced shock waves in DNA duplexes in liquid water. We use the CHARMM force field implemented within the MBN Explorer simulation package to optimize and equilibrate DNA duplexes in liquid water boxes of different sizes and shapes. The translational and vibrational degrees of freedom of water molecules are excited according to the energy deposited by the ions and the subsequent shock waves in liquid water are simulated. The pressure waves generated are studied and compared with an analytical hydrodynamics model which serves as a benchmark for evaluating the suitability of the simulation boxes. The energy deposition in the DNA backbone bonds is also monitored as an estimation of biological damage, something which is not possible with the analytical model.

  11. Microstructural evolution in H ion induced splitting of freestanding GaN

    NASA Astrophysics Data System (ADS)

    Moutanabbir, O.; Scholz, R.; Senz, S.; Gösele, U.; Chicoine, M.; Schiettekatte, F.; Süßkraut, F.; Krause-Rehberg, R.

    2008-07-01

    We investigated the microstructural transformations during hydrogen ion-induced splitting of GaN thin layers. Cross-sectional transmission electron microscopy and positron annihilation spectroscopy data show that the implanted region is decorated with a high density of 1-2nm bubbles resulting from vacancy clustering during implantation. These nanobubbles persist up to 450°C. Ion channeling data show a strong dechanneling enhancement in this temperature range tentatively attributed to strain-induced lattice distortion. The dechanneling level decreases following the formation of plateletlike structures at 475°C. Extended internal surfaces develop around 550°C leading to the exfoliation of GaN thin layer.

  12. Impact of helium implantation and ion-induced damage on reflectivity of molybdenum mirrors

    NASA Astrophysics Data System (ADS)

    Garcia-Carrasco, A.; Petersson, P.; Hallén, A.; Grzonka, J.; Gilbert, M. R.; Fortuna-Zalesna, E.; Rubel, M.

    2016-09-01

    Molybdenum mirrors were irradiated with Mo and He ions to simulate the effect of neutron irradiation on diagnostic first mirrors in next-generation fusion devices. Up to 30 dpa were produced under molybdenum irradiation leading to a slight decrease of reflectivity in the near infrared range. After 3 × 1017 cm-2 of helium irradiation, reflectivity decreased by up to 20%. Combined irradiation by helium and molybdenum led to similar effects on reflectivity as irradiation with helium alone. Ion beam analysis showed that only 7% of the implanted helium was retained in the first 40 nm layer of the mirror. The structure of the near-surface layer after irradiation was studied with scanning transmission electron microscopy and the extent and size distribution of helium bubbles was documented. The consequences of ion-induced damage on the performance of diagnostic components are discussed.

  13. Temperature dependence for ion-induced amorphization of NiAl

    NASA Astrophysics Data System (ADS)

    Jaouen, C.; Rivière, J. P.; Delafond, J.

    1991-07-01

    Crystalline NiAl films of equiatomic composition were irradiated with 360 keV Xe + ions in the temperature range 4-300 K. The amorphous volume fraction was monitored continuously as a function of ion dose from in situ electrical resistivity measurements. The experimental results indicate that the ion-induced amorphization occurs always by a direct (i.e. intracascade) mechanism. The ion dose necessary for producing complete disorder (i.e. amorphization) increases rapidly between 77 and 120 K. Above these temperatures, the amorphous volume fraction reaches a saturation value lower than 1, indicating that total amorphization is never obtained. The damage cross-sectional area decreases with increasing temperature and this behavior is analyzed by Morehead and Crowder's model. These results suggest that there is under irradiation a competition between ballistic amorphization and heterogeneous irradiation-enhanced crystallization.

  14. Prooxidant and antioxidant effects of Trolox on ferric ion-induced oxidation of erythrocyte membrane lipids.

    PubMed

    Ko, K M; Yick, P K; Poon, M K; Ip, S P

    1994-12-07

    The prooxidant and antioxidant actions of Trolox were examined in an in vitro system measuring ferric ion-induced oxidation of erythrocyte membrane lipids. Trolox was found to produce a concentration-dependent biphasic effect on the ferric ion-stimulated lipid peroxidation, with the mode of action being similar to those produced by reducing-agent antioxidants, such as ascorbic acid and reduced glutathione, and iron chelator, such as desferrioxamine. Phytic acid, a potent iron chelator, could suppress the prooxidant actions of Trolox and desferrioxamine, but not those of ascorbic acid and reduced glutathione. The ability of Trolox to stimulate ferric ion-catalyzed ascorbate oxidation, as similar to the action produced by ethylenediaminetetraacetic acid, indicates the presence of iron-chelating activity. The ensemble of results suggests the possible involvement of iron chelation in the prooxidant action of Trolox in ferric ion-stimulated lipid peroxidation reactions.

  15. Potential for ion-induced nucleation of volatile organic compounds by radon decay in indoor environments

    SciTech Connect

    Daisey, J.M.

    1991-11-01

    There is considerable interest in the unattached'' fraction of radon progeny in indoor air because of its significance to the estimation of the risks of radon exposure. Because of its high mobility in air, the unattached fraction is more efficiently deposited in the respiratory tract. Variation in the diameter of the unattached'' fraction and in its diffusion coefficient can be due to clustering of other atmospheric species around the {sup 218}PoO{sub 2}{sup +} ion. The purpose of this study was to investigate the potential for the formation of clusters of vapor phase organic compounds, found in indoor air, around the {sup 218}PoO{sub 2}{sup +} ion and to determine which were most likely to form clusters. A secondary purpose was to provide a compilation of measurements of indoor organic compounds for future experiments and theoretical calculations by the radon research community. The classical charged liquid droplet theory (Thomson equation) was used to estimate the Gibbs free energy of ion-induced nucleation and to provide an indication of the indoor organic compounds most likely to undergo ion-induced nucleation. Forty-four volatile and semi-volatile organic compounds out of the more than 300 which have been reported in indoor air were investigated. Water vapor was included for comparison. The results indicate that there is a potential for the formation of clusters of organic compounds around the {sup 218}PoO{sub 2}{sup +} ion. The compounds with the greatest potential for cluster formation are the volatile oxidized hydrocarbons (e.g., n-butanol, phenol, hexanal, nonanal, benzaldehyde, the ketones and the acetates) and the semi-volatile organic compounds (pentachlorophenol, nicotine, chlordane, chlorpyrifos).

  16. Potential for ion-induced nucleation of volatile organic compounds by radon decay in indoor environments

    SciTech Connect

    Daisey, J.M.

    1991-11-01

    There is considerable interest in the ``unattached`` fraction of radon progeny in indoor air because of its significance to the estimation of the risks of radon exposure. Because of its high mobility in air, the unattached fraction is more efficiently deposited in the respiratory tract. Variation in the diameter of the ``unattached`` fraction and in its diffusion coefficient can be due to clustering of other atmospheric species around the {sup 218}PoO{sub 2}{sup +} ion. The purpose of this study was to investigate the potential for the formation of clusters of vapor phase organic compounds, found in indoor air, around the {sup 218}PoO{sub 2}{sup +} ion and to determine which were most likely to form clusters. A secondary purpose was to provide a compilation of measurements of indoor organic compounds for future experiments and theoretical calculations by the radon research community. The classical charged liquid droplet theory (Thomson equation) was used to estimate the Gibbs free energy of ion-induced nucleation and to provide an indication of the indoor organic compounds most likely to undergo ion-induced nucleation. Forty-four volatile and semi-volatile organic compounds out of the more than 300 which have been reported in indoor air were investigated. Water vapor was included for comparison. The results indicate that there is a potential for the formation of clusters of organic compounds around the {sup 218}PoO{sub 2}{sup +} ion. The compounds with the greatest potential for cluster formation are the volatile oxidized hydrocarbons (e.g., n-butanol, phenol, hexanal, nonanal, benzaldehyde, the ketones and the acetates) and the semi-volatile organic compounds (pentachlorophenol, nicotine, chlordane, chlorpyrifos).

  17. A new setup for elastic recoil analysis using ion induced electron emission for particle identification

    NASA Astrophysics Data System (ADS)

    Steinbauer, E.; Benka, O.; Steinbatz, M.

    1998-03-01

    We describe a new setup for elastic recoil detection analysis (ERDA) using our recently developed particle identification method. Before the ions and elastic recoil atoms from the target reach a silicon surface barrier detector for energy analysis, they penetrate a set of thin foils (e.g. carbon). The ion induced electron emission yield from the foils depends on the nuclear charge of the penetrating ion and it is roughly proportional to the energy loss in the foil. The emitted electrons are accelerated towards a microchannel plate (MCP), which gives a signal amplitude proportional to the number of emitted electrons. This signal is measured in coincidence with the energy signal from the surface barrier detector using our dual-parameter multichannel analyzer system M2D. Since the energy resolution is not measurably deteriorated by the particle identification our setup offers optimum depth resolution for light elements. Due to the compact design large solid angles for high sensitivity can be achieved. A new measuring chamber has been built which offers considerable improvements. The ERDA scattering angle (30° or 45°) and the target orientation can be selected for optimum depth resolution or sensitivity. Element separation for light elements has been enhanced by several improvements: A new geometry of the foil setup improves the collection efficiency for ion induced electrons onto the MCP, coating of the carbon foils with insulators enhances the electron emission yield. Finally, a new data evaluation procedure has been developed in which the pulse height spectrum of the MCP is considered to be a linear combination of individual spectra from the incident ion and of the recoil atoms. The normalized shapes of these spectra are taken from calibration measurements, the intensities are then calculated using a linear fitting algorithm and finally give the depth profiles of the elements in the target. For hydrogen in near surface layers even isotopic separation is possible

  18. USF-1 as an Inhibitor of Mammary Gland Carcinogenesis

    DTIC Science & Technology

    2002-09-01

    was targeted to the mammary gland under the control of the mouse mammary tumor virus (mmtv) long terminal repeat. Of eight lines of transgenic mice ...be explored by testing the hypothesis that targeted overexpression of USF-2 in the mammary glands of MMTV-myc transgenic mice will cause withdrawal...USF-2 under the control of the mouse mammary tumor virus long terminal repeat. Once in hand this new line of transgenic mice would be crossed with a

  19. [Galactorrhea after mammary plastic surgery].

    PubMed

    Inguenault, C; Capon-Degardin, N; Martinot-Duquennoy, V; Pellerin, P

    2005-04-01

    Galactorrhoea is a complication rarely observed after mammary plastic surgery. Our experience in the domain extends to three clinical cases - two after prosthetic insertion and one after breast reduction - wich will be presented here. The origin of this complication is uncertain. Nevertheless, it is likely to be multifocal, as surgery alone is not the only cause. Postsurgical galactorrhoea often follows a benign course culminating in spontaneous resolution. However, it may reveal the presence of o prolactin secreting adenoma, as was the case with one of our patients. A detailed history, exploring antecedent factors, is an essential step in guiding subsequent management. When faced with postsurgical galactorrhoea, serum prolactin levels should be measured. If serum prolactin levels exceed 150 ng/ml further investigation by way of an MRI of the sella turcica is advisable to rule out pituitary adenoma. Depending on symptom severity, treatment may be medical with the prescription of dopaminergic agonists, and/or surgical with drainage or removal of prostheses. Increased awareness of galactorrhea as a possible complication of plastic surgery to the breast will improve management.

  20. Pigmented mammary paget disease misdiagnosed as malignant melanoma.

    PubMed

    Lee, Ji Hye; Kim, Tae Hyung; Kim, Soo-Chan; Kim, You Chan; Roh, Mi Ryung

    2014-12-01

    Pigmented mammary Paget disease is a very rare clinicopathologic variant of mammary Paget disease. Diagnosis is often difficult because its clinical and histological features are very similar to those of malignant melanoma. Herein, we report a case of pigmented mammary Paget disease misdiagnosed as malignant melanoma.

  1. Comparative aspects of mammary gland development and homeostasis

    USDA-ARS?s Scientific Manuscript database

    Mammary glands are crucial to the reproductive strategy of mammals and the milk of domesticated ruminants serves as an important source of nutrients for the human population. The majority of mammary gland development occurs postnatally and the mammary gland undergoes cyclical periods of growth, dif...

  2. Cutaneous metastases of a mammary carcinoma in a llama.

    PubMed Central

    Leichner, T L; Turner, O; Mason, G L; Barrington, G M

    2001-01-01

    An 8-year-old, female llama was evaluated for nonhealing, ulcerative, cutaneous lesions, which also involved the mammary gland. Biopsies of the lesions distant from and within the mammary gland area revealed an aggressive carcinoma. The tumor was confirmed at necropsy to be a mammary gland adenocarcinoma with cutaneous metastasis. Images Figure 1. PMID:11265189

  3. Mammary phenotypic expression induced in epidermal cells by embryonic mammary mesenchyme.

    PubMed

    Cunha, G R; Young, P; Christov, K; Guzman, R; Nandi, S; Talamantes, F; Thordarson, G

    1995-01-01

    The goal of this research was to establish methods for inducing mammary epithelial differentiation from nonmammary epithelium. For this purpose, mid-ventral or dorsal epidermis (skin epithelium; SKE) from 13-day rat or mouse embryos was associated with 13-day embryonic mouse mammary mesenchyme (mammary gland mesenchyme; MGM) (mouse MGM+rat or mouse SKE). The resultant MGM+SKE recombinants as well as controls (homotypic mouse mammary recombinants, homotypic mouse skin recombinants and mouse mammary mesenchyme by itself) were grafted under the renal capsule of syngeneic or athymic female nude mouse hosts. Most female hosts were induced to undergo lactogenesis by grafting an adult pituitary which elicited a state of hyperprolactinemia. Tissue recombinants of mouse MGM+rat or mouse SKE grown for 1 month in vivo formed a hair-bearing keratinized skin from which mammary ductal structures extended into the mesenchyme. The ducts were composed of columnar luminal epithelial cells as well as basal, actin-positive myoepithelial cells. When grown in pituitary-grafted hosts, the ductal epithelial cells expressed casein and alpha-lactalbumin as judged by immunocytochemistry. The expression of caseins in MGM+SKE recombinants was confirmed by Western blot. The epithelial cells in mouse MGM+rat SKE recombinants expressing milk proteins were shown to be rat cells while the surrounding connective tissue was composed of mouse cells based upon staining with Hoechst dye 33258. Using mammary-specific markers, these studies confirmed the earlier morphological studies of Propper and unequivocally demonstrated for the first time that embryonic mammary mesenchyme can induce morphological and functional mammary differentiation from nonmammary epithelium.

  4. Of Microenvironments and Mammary Stem Cells

    SciTech Connect

    LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J

    2007-06-01

    In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

  5. Mammary stem cells have myoepithelial cell properties

    PubMed Central

    Prater, Michael D.; Petit, Valérie; Russell, I. Alasdair; Giraddi, Rajshekhar; Shehata, Mona; Menon, Suraj; Schulte, Reiner; Kalajzic, Ivo; Rath, Nicola; Olson, Michael F.; Metzger, Daniel; Faraldo, Marisa M.; Deugnier, Marie-Ange; Glukhova, Marina A.; Stingl, John

    2014-01-01

    Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using 2 independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage tracing approach we follow the progeny of α-smooth muscle actin-expressing myoepithelial cells and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy. PMID:25173976

  6. Growth of human normal and neoplastic mammary tissues in the cleared mammary fat pad of the nude mouse.

    PubMed

    Outzen, H C; Custer, R P

    1975-12-01

    Dysplastic and malignant human breast tissues were grown successfully in the cleared mammary fat pads (CFP) of nude mice. The mammary fat pads were cleared while the mice were in a germfree isolator. Prepared mice were removed fron the germfree enviornment to facilitate transplantation of the human mammary tissue into their CFP and subsequently were maintained in sterile laminar flow racks.

  7. Characterization of Human Mammary Epithelial Stem Cells

    DTIC Science & Technology

    2009-10-01

    Appendix……………………………………………………………………………… 11 Eirew,P., Stingl,J., Raouf,A., Turashvili,G., Aparicio ,S., Emerman,J.T., and Eaves,C.J. A method for... Aparicio , Joanne Emerman and Connie Eaves. A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability...Abstracts Peter Eirew, John Stingl, Afshin Raouf, Gulisa Turshvili, Sam Aparicio , Joanne Emerman and Connie Eaves, “Identification of Human Mammary

  8. Symptomatic and incidental mammary duct ectasia.

    PubMed Central

    Browning, J; Bigrigg, A; Taylor, I

    1986-01-01

    The histology obtained from 1256 female patients undergoing breast surgery was reviewed. Mammary duct ectasia was noted in 51 (4.2%) patients who had associated symptoms and in 103 (8.1%) patients where duct ectasia was recognized as an incidental finding. The syndrome is defined by primary (nipple change or sepsis) and secondary (pain and lump) symptoms. Formal duct excision gives good results for symptomatic duct ectasia. It is postulated that many women have nonsymptomatic mammary duct ectasia. Secondary infection gives rise to nipple change, lump and pain. In the severe form abscess and fistula formation occurs which necessitates repeated surgical treatment, and rarely mastectomy. PMID:3806542

  9. Stromal Effects on Mammary Gland Development and Breast Cancer

    NASA Astrophysics Data System (ADS)

    Wiseman, Bryony S.; Werb, Zena

    2002-05-01

    Breast cancer manifests itself in the mammary epithelium, yet there is a growing recognition that mammary stromal cells also play an important role in tumorigenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer, and many of the stromal factors necessary for mammary development also promote or protect against breast cancer. Here we review our present knowledge of the specific factors and cell types that contribute to epithelial-stromal crosstalk during mammary development. To find cures for diseases like breast cancer that rely on epithelial-stromal crosstalk, we must understand how these different cell types communicate with each other.

  10. Tubulopapillary mammary carcinoma in a brown bear (Ursus arctos).

    PubMed

    Nak, Deniz; Cangul, I Taci; Nak, Yavuz; Cihan, Huseyin; Celimli, Nureddin

    2008-04-01

    A 28-yr-old, nulliparous female brown bear (Ursus arctos) at the Karacabey Ovakurusu Bear Sanctuary presented with an enlargement of the mammary gland. Three other nodules were also noted in the proximity of the mammary gland and over the vulva. Clinical, hematologic, ultrasonographic, and radiologic examinations were performed; the enlarged mammary gland was removed and the other masses were also excised. Histopathologic examination revealed tubulopapillary carcinoma of the mammary gland, and the other masses were diagnosed as epidermoid cysts. This is the first reported case of tubulopapillary mammary carcinoma accompanied by epidermoid cysts in a bear.

  11. Canine mammary tumour cell lines established in vitro.

    PubMed

    Hellmén, E

    1993-01-01

    Mammary tumours are the most common tumours in the female dog. The tumours have a complex histology and exist in epithelial, mixed and mesenchymal forms. To study the biology of canine mammary tumours, five cell lines have been established and characterized. The results indicate that canine mammary tumours might be derived from mammary stem cells and that the tumour growth is independent of oestrogens. The established canine mammary tumour cell lines will be valuable tools in further studies of the histogenesis and pathogenesis of these tumours.

  12. [Mammary ductal ectasia child. Diagnostic and therapeutic approach].

    PubMed

    Martínez-Medel, Jorge; Cabistany-Esqué, Ana Cristina; Sanz-Asin, Olga; del Martínez-Rubio, María Pilar; Echavarren-Plaza, Virginia; Arroyo-Lemarroy, Taydé

    2014-01-01

    Mammary duct ectasia in childhood is a rare disease. It appears typically as a periareolar mammary mass and/or nipple discharge. Even though in the adult age is an acquired disease, its occurrence in children suggests it may constitute a development mammary gland anomaly. Sonography is highly useful in the diagnosis. Differential diagnosis must include other nipple discharge and mammary mass causes as the juvenile fibroadenoma or malignant pathology. This usually is a self-limited process, so that a conservative approach is recommended, even though occasionally surgical treatment is required. We report the case of a 13 years old girl with nipple discharge who finally was diagnosed bilateral mammary duct ectasia.

  13. Positional variations in mammary gland development and cancer.

    PubMed

    Veltmaat, Jacqueline M; Ramsdell, Ann F; Sterneck, Esta

    2013-06-01

    Most mammals develop their mammary glands in pairs of which the two counterparts are symmetrically displaced away from the ventral midline. Based on this symmetry and the same functional outcome as a milk-producing organ, the mammary glands are easily presumed to be mere copies of one another. Based on our analysis of published data with inclusion of new results related to mammary development and pathology in mice, we argue that this presumption is incorrect: Between and within pairs, mammary glands differ from one another, and tumor incidence and biology depend on the position along the anterior-posterior and the left-right axis as well. This insight has implications for experimental designs with mouse models and for data extrapolation between mammary glands within and between species. We suggest that improved documentation of location-specific mammary gland features will lead to more insights into the molecular mechanisms of mammary gland development and cancer biology in both mice and humans.

  14. CLINICOPATHOLOGIC FEATURES OF MAMMARY MASSES IN CAPTIVE LIONS (PANTHERA LEO).

    PubMed

    Sadler, Ryan A; Craig, Linden E; Ramsay, Edward C; Helmick, Kelly; Collins, Darin; Garner, Michael M

    2016-03-01

    A multi-institutional retrospective analysis of 330 pathology accessions from 285 different lions found 15 captive, female African lions (Panthera leo) with confirmed mammary masses. Aside from the presence of a mammary mass, the most common initial clinical sign was inappetence. Histologic diagnoses were predominantly adenocarcinoma (n = 12), though two benign masses (mammary hyperplasia and a mammary cyst) and one squamous cell carcinoma were identified. Nine of 13 malignant tumors had metastasized to lymph nodes or viscera at the time of necropsy. Six lions with adenocarcinoma and two lions with benign mammary masses had received hormonal contraception, though little evidence of mammary lobular hyperplasia was seen in association with the adenocarcinomas. The most common concurrent disease processes found at necropsy were chronic urinary tract disease and other malignancies. These cases demonstrate that mammary malignancies occur in captive lions and frequently metastasize.

  15. Mouse Mammary Tumor Virus-Like Nucleotide Sequences in Canine and Feline Mammary Tumors▿

    PubMed Central

    Hsu, Wei-Li; Lin, Hsing-Yi; Chiou, Shyan-Song; Chang, Chao-Chin; Wang, Szu-Pong; Lin, Kuan-Hsun; Chulakasian, Songkhla; Wong, Min-Liang; Chang, Shih-Chieh

    2010-01-01

    Mouse mammary tumor virus (MMTV) has been speculated to be involved in human breast cancer. Companion animals, dogs, and cats with intimate human contacts may contribute to the transmission of MMTV between mouse and human. The aim of this study was to detect MMTV-like nucleotide sequences in canine and feline mammary tumors by nested PCR. Results showed that the presence of MMTV-like env and LTR sequences in canine malignant mammary tumors was 3.49% (3/86) and 18.60% (16/86), respectively. For feline malignant mammary tumors, the presence of both env and LTR sequences was found to be 22.22% (2/9). Nevertheless, the MMTV-like LTR and env sequences also were detected in normal mammary glands of dogs and cats. In comparisons of the MMTV-like DNA sequences of our findings to those of NIH 3T3 (MMTV-positive murine cell line) and human breast cancer cells, the sequence similarities ranged from 94 to 98%. Phylogenetic analysis revealed that intermixing among sequences identified from tissues of different hosts, i.e., mouse, dog, cat, and human, indicated the MMTV-like DNA existing in these hosts. Moreover, the env transcript was detected in 1 of the 19 MMTV-positive samples by reverse transcription-PCR. Taken together, our study provides evidence for the existence and expression of MMTV-like sequences in neoplastic and normal mammary glands of dogs and cats. PMID:20881168

  16. Mouse mammary tumor virus-like nucleotide sequences in canine and feline mammary tumors.

    PubMed

    Hsu, Wei-Li; Lin, Hsing-Yi; Chiou, Shyan-Song; Chang, Chao-Chin; Wang, Szu-Pong; Lin, Kuan-Hsun; Chulakasian, Songkhla; Wong, Min-Liang; Chang, Shih-Chieh

    2010-12-01

    Mouse mammary tumor virus (MMTV) has been speculated to be involved in human breast cancer. Companion animals, dogs, and cats with intimate human contacts may contribute to the transmission of MMTV between mouse and human. The aim of this study was to detect MMTV-like nucleotide sequences in canine and feline mammary tumors by nested PCR. Results showed that the presence of MMTV-like env and LTR sequences in canine malignant mammary tumors was 3.49% (3/86) and 18.60% (16/86), respectively. For feline malignant mammary tumors, the presence of both env and LTR sequences was found to be 22.22% (2/9). Nevertheless, the MMTV-like LTR and env sequences also were detected in normal mammary glands of dogs and cats. In comparisons of the MMTV-like DNA sequences of our findings to those of NIH 3T3 (MMTV-positive murine cell line) and human breast cancer cells, the sequence similarities ranged from 94 to 98%. Phylogenetic analysis revealed that intermixing among sequences identified from tissues of different hosts, i.e., mouse, dog, cat, and human, indicated the MMTV-like DNA existing in these hosts. Moreover, the env transcript was detected in 1 of the 19 MMTV-positive samples by reverse transcription-PCR. Taken together, our study provides evidence for the existence and expression of MMTV-like sequences in neoplastic and normal mammary glands of dogs and cats.

  17. Dietary genistein stimulates mammary development in gilts

    USDA-ARS?s Scientific Manuscript database

    The possible role of the phytoestrogen, genistein, on prepubertal development of mammary glands, hormonal status and bone resorption was investigated in gilts. Forty-five gilts were fed a control diet containing soya (CTLS, n = 15), a control diet without soya (CTL0, n = 15) or the CTLS diet supplem...

  18. Mammary Cancer and Activation of Transposable Elements

    DTIC Science & Technology

    2014-09-01

    AD_________________ AWARD NUMBER: W81XWH-11-1-0401 TITLE: Mammary Cancer and Activation of Transposable Elements PRINCIPAL INVESTIGATOR...way as transcripts from the regular gene promoter. Transcriptional activation of retrotransposons is strongly linked with their CpG DNA methylation

  19. Proteomic Analysis of Genistein Mammary Cancer Chemoprevention

    DTIC Science & Technology

    2007-07-01

    to collect a higher yield of proteins and hopefully allow success. 15. SUBJECT TERMS Genistein , Breast Cancer Chemoprevention, Proteomics, Rats ...AD_________________ Award Number: DAMD17-03-1-0433 TITLE: Proteomic Analysis of Genistein ...SUBTITLE 5a. CONTRACT NUMBER Proteomic Analysis of Genistein Mammary Cancer Chemoprevention 5b. GRANT NUMBER DAMD17-03-1-0433 5c. PROGRAM

  20. Mass spectrometry of ion-induced water clusters: an explanation of the infrared continuum absorption.

    PubMed

    Carlon, H R; Harden, C S

    1980-06-01

    Mass spectrometry was used to study ion-induced water clusters [H(+)(H(2)O)(c)], where c = the cluster size, i.e.,the number of monomers per cluster. It is shown that the numbers of hydrogen bonds in populations of these clusters in water vapor vary as the square of partial pressure and inversely with temperature, with functional dependencies that are almost identical to those observed for the infrared continuum absorption and for anomalous absorption in other wavelength regions. Experimental mass spectra taken at constant temperature vs partial pressure and data obtained at constant water vapor partial pressure vs temperature are presented and discussed. These results are combined with the evidence of cloud physicists including C. T. R. Wilson to show rather conclusively that naturally occurring ionic processes in water vapor generate large populations of hydrogen-bonded neutral water clusters that are responsible for the infrared continuum absorption. These processes can be enhanced by various kinds of ionizing energy, thus increasing anomalous absorption in water vapor or in moist air. If electrical properties of the atmosphere influence the infrared continuum absorption, which is an important mechanism in determining climate at the earth's surface, it will be necessary to reexamine extensively existing models of atmospheric radiative transfer.

  1. The use of low energy, ion induced nuclear reactions for proton radiotherapy applications

    NASA Astrophysics Data System (ADS)

    Horn, K. M.; Doyle, B.; Segal, M. N.; Hamm, R. W.; Adler, R. J.; Glatstein, E.

    1995-12-01

    Medical radiotherapy has traditionally relied upon the use of external photon beams and internally implanted radioisotopes as the chief means of irradiating tumors. However, advances in accelerator technology and the exploitation of novel means of producing radiation may provide useful alternatives to some current modes of medical radiation delivery — with reduced total dose to surrounding healthy tissue, reduced expense, or increased treatment accessibility. This paper will briefly overview currently established modes of radiation therapy, techniques still considered experimental but in clinical use and innovative concepts under study that may enable new forms of treatment or enhance existing ones. The potential role of low energy, ion-induced nuclear reactions in radiotherapy applications is examined specifically for the 650 keV d( 3He,p) 4 He nuclear reaction. This examination will describe the basic physics associated with this reaction's production of 17.4 MeV protons and the processes used to fabricate the necessary materials used in the technique. Calculations of the delivered radiation dose, heat generation, and required exposure times are presented. Experimental data is also presented validating the dose calculations. The design of small, lower cost ion accelerators, as embodied in "nested"-tandem and radio frequency quadrupole accelerators is examined, as is the potential use of high-output 3He and deuterium ion sources. Finally, potential clinical applications are discussed in terms of the advantages and disadvantages of this technique with respect to current radiotherapy methods and equipment.

  2. The use of low energy, ion induced nuclear reactions for proton radiotherapy applications

    NASA Astrophysics Data System (ADS)

    Doyle, B.; Hamm, R. W.; Adler, R. J.; Glatstein, E.; Horn, K. M.; Segal, M. N.

    1995-12-01

    Medical radiotherapy has traditionally relied upon the use of external photon beams and internally implanted radioisotopes as the chief means of irradiating tumors. However, advances in accelerator technology and the exploitation of novel means of producing radiation may provide useful alternatives to some current modes of medical radiation delivery - with reduced total dose to surrounding healthy tissue, reduced expense, or increased treatment accessibility. This paper will briefly overview currently established modes of radiation therapy, techniques still considered experimental but in clinical use and innovative concepts under study that may enable new forms of treatment or enhance existing ones. The potential role of low energy, ion-induced nuclear reactions in radiotherapy applications is examined specifically for the 650 keV d(3He,p)4He nuclear reaction. This examination will describe the basic physics associated with this reaction's production of 17.4 MeV protons and the processes used to fabricate the necessary materials used in the technique. Calculations of the delivered radiation dose, heat generation, and required exposure times are presented. Experimental data is also presented validating the dose calculations. The design of small, lower cost ion accelerators, as embodied in 'nested'-tandem and radio frequency quadrupole accelerators is examined, as is the potential use of high-output He3e and deuterium ion sources. Finally, potential clinical applications are discussed in terms of the advantages and disadvantages of this technique with respect to current radiotherapy methods and equipment.>

  3. Mechanisms of ion-induced GaN thin layer splitting

    NASA Astrophysics Data System (ADS)

    Moutanabbir, O.; Chabal, Y. J.; Chicoine, M.; Christiansen, S.; Krause-Rehberg, R.; Schiettekatte, F.; Scholz, R.; Seitz, O.; Senz, S.; Süßkraut, F.; Gösele, U.

    2009-05-01

    The underlying physics and the role of H-defect interaction in H ion-induced splitting of GaN were investigated by transmission electron microscopy, high resolution X-ray diffraction, positron annihilation spectroscopy, ion channeling, elastic recoil detection, and infrared spectroscopy. A high concentration of void-like nanoscopic structures, nanobubbles, is detected immediately after implantation. Positron annihilation measurements demonstrate that the detected structures are vacancy clusters. FTIR data show that H-defect vibrational spectrum peaks at 3141 cm-1 mode attributed to VGa-H4. A large fraction of H was found to be trapped in higher frequency modes which we associate tentatively to N-H stretch modes in the internal surfaces of nanobubbles. These nanobubbles persist during annealing up to 450 °C. An increase of the strain is observed in this temperature range. This strain relaxes partially above 450 °C following the formation of the platelets which are embryos of the microcracks.

  4. Track damage and erosion of insulators by ion-induced electronic processes

    NASA Technical Reports Server (NTRS)

    Tombrello, T. A.

    1984-01-01

    Track damage and the associated ejection of atoms and molecules from insulators, which occur as a result of ion-induced electronic excitation, are of interest both in their own right and because of the mechanisms through which the energy in the excited electrons is transformed into atomic motion. In this paper an overview is given of the phenomena that are observed. We show that there is a remarkable similarity between the damage profile along the ion's track in the solid and the yield of ejected atoms at the energy that corresponds to each point on the track. It is also seen that the density of extended defects (or, correspondingly, the ejected particle yield) appears to have a 'universal' form that is weakly dependent on the type of material. In the model presented this is a consequence of the inner-shell ionization of light elements in the solid by the incident ion; the resulting Auger decay produces an intense ionization spike that locally triggers the track formation/erosion process. This model allows the estimation of erosion yields/damage profiles for different ions and materials.

  5. Dissection of the ion-induced folding of the hammerhead ribozyme using 19F NMR

    PubMed Central

    Hammann, Christian; Norman, David G.; Lilley, David M. J.

    2001-01-01

    We have used 19F NMR to analyze the metal ion-induced folding of the hammerhead ribozyme by selective incorporation of 5fluorouridine. We have studied the chemical shift and linewidths of 19F resonances of 5-fluorouridine at the 4 and 7 positions in the ribozyme core as a function of added Mg2+. The data fit well to a simple two-state model whereby the formation of domain 1 is induced by the noncooperative binding of Mg2+ with an association constant in the range of 100 to 500 M−1, depending on the concentration of monovalent ions present. The results are in excellent agreement with data reporting on changes in the global shape of the ribozyme. However, the NMR experiments exploit reporters located in the center of the RNA sections undergoing the folding transitions, thereby allowing the assignment of specific nucleotides to the separate stages. The results define the folding pathway at high resolution and provide a time scale for the first transition in the millisecond range. PMID:11331743

  6. Is sputtering relevant for ion-induced self-organized pattern formation?

    NASA Astrophysics Data System (ADS)

    Hofsäss, Hans; Bobes, Omar; Zhang, Kun

    2013-04-01

    Recently it was reported that ion-induced mass redistribution rather than sputtering would solely determine ripple pattern formation of ion-irradiated surfaces. We investigate the pattern formation on Si irradiated with Xe ions with energies of 5 and 10 keV. Sputter yield and collision cascade characteristics vary strongly as function of ion energy, ion mass and substrate material and allow us to investigate the contributions of curvature dependent erosion as well as mass redistribution. The experimental results are compared with calculations of the curvature coefficients Sx and Sy. Parameters required for the calculations are extracted from Monte Carlo simulations with program SDTrimSP. The calculated curvature coefficients show that mass redistribution is dominant for parallel ripple formation in most cases. The angle where the pattern orientation changes from parallel to perpendicular ripples is however related to curvature dependent sputtering. We discuss the possibilities to tune the different contributions to pattern formation and examine the possibility to completely eliminate mass redistribution effects.

  7. Ferrous ion induced photon emission as a method to quantify oxidative stress in stored boar spermatozoa.

    PubMed

    Gogol, Piotr; Pieszka, Marek

    2008-01-01

    The aim of the study was to evaluate the effect of semen storage on ferrous ion induced luminescence of boar spermatozoa and to determine the relationship between parameters of this luminescence and lipid peroxidation as measured by malondialdehyde (MDA) contents. Boar semen samples were diluted in Biosolwens extender and stored for 12 days at 15 degrees C. Luminescence and MDA were measured directly after dilution (day 0) and at 6 and 12 days of semen storage. Luminescence was measured at 20 degrees C using a luminometer equipped with a cooled photomultiplier with a spectral response range from 370 to 620 nm. Emission was induced by adding FeSO4 solution (final concentration 0.05 mM). MDA content was measured by the HPLC method. The day of storage had a significant effect on some luminescence parameters and MDA content in spermatozoa. A significant correlation was observed between luminescence parameters and MDA concentration. The results of the study confirm that induced luminescence is strictly related to lipid peroxidation in spermatozoa that occur during boar semen storage. Parameters of luminescence treated as a holistic response of cells to oxidative stress can be useful for monitoring spermatozoa quality during semen preservation.

  8. Metal ion-induced lateral aggregation of filamentous viruses fd and M13.

    PubMed Central

    Tang, Jay X; Janmey, Paul A; Lyubartsev, Alexander; Nordenskiöld, Lars

    2002-01-01

    We report a detailed comparison between calculations of inter-filament interactions based on Monte-Carlo simulations and experimental features of lateral aggregation of bacteriophages fd and M13 induced by a number of divalent metal ions. The general findings are consistent with the polyelectrolyte nature of the virus filaments and confirm that the solution electrostatics account for most of the experimental features observed. One particularly interesting discovery is resolubilization for bundles of either fd or M13 viruses when the concentration of the bundle-inducing metal ion Mg(2+) or Ca(2+) is increased to large (>100 mM) values. In the range of Mg(2+) or Ca(2+) concentrations where large bundles of the virus filaments are formed, the optimal attractive interaction energy between the virus filaments is estimated to be on the order of 0.01 kT per net charge on the virus surface when a recent analytical prediction to the experimentally defined conditions of resolubilization is applied. We also observed qualitatively distinct behavior between the alkali-earth metal ions and the divalent transition metal ions in their action on the charged viruses. The understanding of metal ions-induced reversible aggregation based on solution electrostatics may lead to potential applications in molecular biology and medicine. PMID:12080143

  9. Ions-induced nanostructuration: effect of specific ionic adsorption on hydrophobic polymer surfaces.

    PubMed

    Siretanu, Igor; Chapel, Jean-Paul; Bastos-González, Delfi; Drummond, Carlos

    2013-06-06

    The effect of surface charges on the ionic distribution in close proximity to an interface has been extensively studied. On the contrary, the influence of ions (from dissolved salts) on deformable interfaces has been barely investigated. Ions can adsorb from aqueous solutions on hydrophobic surfaces, generating forces that can induce long-lasting deformation of glassy polymer films, a process called ion-induced polymer nanostructuration, IPN. We have found that this process is ion-specific; larger surface modifications are observed in the presence of water ions and hydrophobic and amphiphilic ions. Surface structuration is also observed in the presence of certain salts of lithium. We have used streaming potential and atomic force microscopy to study the effect of dissolved ions on the surface properties of polystyrene films, finding a good correlation between ionic adsorption and IPN. Our results also suggest that the presence of strongly hydrated lithium promotes the interaction of anions with polystyrene surfaces and more generally with hydrophobic polymer surfaces, triggering then the IPN process.

  10. Ion-induced folding of the hammerhead ribozyme: a fluorescence resonance energy transfer study.

    PubMed Central

    Bassi, G S; Murchie, A I; Walter, F; Clegg, R M; Lilley, D M

    1997-01-01

    The ion-induced folding transitions of the hammerhead ribozyme have been analysed by fluorescence resonance energy transfer. The hammerhead ribozyme may be regarded as a special example of a three-way RNA junction, the global structure of which has been studied by comparing the distances (as energy transfer efficiencies) between the ends of pairs of labelled arms for the three possible end-to-end vectors as a function of magnesium ion concentration. The data support two sequential ion-dependent transitions, which can be interpreted in the light of the crystal structures of the hammerhead ribozyme. The first transition corresponds to the formation of a coaxial stacking between helices II and III; the data can be fully explained by a model in which the transition is induced by a single magnesium ion which binds with an apparent association constant of 8000-10 000 M-1. The second structural transition corresponds to the formation of the catalytic domain of the ribozyme, induced by a single magnesium ion with an apparent association constant of approximately 1100 M-1. The hammerhead ribozyme provides a well-defined example of ion-dependent folding in RNA. PMID:9405376

  11. Mass Spectrometric Study on Sodium Ion Induced Central Nucleotide Deletion in the Gas Phase

    NASA Astrophysics Data System (ADS)

    Flosadóttir, Helga Dögg; Gíslason, Kristmann; Sigurdsson, Snorri Thor; Ingólfsson, Oddur

    2012-04-01

    We report a mass spectrometric study on sodium ion induced central nucleotide deletion from protonated oligonucleotides (ONTs) and the concurrent recombination of the terminal nucleotides. To shed some light on the mechanism behind this intriguing fragmentation channel, we have studied the metastable decay of a number of different protonated hexameric and octameric oligonucleotides with 0-6 and 0-8 of their exchangeable protons replaced with sodium ions, respectively. In selected cases, we have also studied the further fragmentation of the parent ions after initial base loss. Our findings are concurrent with a reaction mechanism where the initial step is the elimination of a protonated, high proton affinity (PA) base from the center of the ONTs. This is followed by an elimination of a (next neighbour) nucleotide that contains a second high PA base and the concurrent recombination of the terminal nucleotides. To our knowledge, such central nucleotide deletion in the gas phase has only been reported in one previous study (Flosadóttir et al., J. Am. Soc. Mass Spectrom 20:689-696, 2009), and this is the first systematic approach to understand the mechanism behind this channel.

  12. Sign preference in ion-induced nucleation: contributions to the free energy barrier.

    PubMed

    Keasler, Samuel J; Kim, Hyunmi; Chen, Bin

    2012-11-07

    We have performed a series of computer simulations using the AVUS-HR approach to better understand the origin of the sign preference in ion-induced nucleation. In particular, we emphasize the importance of distinguishing between the total formation free energy of a cluster, and the nucleation free energy, which involves only those steps contributing to the free energy barrier. We have separately considered how the ion-water potential energy, the water-water potential energy, and the entropy contribute to both the cluster formation free energy, and the nucleation free energy. These simulations have shown that while the ion-water potential energies make the largest contribution to the formation free energy difference between positive and negative ions, the entropy is the contribution leading to lower nucleation free energy barriers for negative ions. The primary reason for this is the larger stable (but precritical) clusters formed around negative ions. We have further shown that the distinction between formation and nucleation free energies is of particular importance when comparing small cations with larger anions where the formation free energies can be much lower for the cationic clusters, even though the nucleation barriers are lower for the anionic clusters.

  13. Ion induced stress relaxation in dense sputter-deposited DLC thin films

    NASA Astrophysics Data System (ADS)

    Aijaz, Asim; Kubart, Tomas

    2017-07-01

    Deposition of high-density and low-stress hydrogen-free diamond like carbon (DLC) thin films is demonstrated using a pulsed ionized sputtering process. This process is based on high power impulse magnetron sputtering, and high C ionization is achieved using Ne as the sputtering gas. The intrinsic compressive stress and its evolution with respect to ion energy and ion flux are explained in terms of the compressive stress based subplantation model for DLC growth by Davis. The highest mass density was ˜2.7 g/cm3, and the compressive stresses did not exceed ˜2.5 GPa. The resulting film stresses are substantially lower than those achieved for the films exhibiting similar mass densities grown by filtered cathodic vacuum arc and pulsed laser deposition methods. This unique combination of high mass density and low compressive stress is attributed to the ion induced stress relaxation during the pulse-off time which corresponds to the post thermal spike relaxation timescales. We therefore propose that the temporal ion flux variations determine the magnitude of the compressive stress observed in our films.

  14. The use of low energy, ion induced nuclear reactions for proton radiotherapy applications

    SciTech Connect

    Horn, K.M.; Doyle, B.; Segal, M.N.; Hamm, R.W.; Adler, R.J.; Glatstein, E.

    1995-04-01

    Medical radiotherapy has traditionally relied upon the use of external photon beams and internally implanted radioisotopes as the chief means of irradiating tumors. However, advances in accelerator technology and the exploitation of novel means of producing radiation may provide useful alternatives to some current modes of medical radiation delivery with reduced total dose to surrounding healthy tissue, reduced expense, or increased treatment accessibility. This paper will briefly overview currently established modes of radiation therapy, techniques still considered experimental but in clinical use, innovative concepts under study that may enable new forms of treatment or enhance existing ones. The potential role of low energy, ion-induced nuclear reactions in radiotherapy applications is examined specifically for the 650 keV d({sup 3}He,p){sup 4}He nuclear reaction. This examination will describe the basic physics associated with this reaction`s production of 17.4 MeV protons and the processes used to fabricate the necessary materials used in the technique. Calculations of the delivered radiation dose, heat generation, and required exposure times are presented. Experimental data are also presented validating the dose calculations. The design of small, lower cost ion accelerators, as embodied in `nested`-tandem and radio frequency quadrupole accelerators is examined, as is the potential use of high-output {sup 3}He and deuterium ion sources. Finally, potential clinical applications are discussed in terms of the advantages and disadvantages of this technique with respect to current radiotherapy methods and equipment.

  15. Molecular cytogenetic characterization of mammary neuroendocrine carcinoma.

    PubMed

    Xiang, De-Bing; Wei, Bing; Abraham, Susan C; Huo, Lei; Albarracin, Constance T; Zhang, Hong; Babiera, Gildy; Caudle, Abigail S; Akay, Catherine L; Rao, Pulivarthi; Zhao, Yi-Jue; Lu, Xinyan; Wu, Yun

    2014-09-01

    Primary mammary neuroendocrine carcinoma (NEC) is an uncommon entity that accounts for 2% to 5% of breast carcinomas. Recent reports have shown that NEC of the breast is an aggressive subtype of mammary carcinoma that is distinct from invasive ductal carcinoma, not otherwise specified, and have suggested that these tumors have a poorer prognosis than invasive ductal carcinoma, not otherwise specified. In this study, we provide the first cytogenetic characterization of mammary NEC using both conventional G-banding and spectral karyotype on a group of 7 tumors. We identified clonal chromosomal aberrations in 5 (71.4%) cases, with 4 of them showing complex karyotypes. Of these, recurrent numerical aberrations included gain of chromosome 7 (n = 2) and loss of chromosome 15 (n = 2). Recurrent clonal structural chromosomal aberrations involved chromosomes 1 (n = 3), 3 (n = 2), 6q (n = 3), and 17q (n = 3). Of the 4 (57.1%) cases with complex karyotypes, 2 showed evidence of chromothripsis, a phenomenon in which tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. One of these had evidence of chromothripsis involving chromosomes 1, 6, 8, and 15. The other also had evidence of chromosome 8 chromothripsis, making this a recurrent finding shared by both cases. We also found that mammary NEC shared some cytogenetic abnormalities--such as trisomy 7 and 12--with other neuroendocrine tumors in the lung and gastrointestinal tract, suggesting trisomy 7 and 12 as potential common molecular aberrations in neuroendocrine tumors. To our knowledge, this is the first report on molecular cytogenetic characterization of mammary NEC.

  16. Quantification of VEGF-C expression in canine mammary tumours.

    PubMed

    Qiu, C; Lin, D D; Wang, H H; Qiao, C H; Wang, J; Zhang, T

    2008-07-01

    Tumours release angiogenic factors such as vascular endothelium growth factor (VEGF), which induces growth of a capillary network around the tumour. Elevated concentrations of VEGF have been reported in human mammary gland tumours. To evaluate the expression of VEGF-C mRNA in canine mammary tissue, 38 mammary gland tumours (including 15 benign and 23 malignant mammary tumours), and 4 normal mammary glands were investigated by real-time reverse transcriptase quantitative polymerase chain reaction. VEGF-C expression in the malignant mammary tumours was much higher than in the benign mammary tumours or normal mammary tissue (P < 0.001). The expression of VEGF-C in tumours with lymph node metastasis was much higher than in those without (P < 0.01). The level of expression of VEGF-C did not correlate with tumour size or the patient's age, but was significantly higher in malignant mammary tumours and related to lymph node metastasis, making it a candidate marker for predicting metastasis of canine mammary cancer.

  17. CDP Is a Repressor of Mouse Mammary Tumor Virus Expression in the Mammary Gland

    PubMed Central

    Zhu, Quan; Gregg, Keqin; Lozano, Mary; Liu, Jinqi; Dudley, Jaquelin P.

    2000-01-01

    Mouse mammary tumor virus (MMTV) transcription is highest in the lactating mammary gland but is detectable in a variety of other tissues. Previous results have shown that MMTV expression is suppressed in lymphoid and other tissues through the binding of the homeodomain-containing repressor special AT-rich binding protein 1 to a negative regulatory element (NRE) in the MMTV long terminal repeat (LTR). Another homeoprotein repressor, CCAAT displacement protein (CDP), also binds to the MMTV NRE, but a role for CDP in MMTV transcriptional suppression has not yet been demonstrated. In this paper, we show that the level of CDP decreases during development of the mammary gland and that this decline in CDP level correlates with the known increase in MMTV expression observed during mammary gland differentiation. Moreover, CDP overexpression was able to suppress MMTV LTR-reporter gene activity up to 20-fold in transient-transfection assays of mouse mammary cells. To determine if this effect was due to direct binding of CDP to the promoter-proximal NRE, we performed DNase I protection assays to map two CDP-binding sites from +835 to +845 and +920 to +931 relative to the first base of the LTR. Mutations engineered into each of these sites decreased CDP binding to the proximal NRE, whereas a combination of these mutations further reduced binding. Subsequently, each of these mutations was introduced into the full-length MMTV LTR upstream of the luciferase reporter gene. Analysis of stable transfectants of LTR constructs showed that CDP binding site mutations in the proximal NRE elevated reporter gene expression two- to sixfold compared to wild-type LTR constructs. Thus, MMTV expression increases during mammary gland development, in part due to decreased CDP levels and CDP binding to the LTR. Together, these experiments provide the first evidence that CDP acts as a repressor of MMTV transcription in the mammary gland. PMID:10864645

  18. Heavy Flavors

    NASA Astrophysics Data System (ADS)

    Cox, B.; Soni, A.

    This is a summary report of the working group on Heavy Flavors. Discussions at the workshop were centered on B physics and on the signals for heavy quarks and leptons at the SSC. The Working Group Members were: V. Barger, H.-U. Bengtsson, C. Buchanan, I. Bigi, M. Block, B. Cox, N. Glover, J. Hewett, W.Y. Keung, B. Margolis, T. Rizzo, M. Suzuki, A. Soni, D. Stork, and S. Willenbrock.

  19. Considerations for application of Si(Li) detectors in analyses of sub-keV, ion-induced x rays

    SciTech Connect

    Musket, R.G.

    1985-06-19

    Spectroscopy of ion-induced x rays is commonly performed using lithium-drifted, silicon detectors, Si(Li), with beryllium windows. Strong absorption of x rays with energies below 1 keV occurs in even the thinnest commercially available beryllium windows and precludes useful analysis of sub-keV x rays. Access to the sub-keV x ray region can be achieved using windowless (WL) and ultra-thin-windowed (UTW) Si(Li) detectors. These detectors have been shown to be useful for spectroscopy of x rays with energies above approximately 200 eV. The properties of such detectors are reviewed with regard to analysis of ion-induced x rays. In particular, considerations of detection efficiency, output linearity, energy resolution, peak shapes, and vacuum requirements are presented. The use of ion excitation for determination of many detector properties serves to demonstrate the usefulness of WL and UTW detectors for the spectroscopy of sub-keV, ion-induced x rays. 23 refs., 4 figs.

  20. Nanodosimetric Simulation of Direct Ion-Induced DNA Damage Using Different Chromatin Geometry Models.

    PubMed

    Henthorn, N T; Warmenhoven, J W; Sotiropoulos, M; Mackay, R I; Kirkby, K J; Merchant, M J

    2017-08-09

    Monte Carlo based simulation has proven useful in investigating the effect of proton-induced DNA damage and the processes through which this damage occurs. Clustering of ionizations within a small volume can be related to DNA damage through the principles of nanodosimetry. For simulation, it is standard to construct a small volume of water and determine spatial clusters. More recently, realistic DNA geometries have been used, tracking energy depositions within DNA backbone volumes. Traditionally a chromatin fiber is built within the simulation and identically replicated throughout a cell nucleus, representing the cell in interphase. However, the in vivo geometry of the chromatin fiber is still unknown within the literature, with many proposed models. In this work, the Geant4-DNA toolkit was used to build three chromatin models: the solenoid, zig-zag and cross-linked geometries. All fibers were built to the same chromatin density of 4.2 nucleosomes/11 nm. The fibers were then LET proton irradiated (5-80 keV/μm) or LET alpha-particle irradiated (63-226 keV/μm). Nanodosimetric parameters were scored for each fiber after each LET and used as a comparator among the models. Statistically significant differences were observed in the double-strand break backbone size distributions among the models, although nonsignificant differences were noted among the nanodosimetric parameters. From the data presented in this article, we conclude that selection of the solenoid, zig-zag or cross-linked chromatin model does not significantly affect the calculated nanodosimetric parameters. This allows for a simulation-based cell model to make use of any of these chromatin models for the scoring of direct ion-induced DNA damage.

  1. Nitrite ion-induced fluorescence quenching of luminescent BSA-Au(25) nanoclusters: mechanism and application.

    PubMed

    Unnikrishnan, Binesh; Wei, Shih-Chun; Chiu, Wei-Jane; Cang, Jinshun; Hsu, Pang-Hung; Huang, Chih-Ching

    2014-05-07

    Fluorescence quenching is an interesting phenomenon which is highly useful in developing fluorescence based sensors. A thorough understanding of the fluorescence quenching mechanism is essential to develop efficient sensors. In this work, we investigate different aspects governing the nitrite ion-induced fluorescence quenching of luminescent bovine serum albumin stabilized gold nanoclusters (BSA-Au NCs) and their application for detection of nitrite in urine. The probable events leading to photoluminescence (PL) quenching by nitrite ions were discussed on the basis of the results obtained from ultraviolet-visible (UV-Vis) absorption spectroscopy, X-ray photoelectron spectroscopy (XPS), fluorescence measurements, circular dichroism (CD) spectroscopy, zeta potential and dynamic light scattering (DLS) studies. These studies suggested that PL quenching mainly occurred through the oxidation of Au(0) atoms to Au(i) atoms in the core of BSA-Au NCs mediated by nitrite ions. The interference caused by certain species such as Hg(2+), Cu(2+), CN(-), S(2-), glutathione, cysteine, etc. during the nitrite determination by fluorescence quenching was eliminated by using masking agents and optimising the conditions. Based on these findings we proposed a BSA-Au NC-modified membrane based sensor which would be more convenient for the real life applications such as nitrite detection in urine samples. The BSA-Au NC-modified nitrocellulose membrane (NCM) enabled the detection of nitrite at a level as low as 100 nM in aqueous solutions. This Au NC-based paper probe was validated to exhibit good performance for nitrite analysis in environmental water and urine samples, which makes it useful in practical applications.

  2. H+ ion-induced damage and etching of multilayer graphene in H2 plasmas

    NASA Astrophysics Data System (ADS)

    Davydova, A.; Despiau-Pujo, E.; Cunge, G.; Graves, D. B.

    2017-04-01

    H+ ion-induced damage of multilayer graphene (MLG) is investigated using Molecular Dynamics simulations as H2 plasmas could provide a possible route to pattern graphene. Low-energy (5-25 eV) H+ cumulative bombardment of ABA-stacked MLG samples shows an increase of the hydrogenation rate with the ion dose and ion energy. At 5 eV, the H coverage grows with the ion fluence only on the upper-side of the top layer but saturates around 35%. Hydrogenation of multi-layers and carbon etching are observed at higher energies. Layer-by-layer peeling/erosion of the MLG sample is observed at 10 eV and occurs in two phases: the MLG sample is first hydrogenated before carbon etching starts via the formation of CHx (˜60%) and C2Hx (˜30%) by-products. A steady state is reached after an ion dose of ˜5 × 1016 H+/cm2, as evidenced by a constant C etch yield (˜0.02 C/ion) and the saturation of the hydrogenation rate. At 25 eV, an original etching mechanism—lifting-off the entire top layer—is observed at low fluences due to the accumulation of H2 gas in the interlayer space and the absence of holes/vacancies in the top layer. However, as the underneath layers contain more defects and holes, this Smartcut-like mechanism cannot be not repeated and regular ion-assisted chemical etching is observed at higher fluences, with a yield of ˜0.05 C/ion.

  3. The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development

    NASA Astrophysics Data System (ADS)

    Finke, Daniela; Luther, Sanjiv A.; Acha-Orbea, Hans

    2003-01-01

    Mouse mammary tumor virus (MMTV) infection establishes chronic germinal centers and a lifelong neutralizing Ab response. We show that removal of the draining lymph node after establishment of the germinal center reaction led to complete loss of neutralizing Abs despite comparable infection levels in peripheral lymphocytes. Importantly, in the absence of neutralization, only the exocrine organs mammary gland, salivary gland, pancreas, and skin showed strikingly increased infection, resulting in accelerated mammary tumor development. Induction of stronger neutralization did not influence chronic infection levels of peripheral lymphoid organs but strongly inhibited mammary gland infection and virus transmission to the next generation. Taken together, we provide evidence that a tight equilibrium in virus neutralization allows limited infection of exocrine organs and controls cancer development in susceptible mouse strains. These experiments show that a strong neutralizing Ab response induced after infection is not able to control lymphoid MMTV infection. Strong neutralization, however, is capable of blocking amplification of mammary gland infection, tumor development, and virus transmission to the next generation. The results also indicate a role of neutralization in natural resistance to MMTV infection.

  4. Mouse mammary tumor virus suppresses apoptosis of mammary epithelial cells through ITAM-mediated signaling.

    PubMed

    Kim, Hyoung H; Grande, Shannon M; Monroe, John G; Ross, Susan R

    2012-12-01

    Many receptors in hematopoietic cells use a common signaling pathway that relies on a highly conserved immunoreceptor tyrosine-based activation motif (ITAM), which signals through Src family tyrosine kinases. ITAM-bearing proteins are also found in many oncogenic viruses, including the mouse mammary tumor virus (MMTV) envelope (Env). We previously showed that MMTV Env expression transformed normal mammary epithelial cells and that Src kinases were important mediators in this transformation. To study how ITAM signaling affects mammary cell transformation, we utilized mammary cell lines expressing two different ITAM-containing proteins, one encoding a MMTV provirus and the other a B cell receptor fusion protein. ITAM-expressing cells were resistant to both serum starvation- and chemotherapeutic drug-induced apoptosis, whereas cells transduced with these molecules bearing ITAM mutations were indistinguishable from untransduced cells in their sensitivity to these treatments. We also found that Src kinase was activated in the MMTV-expressing cells and that MMTV-induced apoptosis resistance was completely restored by the Src inhibitor PP2. In vivo, MMTV infection delayed involution-induced apoptosis in the mouse mammary gland. Our results show that MMTV suppresses apoptosis through ITAM-mediated Src tyrosine kinase signaling. These studies could lead to the development of effective treatment of nonhematopoietic cell cancers in which ITAM-mediated signaling plays a role.

  5. Heavy Ion Microbeam- and Broadbeam-Induced Transients in SiGe HBTs

    NASA Technical Reports Server (NTRS)

    Pellish, Jonathan A.; Reed, Robert A.; McMorrow, Dale; Vizkelethy, Gyorgy; Ferlet-Cavrois, Veronique; Baggio, Jacques; Duhamel, Olivier; Moen, Kurt A.; Phillips, Stanley D.; Diestelhorst, Ryan M.; hide

    2009-01-01

    SiGe HBT heavy ion-induced current transients are measured using Sandia National Laboratories microbeam and high- and low-energy broadbeam sources at the Grand Accelerateur National d'Ions Lourds and the University of Jyvaskyla. The data were captured using a custom broadband IC package and real-time digital phosphor oscilloscopes with at least 16 GHz of analog bandwidth. These data provide detailed insight into the effects of ion strike location, range, and LET.

  6. USF-1 as an Inhibitor of Mammary Gland Carcinogenesis

    DTIC Science & Technology

    2001-09-01

    The hypothesis tested in this proposal is that overexpression of USF in the mammary glands of transgenic mice will inhibit myc-dependent...tumorigenesis. To test this hypothesis, a transgene was constructed to target the overexpression of FLAG-tagged USF-2 to the mammary glands of transgenic mice ...under the control of the mouse mammary tumor virus (mmtv) long terminal repeat. A total of eight lines of transgenic mice were generated. Of these, one

  7. Genetic Susceptibility to Estrogen-Induced Mammary Cancers

    DTIC Science & Technology

    2000-11-01

    mammary glands were reflected in mammary histology. (A and E) Thin sections from Fig. 3. E2 induced pituitary growth and hyperprolactinemia similarly in...with E2 5 (33%) exhibited a normal DNA profile where the great for 12 wk induced pituitary growth and hyperprolactinemia in majority of cells displayed...etal. , " terone, or PRL. Hyperprolactinemia has been shown to be sufficient to induce mammary cancer in certain strains of mouse 1 , (29-31) and rat

  8. Radiologic and histologic presentation of male mammary myofibroblastoma.

    PubMed

    Omar, Lena A; Rojanapremsuk, Theera; Saluja, Karan; Merchant, Kanwal A; Sharma, Pooja B

    2016-07-01

    Mammary myofibroblastoma is a rare mesenchymal neoplasm that typically presents in older men and women. Less commonly, these benign tumors may also occur in soft tissues located outside of the breast, in which case they are referred to as mammary-type myofibroblastomas. The histologic composition of this benign spindle cell tumor can be markedly varied. We present a case of a large mammary myofibroblastoma in a male patient and discuss the typical imaging and histologic makeup of these tumors.

  9. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types

    NASA Technical Reports Server (NTRS)

    Wu, Honglu; Lu, Tao; Yeshitla, Samrawit; Zhang, Ye; Kadhim, Munira

    2016-01-01

    An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. To investigate GI induced by charged particles, we exposed human lymphocytes, human fibroblast cells, and human mammary epithelial cells to high energy protons and Fe ions. In addition, we also investigated GI in bone marrow cells isolated from CBA/CaH (CBA) and C57BL/6 (C57) mice, by analyzing cell survival and chromosome aberrations in the cells after multiple cell divisions. Results analyzed so far from the experiments indicated different sensitivities to charged particles between CBA/CaH (CBA) and C57BL/6 (C57) mouse strains, suggesting that there are two main types of response to irradiation: 1) responses associated with survival of damaged cells and 2) responses associated with the induction of non-clonal chromosomal instability in the surviving progeny of stem cells. Previously, we reported that the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions. Our results with different cell types demonstrated different RBE values between different cell types and between early and late chromosomal damages. This study also attempts to offer an explanation for the varying RBE values for different cancer types.

  10. Cytokine signalling in mammary gland development.

    PubMed

    Watson, Christine J; Oliver, Carrie H; Khaled, Walid T

    2011-03-01

    Mammary gland development occurs in three distinct stages during the lifetime of the female mammal: in embryonic, pubertal and reproductive life. At each of these developmental stages, different signalling molecules induce changes in both the epithelium and the surrounding stroma. However, it is during pregnancy that the most dramatic changes occur, resulting in a massive increase in the number of epithelial cells and in their function. Pregnancy initiates the development of a new epithelial lineage, the alveolar cells, which form the milk-producing lobuloalveolar structures. These cells become redundant at the end of lactation and are removed in an exquisitely controlled process of tissue remodelling coupled with extensive cell death. All of these events require not only steroid hormones but also sequential signalling by cytokines. A recent surprising discovery was that the signalling pathways and cytokines that regulate lineage determination in T helper cells are also involved in mammary gland development during pregnancy.

  11. Atherosclerosis and the internal mammary arteries

    SciTech Connect

    Singh, R.N.

    1983-06-01

    One hundred and fifty patients with coronary artery disease (CAD), 14 (9.3%) of whom had coexisting peripheral vascular disease, underwent bilateral internal mammary arteriography to study the incidence and extent of atherosclerosis in these vessels. Significant atherosclerosis of the internal mammary arteries (IMAs) was present in three patients (2%), of whom one had coexisting peripheral vascular disease. Lesions in the IMAs were found either proximally, close to the origin or distally, around the terminal bifurcation. Six of the 14 patients with peripheral vascular disease (4% of total subjects) had significant atherosclerosis of the brachiocephalic arteries. Atherosclerotic involvement of the IMA is very unusual and rarely interferes with the use of these vessels for coronary bypass. More common, however, is atherosclerosis of the subclavian arteries, a contraindication for IMA grafting if the lesion is proximal to the IMA origin.

  12. Apples prevent mammary tumors in rats.

    PubMed

    Liu, Rui Hai; Liu, Jiaren; Chen, Bingqing

    2005-03-23

    Regular consumption of fruits and vegetables has been consistently shown to be associated with reduced risk of developing chronic diseases such as cancer and cardiovascular disease. Apples are commonly consumed and are the major contributors of phytochemicals in human diets. It was previously reported that apple extracts exhibit strong antioxidant and antiproliferative activities and that the major part of total antioxidant activity is from the combination of phytochemicals. Phytochemicals, including phenolics and flavonoids, are suggested to be the bioactive compounds contributing to the health benefits of apples. Here it is shown that whole apple extracts prevent mammary cancer in a rat model in a dose-dependent manner at doses comparable to human consumption of one, three, and six apples a day. This study demonstrated that whole apple extracts effectively inhibited mammary cancer growth in the rat model; thus, consumption of apples may be an effective strategy for cancer protection.

  13. The evolving role of mammary ductoscopy.

    PubMed

    Mokbel, Kefah; Elkak, Abd Elrafea

    2002-01-01

    Mammary ductoscopy (MD) is an emerging technique that allows direct visualisation of the mammary duct system, and that produces sharp and clear video images and ductal washings for cytological analysis. There is a growing body of evidence that MD may have a role in the management of women with pathological nipple discharge, the guiding of breast conserving surgery for cancer, and the screening of high risk women. Further research is required to confirm these potential applications and the feasibility of its use in the rapid intervention and outpatient setting under local anaesthesia. Furthermore, the addition of molecular and genetic analysis of cells obtained by MD and the emergence of newer generations of microendoscopes are likely to enhance the use of this technique.

  14. Bovine mammary stem cells: new perspective for dairy science.

    PubMed

    Martignani, E; Cravero, D; Miretti, S; Accornero, P; Baratta, M

    2014-01-01

    Mammary stem cells provide opportunities for the cyclic remodelling of the bovine mammary gland. Therefore, understanding the character and regulation of mammary stem cells is important for increasing animal health and productivity. The exciting possibility that stem cell expansion can influence milk production is currently being investigated by several researchers. In fact, appropriate regulation of mammary stem cells could hopefully benefit milk yield, persistency of lactation, dry period management and tissue repair. Accordingly, we and others have attempted to characterize and regulate the function of bovine mammary stem cells. However, research on mammary stem cells requires tissue biopsies, which represents a limitation for the management of animal welfare. Interestingly, different studies recently reported the identification of putative mammary stem cells in human breast milk. The possible identification of primitive cell types within cow's milk may provide a non-invasive source of relevant mammary cells for a wide range of applications. In this review, we have summarized the main achievements in this field for dairy cow science and described the interesting perspectives open to manipulate milk persistency during lactation and to cope with oxidative stress during the transition period by regulating mammary stem cells.

  15. Growth requirements of human mammary epithelial cells in culture.

    PubMed

    Taylor-Papadimitriou, J; Shearer, M; Stoker, M G

    1977-12-15

    Colony-forming epithelial cells can be separated from the non-dividing "foam cells" in human milk by differential adhesion to glass and freezing. The growth of such partially purified mammary epithelial cells is stimulated by co-culture with non-dividing feeder cells. Foam cells, mitomycin-treated mouse fibroblast lines and human mammary fibroblasts and calf lens epithelial cells are all effective in promoting mammary epithelial cell growth. Contact between epithelial cells and feeders is not required for the growth-promoting effect. The mitogenic effect of epidermal growth factor on mammary epithelial cells also requires feeder cell activity.

  16. Metallothionein expression in benign and malignant canine mammary gland tumours.

    PubMed

    Erginsoy, S D; Sozmen, M; Caldin, M; Furlanello, T

    2006-08-01

    The presence of metallothioneins (MTs) were demonstrated immunohistochemically using a monoclonal antibody (E9) against a conserved epitope of I and II isoforms in canine mammary tumours. In a semiquantitative analysis MT expression in the tumour cells was observed in 54/54 cases of benign and 32/40 malignant mammary neoplasms. A statistically significant difference at the level of P<0.01 was observed for MT expression between benign and malign mammary tumours in terms of immunoreactivity score. It is concluded that immunohistochemically demonstrated MT expression is significantly associated with benign canine mammary tumours.

  17. Feline Mammary Carcinoma: A Retrospective Evaluation of 17 Cases

    PubMed Central

    Tomlinson, M. J.; Barteaux, L.; Ferns, L. E.; Angelopoulos, E.

    1984-01-01

    Seventeen biopsies of feline mammary carcinoma submitted to the Veterinary Pathology Laboratory, Nova Scotia Department of Agriculture and Marketing were reviewed. All 17 cases were female cats. Data on age, reproductive status (sexually intact vs. neutered), therapy, outcome of the cases and histological features were consistent with data on feline mammary carcinoma previously reported. Four of these 17 cats had a history of receiving exogenous progestin prior to tumor development. The possible role of progestins as initiators or promoters of feline mammary carcinoma was discussed. The use of feline mammary carcinoma as a model for carcinoma of the breast in women was reviewed. ImagesFigure 1. PMID:17422482

  18. Inbreeding and canine mammary cancer: a retrospective study.

    PubMed

    Dorn, C R; Schneider, R

    1976-09-01

    Using files of the Animal Neoplasm Registry (ANR) in Alameda and Contra Costa Counties, California, we conducted a retrospective study to compare the degree of inbreeding in the ancestry of purebred dogs with mammary and other cancers, and of those without tumors. Wright's coefficients of inbreeding, calculated for all animals in the three groups, ranged from 0.000 to 0.535. The median inbreeding coefficients of the mammary cancer and comparison groups (consisting of other cancers) were approximately twice that of the nonneoplastic group, but neither difference was statistically significant. Dogs with mammary adenocarcinoma and mixed mammary cancer had similar degrees of inbreeding.

  19. Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis.

    PubMed

    Visvader, Jane E

    2009-11-15

    The epithelium of the mammary gland exists in a highly dynamic state, undergoing dramatic morphogenetic changes during puberty, pregnancy, lactation, and regression. The recent identification of stem and progenitor populations in mouse and human mammary tissue has provided evidence that the mammary epithelium is organized in a hierarchical manner. Characterization of these normal epithelial subtypes is an important step toward understanding which cells are predisposed to oncogenesis. This review summarizes progress in the field toward defining constituent cells and key molecular regulators of the mammary epithelial hierarchy. Potential relationships between normal epithelial populations and breast tumor subtypes are discussed, with implications for understanding the cellular etiology underpinning breast tumor heterogeneity.

  20. Establishment of mammary gland model in vitro: culture and evaluation of a yak mammary epithelial cell line.

    PubMed

    Fu, Mei; Chen, Yabing; Xiong, Xianrong; Lan, Daoliang; Li, Jian

    2014-01-01

    This study aimed to establish yak mammary epithelial cells (YMECs) for an in vitro model of yak mammary gland biology. The primary culture of YMECs was obtained from mammary gland tissues of lactating yak and then characterized using immunocytochemistry, RT-PCR, and western blot analysis. Whether foreign genes could be transfected into the YMECs were examined by transfecting the EGFP gene into the cells. Finally, the effect of Staphylococcus aureus infection on YMECs was determined. The established YMECs retained the mammary epithelial cell characteristics. A spontaneously immortalized yak mammary epithelial cell line was established and could be continuously subcultured for more than 60 passages without senescence. The EGFP gene was successfully transferred into the YMECs, and the transfected cells could be maintained for a long duration in the culture by continuous subculturing. The cells expressed more antimicrobial peptides upon S.aureus invasion. Therefore, the established cell line could be considered a model system to understand yak mammary gland biology.

  1. Proteomic Analysis of Genistein Mammary Cancer

    DTIC Science & Technology

    2005-07-01

    American women. Even with improved technology for early detection and aggressive therapeutics, most often the disease is incurable once it is...the mammary glands of rats and we have been able to collect interstitial fluid. Task g) Now, we are investigating the use of chromatofocusing , 1-D gel...a chromatofocusing column from GE HealthCare (formally AmershamBioscience) and an automated gradient mixer and HPLC system (a BioRad "demo"). To date

  2. Mammary Cancer and Activation of Transposable Elements

    DTIC Science & Technology

    2015-03-01

    retrotransposon transcriptional activity, and retrotransposon-driven transcription of cellular genes in an engineered mouse model of mammary cancer. RNA-seq and...transcriptional activity, and retrotransposon-driven transcription of cellular genes . Retrotransposon promoters are well recognized to function as alternative...promoters for different cellular genes , generating chimeric transcripts that may or may not function in the same way as transcripts from the regular

  3. [Secret excretion from the mouse mammary gland].

    PubMed

    Tolkunov, Iu A; Balakina, G B; Markov, A G

    2000-02-01

    Histological studies revealed that the mammary gland nipple have smooth muscle fibres along the nipple channel. These fibres infiltrate the connective tissue parallel to the skin. The ring muscles are not obvious. Delays in the milk excretion in mice may be due to specifics of allocation and functioning of the nipple smooth muscles. To obtain milk, a mechanical action upon the nipple and a synchronised release of oxitocin into the blood are necessary.

  4. Leukocytes in Mammary Development and Cancer

    PubMed Central

    Coussens, Lisa M.; Pollard, Jeffrey W.

    2011-01-01

    Leukocytes, of both the innate and adaptive lineages, are normal cellular components of all tissues. These important cells not only are critical for regulating normal tissue homeostasis, but also are significant paracrine regulators of all physiologic and pathologic tissue repair processes. This article summarizes recent insights regarding the trophic roles of leukocytes at each stage of mammary gland development and during cancer development, with a focus on Murids and humans. PMID:21123394

  5. In-beam fission study for Heavy Element Synthesis

    NASA Astrophysics Data System (ADS)

    Nishio, Katsuhisa

    2013-12-01

    Fission fragment mass distributions were measured in heavy-ion induced fissions using 238U target nucleus. The measured mass distributions changed drastically with incident energy. The results are explained by a change of the ratio between fusion and qasifission with nuclear orientation. A calculation based on a fluctuation dissipation model reproduced the mass distributions and their incident energy dependence. Fusion probability was determined in the analysis. Evaporation residue cross sections were calculated with a statistical model in the reactions of 30Si + 238U and 34S + 238U using the obtained fusion probability in the entrance channel. The results agree with the measured cross sections for seaborgium and hassium isotopes.

  6. Oxytocin binding sites in bovine mammary tissue

    SciTech Connect

    Zhao, Xin.

    1989-01-01

    Oxytocin binding sites were identified and characterized in bovine mammary tissue. ({sup 3}H)-oxytocin binding reached equilibrium by 50 min at 20{degree}C and by 8 hr at 4{degree}C. The half-time of displacement at 20{degree}C was approximately 1 hr. Thyrotropin releasing hormone, adrenocorticotropin, angiotensin I, angiotensin II, pentagastrin, bradykinin, xenopsin and L-valyl-histidyl-L-leucyl-L-threonyl-L-prolyl-L-valyl-L-glutamyl-L-lysine were not competitive. In the presence of 10 nM LiCl, addition of oxytocin to dispersed bovine mammary cells, in which phosphatidylinositol was pre-labelled, caused a time and dose-dependent increase in radioactive inositiol monophosphate incorporation. The possibility that there are distinct vasopressin receptors in bovine mammary tissue was investigated. ({sup 3}H)-vasopressin binding reached equilibrium by 40 min at 20{degree}. The half-time of displacement at 20{degree}C was approximately 1 hr. The ability of the peptides to inhibit ({sup 3}H)-vasopressin binding was: (Thr{sup 4},Gly{sup 7})-oxytocin > Arg{sup 8}-vasopressin > (lys{sup 8})-vasopressin > (Deamino{sup 1},D-arg{sup 8})-vasopressin > oxytocin > d (CH{sub 2}){sub 5}Tyr(Me)AVP.

  7. Mammary ductoscopy: past, present, and future.

    PubMed

    Pereira, Bernadette; Mokbel, Kefah

    2005-04-01

    Mammary ductoscopy (MD) allows direct visual access to the mammary ducts, using fiberoptic microendoscopes inserted through the ductal opening onto the nipple surface. Therefore it has a potential role in the diagnosis and treatment of intraductal breast disease. This article describes the anatomy of the mammary ductal system, the early beginnings of MD, its ongoing evolution, and the need for further development for its future usage in increasing clinical indications. MD is a useful diagnostic adjunct in patients with pathological nipple discharge (PND) and can guide duct excision surgery. However, its potential use in the early detection of breast cancer, in guiding breast-conserving surgery (BCS) for cancer, and in the therapeutic ablation of intraductal disease, as well as in guiding risk-reducing strategies among high-risk women, requires further research and evaluation. The development of a biopsy kit that obtains adequate microbiopsy samples for histological diagnosis under direct visualization will enhance the use of this technique by breast surgeons and radiologists. Future developments also include combining MD with molecular diagnostic markers and optical biopsy systems for the diagnosis of premalignant and early malignant disease, and combining MD with radiofrequency for curative ablation of intraductal lesions.

  8. Mammary ductoscopy: current issues and perspectives.

    PubMed

    Uchida, Ken; Fukushima, Hisaki; Toriumi, Yasuo; Kawase, Kazumi; Tabei, Isao; Yamashita, Akinori; Nogi, Hiroko

    2009-01-01

    Until recently, the mammary duct had not been directly observed in vivo. Starting with the success of Teboul et al., studies of mammary ductoscopy (MD) for nipple discharge have been performed in Japan and other East Asian countries. Ductal lavage screening trials for breast cancer started in the 2000s. Concurrently, the number of English-language articles about MD increased. Sixty-nine English-language and 74 Japanese-language papers published in the last 19 years were reviewed. Important reports and studies were analyzed. MD has undergone significant technological development, and studies of MD have taken place in many countries. As a result, endoscopic images of the mammary duct have developed, and the endoscopic diagnosis for nipple discharge has become possible. MD-guided biopsy and surgery have been studied. Findings of MD are useful for diagnosing intraductal lesions with nipple discharge. As a result, MD has reduced the number and extent of microdochectomies. MD is also helpful in guiding breast-conserving surgery. Many pioneers have tried direct biopsy or interventions under MD, but further developments are necessary for its practical use.

  9. MATERNAL FLAXSEED DIET DURING PREGNANCY OR LACTATION INCREASES FEMALE RAT OFFSPRING’S SUSCEPTIBILITY TO CARCINOGEN-INDUCED MAMMARY TUMORIGENESIS

    PubMed Central

    Khan, Galam; Penttinen, Pauliina; Cabanes, Anna; Foxworth, Aaron; Chezek, Antonia; Masterpole, Kristen; Yu, Bin; Smeds, Annika; Halttunen, Teemu; Good, Carolyn; Mäkelä, Sari; Hilakivi-Clarke, Leena

    2013-01-01

    Flaxseed contains several dietary components that have been linked to low breast cancer risk; i.e., n-3 polyunsaturated fatty acids (PUFAs), lignans and fiber, but it also contains detectable levels of cadmium, a heavy metal that activates the estrogen receptor (ER). Since estrogenic exposures early in life modify susceptibility to develop breast cancer, we wondered whether maternal dietary intake of 5% or 10% flaxseed during pregnancy or lactation (between postpartum days 5 and 21) might affect 7,12-dimethylbenz[a]anthracene (DMBA) -induced mammary tumorigenesis in the rat offspring. Our data indicated that both in utero and postnatal 5% and 10% flaxseed exposures shortened mammary tumor latency, and 10% flaxseed exposure increased tumor multiplicity, compared to the controls. Further, when assessed in 8-week-old rats, in utero 10% flaxseed exposure increased lobular ER-α protein levels, and both in utero and postnatal flaxseed exposures dose-dependently reduced ER-β protein levels in the lobules and terminal end buds (TEBs). Exposures to flaxseed did not alter the number of TEBs or affect cell proliferation within the TEBs, lobules or ducts. In a separate group of immature rats that were fed 5% defatted flaxseed diet (flaxseed source different than in the diets fed to pregnant or lactating rats) for 7 days, cadmium exposure through the diet was 7-fold higher than allowed for humans by World Health Organization, and cadmium significantly accumulated in the liver and kidneys of the rats. It remains to be determined whether the increased mammary cancer in rats exposed to flaxseed through a maternal diet in utero or lactation was caused by cadmium present in flaxseed, and whether the reduced mammary ER-β content was causally linked to increased mammary cancer risk among the offspring. PMID:17398067

  10. Mammary extracellular matrix directs differentiation of testicular and embryonic stem cells to form functional mammary glands in vivo

    PubMed Central

    Bruno, Robert D.; Fleming, Jodie M.; George, Andrea L.; Boulanger, Corinne A.; Schedin, Pepper; Smith, Gilbert H.

    2017-01-01

    Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived cells to produce normal mammary epithelial trees within epithelial divested mouse mammary fat-pads. Conversely, ECMs isolated from omental fat and lung did not redirect testicular cells to a MEC fate, indicating the necessity of tissue specific components of the mECM. mECM preparations also completely inhibited teratoma formation from ESC inoculations. Further, a phenotypically normal ductal outgrowth resulted from a single inoculation of ESCs and mECM. To the best of our knowledge, this is the first demonstration of a tissue specific ECM driving differentiation of cells to form a functional tissue in vivo. PMID:28071703

  11. Technical note: Mammary gland ultrasonography to evaluate mammary parenchymal composition in prepubertal heifers.

    PubMed

    Albino, R L; Guimarães, S E F; Daniels, K M; Fontes, M M S; Machado, A F; Dos Santos, G B; Marcondes, M I

    2017-02-01

    Bovine mammary gland development studies are often terminal or involve invasive biopsy procedures. Therefore, noninvasive means of assessing mammary development should be considered as alternative methods in live animals. The objective was to test if mammary ultrasonography can be used as a noninvasive way to estimate mammary parenchyma (PAR) composition in prepubertal dairy heifers with different average daily body weight gains. In the 84 d preceding, the ultrasound exam heifers were maintained in 1 of 3 treatment groups. Individual heifers were fed a high gain (1 kg/d; n = 6), low gain (0.5 kg/d, n = 6), or maintenance (n = 6) treatment diet. To achieve desired body weight gains, heifers were fed differing amounts of the same silage-based diet. Mammary glands of 18 crossbred heifers Holstein:Gyr underwent a single mammary ultrasound exam immediately before heifer slaughter, which took place when heifers weighed 142.0 ± 8.0 kg and were 200 d old. The 4 mammary glands of each heifer were evaluated using a real-time B-mode ultrasound machine equipped with a 6.5-MHz micro-convex transducer. Digital images (8-bit) of glands were obtained and PAR was identified within gland. Average pixel values per unit of PAR area were determined for each gland and analyzed at the level of heifer. Pixel results were interpreted on the basis that lower average pixel values reflect PAR with relatively high amounts of protein as opposed to fat. To help validate that the pixel value within PAR is associated with composition of PAR, pixel findings were compared with histological [number of adipocytes in PAR (Nad) and epithelial area in PAR (Ep)] and biochemical [percent crude protein in PAR (%CP), percent ether extract in PAR (%EE), PAR weight (WPAR), and mammary fat pad weight (WFAT)] composition of PAR in these same heifers. Within PAR, %EE and WFAT were positively correlated with pixel values, whereas %CP, Ep, and Nad were negatively correlated. Parenchyma weight did not correlate

  12. In vivo MRI of early stage mammary cancers and the normal mouse mammary gland.

    PubMed

    Jansen, Sanaz A; Conzen, Suzanne D; Fan, Xiaobing; Markiewicz, Erica; Krausz, Thomas; Newstead, Gillian M; Karczmar, Gregory S

    2011-08-01

    Since the advent of screening mammography, approximately one-quarter of newly diagnosed breast cancers are at the earliest preinvasive stage of ductal carcinoma in situ (DCIS). Concomitant with this improvement in early detection has been a growing clinical concern that distinguishing aggressive from indolent DCIS is necessary to optimize patient management. Genetically engineered mouse models offer an appealing experimental framework in which to investigate factors that influence and predict progression of preinvasive neoplasias. Because of the small size of early stage carcinomas in mice, high-resolution imaging techniques are required to effectively observe longitudinal progression. The purpose of the present study was to evaluate the feasibility of MRI for assessment of in situ mammary neoplasias and early invasive mammary cancers that stochastically arise in mammary glands of C3(1) SV40 Tag transgenic mice. Additionally, images of normal mammary glands from wild-type FVB/N mice were acquired and compared with those from transgenic mice. Sixteen mice underwent MR examinations employing axial two-dimensional multi-slice gradient recalled echo scans (TR/TE =∼1000/5.5 ms) with fat suppression in a two-step process targeting both the upper and lower mammary glands. MRI successfully detected in situ and early invasive neoplasias in transgenic mice with high sensitivity and specificity. The average signal-to-noise ratio (SNR) of in situ lesions on fat-suppressed high-resolution T(1) -weighted images was 22.9, which was lower than that of invasive tumors, lymph nodes and muscle (average SNR of 29.5-34.9, p < 0.0001) but significantly higher than that of normal mammary tissue (average SNR = 5.5, p < 0.0001). Evaluation of wild-type mammary glands revealed no cancerous or benign lesions, and comparable image contrast characteristics (average SNR = 5.2) as compared with normal tissue areas of transgenic mice. This present study demonstrates that MRI is an excellent

  13. Cupric Ions Induce the Oxidation and Trigger the Aggregation of Human Superoxide Dismutase 1

    PubMed Central

    Li, Cheng; Xu, Wen-Chang; Xie, Zhen-Sheng; Pan, Kai; Hu, Jiao; Chen, Jie; Pang, Dai-Wen; Yang, Fu-Quan; Liang, Yi

    2013-01-01

    Background Amyotrophic lateral sclerosis (ALS), partly caused by the mutations and aggregation of human copper, zinc superoxide dismutase (SOD1), is a fatal degenerative disease of motor neurons. Because SOD1 is a major copper-binding protein present at relatively high concentration in motor neurons and copper can be a harmful pro-oxidant, we want to know whether aberrant copper biochemistry could underlie ALS pathogenesis. In this study, we have investigated and compared the effects of cupric ions on the aggregation of ALS-associated SOD1 mutant A4V and oxidized wild-type SOD1. Methodology/Principal Findings As revealed by 90° light scattering, dynamic light scattering, SDS-PAGE, and atomic force microscopy, free cupric ions in solution not only induce the oxidation of either apo A4V or Zn2-A4V and trigger the oligomerization and aggregation of oxidized A4V under copper-mediated oxidative conditions, but also trigger the aggregation of non-oxidized form of such a pathogenic mutant. As evidenced by mass spectrometry and SDS-PAGE, Cys-111 is a primary target for oxidative modification of pathological human SOD1 mutant A4V by either excess Cu2+ or hydrogen peroxide. The results from isothermal titration calorimetry show that A4V possesses two sets of independent binding sites for Cu2+: a moderate-affinity site (106 M-1) and a high-affinity site (108 M-1). Furthermore, Cu2+ binds to wild-type SOD1 oxidized by hydrogen peroxide in a way similar to A4V, triggering the aggregation of such an oxidized form. Conclusions/Significance We demonstrate that excess cupric ions induce the oxidation and trigger the aggregation of A4V SOD1, and suggest that Cu2+ plays a key role in the mechanism of aggregation of both A4V and oxidized wild-type SOD1. A plausible model for how pathological SOD1 mutants aggregate in ALS-affected motor neurons with the disruption of copper homeostasis has been provided. PMID:23755211

  14. Keratin 6 is not essential for mammary gland development

    PubMed Central

    Grimm, Sandra L; Bu, Wen; Longley, Mary Ann; Roop, Dennis R; Li, Yi; Rosen, Jeffrey M

    2006-01-01

    Introduction Keratin 6 (K6) has previously been identified as a marker of early mammary gland development and has also been proposed to be a marker of mammary gland progenitor cells. However, the function of K6 in the mammary gland was not known, so we examined the expression pattern of the protein during both embryonic and postnatal mammary development, as well as the mammary gland phenotype of mice that were null for both K6a and K6b isoforms. Method Immunostaining was performed to determine the expression pattern of K6a throughout mammary gland development, from the embryonic mammary bud to lactation. Double immunofluorescence was used to co-localize K6 with known markers of mammary gland development. Wild-type and K6ab-null mammary tissues were transplanted into the cleared fat pads of nude mice and the outgrowths were analyzed for morphology by whole-mount staining and for markers of mammary epithelium by immunostaining. Finally, progesterone receptor (PR) and bromodeoxyuridine co-localization was quantified by double immunofluorescence in wild-type and K6ab-null mammary outgrowths. Results Here we report that K6 is expressed earlier than described previously, by embryonic day 16.5. K6a is the predominant isoform expressed in the mammary gland, localized in the body cells and luminal epithelial cells but not in the cap cells or myoepithelial cells. Co-localization studies showed that most K6a-positive cells express steroid receptors but do not proliferate. When both the K6a and K6b genes are deleted, mammary gland development appears normal, with similar expression of most molecular markers examined in both the pubertal gland and the mature gland. Loss of K6a and K6b, however, leads to an increase in the number of steroid-receptor-positive cells, and increased co-localization of steroid receptor expression and proliferation was observed. Conclusion Although K6a was not essential for mammary gland development, loss of both K6a and K6b resulted in an increase in

  15. Effect of Thyroid Function on MNU-Induced Mammary Carcinogenesis.

    PubMed

    Vermey, Mackenzie L; Marks, Gregory T; Baldridge, Monika G

    2015-06-01

    Mammary cancer is a disease that affects many women. Extensive research has been conducted to elucidate which variables are involved in the development of this cancer. Studies have highlighted thyroid function as a modulator of tumor growth and development. Thyroxine and 3,3',5-triiodothyronine are responsible for regulating the development, differentiation, homeostasis, and metabolism of cells in the body including mammary tissue. Thyroid hormones also have estrogen-like effects on mammary cancer cell growth by regulating the estrogen receptor. The present study was designed to determine whether medically induced hyperthyroidism increases the multiplicity, prevalence, and mammary tumor burden in rats; and to elucidate whether surgically induced hypothyroidism conversely attenuates the rate of mammary cancer cell growth. Female Sprague-Dawley rats were randomly divided into three groups (euthyroid-control, hyperthyroid, and hypothyroid). Hyperthyroidism was induced via oral administration of levothyroxine; whereas, hypothyroidism was induced by thyroidectomy. Mammary carcinogenesis was induced with a single intraperitoneal injection of N-methyl-N-nitrosurea (MNU). Rats were sacrificed at 38 weeks, and the mammary tumors were excised, fixed for histology and analyzed. Analysis included evaluation of malignancy and immunohistochemistry for ER. MNU-induced mammary carcinogenesis among the groups resulted in a significant difference in tumor burden. The hyperthyroid group had a statistically higher tumor burden than did the euthyroid group, and the hypothyroid group had no tumors of mammary tissue origin at 38 weeks. All excised mammary tumors were ER alpha negative. These data support the hypothesis that thyroid function is one of potentially many factors that contribute to modulation of MNU-induced mammary tumor growth.

  16. Identification of rat mammary tumor-1 gene (RMT-1), which is highly expressed in rat mammary tumors.

    PubMed

    Chiou, S; Yoo, J; Loh, K C; Guzman, R C; Gopinath, G R; Rajkumar, L; Chou, Y C; Yang, J; Popescu, N C; Nandi, S

    2001-12-10

    Full-term pregnancy early in life results in a permanent reduction in lifetime breast cancer risk in women. Parous rats and mice are also refractory to chemical carcinogenesis. Therefore, investigation of the differences between mammary glands from virgin and parous rats would provide valuable information regarding the protective effects of early full-term pregnancy. In this report, we examined the gene expression patterns in mammary glands from virgin and parous Lewis rats. Using differential display technology, a novel 4.2 kb cDNA, designated rat mammary tumor-1 (RMT-1) was isolated. Northern blot analysis of RMT-1 showed that RMT-1 expression was higher in the pre-pubertal and pubertal stages during rat mammary gland development while it was down-regulated in mammary glands from mature virgin and parous rats. RMT-1 expression was highest in rat mammary cancers compared with either the mammary glands of virgin or parous rats. At the Northern blot sensitivity level, RMT-1 expression was found only in the mammary gland. Northern blot analysis also showed that the expression of this gene was found in 74% of N-methyl-nitrosourea (MNU)-induced mammary cancers while it was not found in MNU-induced cancers from other organs. The examination of the RMT-1 gene structure revealed that it consists of five exons spanning 5.9 kb. Using fluorescence in situ hybridization, the gene was localized on rat chromosome 1 band q 43-51. The present data show that there is a correlation between high RMT-1 expression and rat mammary carcinogenesis or decreased RMT-1 expression and parity associated refractoriness to chemically induced mammary carcinogenesis. However, whether or not RMT-1 gene has a functional role in these processes remains to be investigated.

  17. Mammary Development and Breast Cancer: A Wnt Perspective

    PubMed Central

    Yu, Qing Cissy; Verheyen, Esther M.; Zeng, Yi Arial

    2016-01-01

    The Wnt pathway has emerged as a key signaling cascade participating in mammary organogenesis and breast oncogenesis. In this review, we will summarize the current knowledge of how the pathway regulates stem cells and normal development of the mammary gland, and discuss how its various components contribute to breast carcinoma pathology. PMID:27420097

  18. Pim-1 kinase expression during murine mammary development

    SciTech Connect

    Gapter, Leslie A.; Magnuson, Nancy S.; Ng, Ka-yun; Hosick, Howard L. . E-mail: hosick@wsu.edu

    2006-07-07

    Pim-1 kinase phosphorylates substrates whose activities are linked to proliferation, survival, differentiation, and apoptosis. Although pim-1 is induced by hormones and cytokines, the hormonal control and contribution of Pim-1 to mammary gland development have not been evaluated. We examined Pim-1 expression in mammary cell lines, investigated whether Pim-1 levels could be altered in breast epithelia by mammogenic hormones, and evaluated Pim-1 expression during mammary development. We found that Pim-1 was elevated in most mammary carcinoma cell lines and progesterone increased Pim-1 protein to some extent in non-tumorigenic mammary epithelia. Pim-1 expression in situ was consistent with the documented profile of progesterone activity in mouse mammary glands. Pim-1 nuclear localization correlated with cytoplasmic distribution for its substrate, p21{sup CIP/Waf1}, and we found that Pim-1 and p21 associate in vitro. Our results suggest that Pim-1 expression may be regulated by progesterone during mammary development and Pim-1 associates with p21 in mammary epithelial cells.

  19. The Krakatau syndrome; a late complication of retroglandular mammary augmentation.

    PubMed

    Vuursteen, P J

    1992-01-01

    A late complication of retroglandular mammary augmentation is described, in which severe fibrous capsular contraction with calcification of the capsule causes pressure atrophy of the centre of the mammary gland and sometimes even atrophy of the underlying pectoralis major muscle. The complication was observed in six patients. Two representative cases are described and the treatment is discussed.

  20. Bovine mammary stem cells: Cell biology meets production agriculture

    USDA-ARS?s Scientific Manuscript database

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue ...

  1. Traumatic pseudoaneurysm of left internal mammary artery graft.

    PubMed

    Agathos, E A; Hussein, A; Trehan, H; Trenholme, S E; Floten, H S

    1993-10-01

    Traumatic pseudoaneurysm of the left internal mammary artery was recognized as a possible causal factor in the early recurrence of angina in a 51-year-old man. This patient underwent reoperation for revascularization with the left internal mammary artery graft in situ.

  2. P-Cadherin Expression in Feline Mammary Tissues

    PubMed Central

    Figueira, Ana Catarina; Teodósio, Ana Sofia; Carvalheira, Júlio; Lacerda, Manuela; de Matos, Augusto; Gärtner, Fátima

    2012-01-01

    The search for molecular markers in the feline mammary gland, namely, the adhesion molecules belonging to the cadherin family, is useful in the understanding of the development of mammary carcinomas in felines and humans. To study P-cadherin expression in the feline mammary gland, 61 samples of normal (n = 4), hyperplastic (n = 12), and neoplastic (n = 45) feline mammary tissues were examined. In both normal and hyperplastic mammary tissues as well as in benign tumours, P-cadherin immunolabelling was restricted to myoepithelial cells. In malignant tumours, however, there was an aberrant epithelial P-cadherin immunoexpression in 64.1% (n = 25) of cases, with a membranous and/or cytoplasmic pattern of distribution. A statistically significant relationship was seen between epithelial P-cadherin expression and malignant mammary lesions (P = 0.0001). In malignant mammary tumours, there was likewise a statistically significant relationship between aberrant P-cadherin immunoexpression and histological grade (P = 0.0132). Aberrant epithelial P-cadherin expression seems to be related to malignancy in the feline mammary gland. To confirm the results of this investigation, further studies with larger samples and follow-up studies are warranted. PMID:23091776

  3. Characterization of neutral TRH-like peptides in mammary gland, mammary tumors and milk.

    PubMed

    Ghilchik, M W; Tobaruela, M; del Rio-Garcia, J; Smyth, D G

    2000-06-01

    Three pyroglutamylpeptide amides, pGlu-Glu-Pro amide, pGlu-Phe-Pro amide and pGlu-Gln-Pro amide, with similar structures to thyrotropin-releasing hormone (TRH), have been identified previously in the male reproductive system. We report here that rat and human mammary gland contain neutral TRH-immunoreactive peptides which are not retained on cation or anion exchange chromatography and that similar peptides occur in the milk of rat, cow, ewe and sow. The TRH-like peptides in lyophilized milk from the cow were purified by gel exclusion chromatography, mini-column cation exchange chromatography and reversed phase high performance liquid chromatography (HPLC) and the chromatographed peptides were located by TRH radioimmunoassay (RIA). In each chromatographic system the major TRH-immunoreactive peptide from cow milk exhibited identical behavior to pGlu-Phe-Pro amide; in addition there were two minor TRH-immunoreactive components. The possible physiological role of the TRH-like peptides in the mammary gland is discussed. In a series of patients with breast carcinoma, mammary tumor tissue was shown to contain approximately four times more TRH-like peptide than normal mammary tissue from the same patient, raising the possibility that the TRH-like peptides may be implicated in tumor development.

  4. Mammary gland stem cells and their application in breast cancer.

    PubMed

    Yang, Xing; Wang, Hui; Jiao, Baowei

    2017-02-07

    The mammary gland is an organ comprising two primary lineages, specifically the inner luminal and the outer myoepithelial cell layers. Mammary gland stem cells (MaSCs) are highly dynamic and self-renewing, and can give rise to these mammary gland lineages. The lineages are responsible for gland generation during puberty as well as expansion during pregnancy. In recent years, researchers have focused on understanding how MaSCs are regulated during mammary gland development and transformation of breast cancer. Here, we summarize the identification of MaSCs, and how they are regulated by the signaling transduction pathways, mammary gland microenvironment, and non-coding RNAs (ncRNAs). Moreover, we debate the evidence for their serving as the origin of breast cancer, and discuss the therapeutic perspectives of targeting breast cancer stem cells (BCSCs). In conclusion, a better understanding of the key regulators of MaSCs is crucial for the clinical treatment of breast cancer.

  5. Stem cells in normal mammary gland and breast cancer.

    PubMed

    Luo, Jie; Yin, Xin; Ma, Tao; Lu, Jun

    2010-04-01

    The mammary gland is a structurally dynamic organ that undergoes dramatic alterations with age, menstrual cycle, and reproductive status. Mammary gland stem cells, the minor cell population within the mature organ, are thought to have multiple functions in regulating mammary gland development, tissue maintenance, major growth, and structural remodeling. In addition, accumulative evidence suggests that breast cancers are initiated and maintained by a subpopulation of tumor cells with stem cell features (called cancer stem cells). A variety of methods have been developed to identify and characterize mammary stem cells, and several signal transduction pathways have been identified to be essential for the self-renewal and differentiation of mammary gland stem cells. Understanding the origin of breast cancer stem cells, their relationship to breast cancer development, and the differences between normal and cancer stem cells may lead to novel approaches to breast cancer diagnosis, prevention, and treatment.

  6. Plk2 regulates mitotic spindle orientation and mammary gland development.

    PubMed

    Villegas, Elizabeth; Kabotyanski, Elena B; Shore, Amy N; Creighton, Chad J; Westbrook, Thomas F; Rosen, Jeffrey M

    2014-04-01

    Disruptions in polarity and mitotic spindle orientation contribute to the progression and evolution of tumorigenesis. However, little is known about the molecular mechanisms regulating these processes in vivo. Here, we demonstrate that Polo-like kinase 2 (Plk2) regulates mitotic spindle orientation in the mammary gland and that this might account for its suggested role as a tumor suppressor. Plk2 is highly expressed in the mammary gland and is required for proper mammary gland development. Loss of Plk2 leads to increased mammary epithelial cell proliferation and ductal hyperbranching. Additionally, a novel role for Plk2 in regulating the orientation of the mitotic spindle and maintaining proper cell polarity in the ductal epithelium was discovered. In support of a tumor suppressor function for Plk2, loss of Plk2 increased the formation of lesions in multiparous glands. Collectively, these results demonstrate a novel role for Plk2 in regulating mammary gland development.

  7. Proteomic analysis of microsomes from lactating bovine mammary gland.

    PubMed

    Peng, Lifeng; Rawson, Pisana; McLauchlan, Danyl; Lehnert, Klaus; Snell, Russell; Jordan, T William

    2008-04-01

    Mammary gland has multiple metabolic potential including for large-scale synthesis of milk proteins, carbohydrate, and lipids including nutrient triacylglycerols. We have carried out a proteomic analysis of mammary tissue to discover proteins that affect lipid metabolism. Unfractionated microsomes from lactating bovine mammary tissue were analyzed using one-dimensional SDS-PAGE with RPLC-ESI-MS/MS. This approach gave 703 proteins including 160 predicted transmembrane proteins. Proteins were classified according to their subcellular localizations and biological functions. Over 50 proteins were associated with cellular uptake, metabolism, and secretion of lipids, including some enzymes that have been previously associated with breast cancer and potential therapeutic targets. This database develops a proteomic view of the metabolic potential of mammary gland that can be expected to contribute to a greater understanding of gene expression and tissue remodeling associated with lactation, and to further dissection of normal and pathological processes in mammary tissue.

  8. Luminal progenitors restrict their lineage potential during mammary gland development.

    PubMed

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-02-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

  9. Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development

    PubMed Central

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-01-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes. PMID:25688859

  10. Mammary development and breast cancer: the role of stem cells.

    PubMed

    Ercan, C; van Diest, P J; Vooijs, M

    2011-06-01

    The mammary gland is a highly regenerative organ that can undergo multiple cycles of proliferation, lactation and involution, a process controlled by stem cells. The last decade much progress has been made in the identification of signaling pathways that function in these stem cells to control self-renewal, lineage commitment and epithelial differentiation in the normal mammary gland. The same signaling pathways that control physiological mammary development and homeostasis are also often found deregulated in breast cancer. Here we provide an overview on the functional and molecular identification of mammary stem cells in the context of both normal breast development and breast cancer. We discuss the contribution of some key signaling pathways with an emphasis on Notch receptor signaling, a cell fate determination pathway often deregulated in breast cancer. A further understanding of the biological roles of the Notch pathway in mammary stem cell behavior and carcinogenesis might be relevant for the development of future therapies.

  11. Mammary epithelial cells isolated from milk are a valuable, non-invasive source of mammary transcripts

    PubMed Central

    Boutinaud, Marion; Herve, Lucile; Lollivier, Vanessa

    2015-01-01

    Milk is produced in the udder by mammary epithelial cells (MEC). Milk contains MEC, which are gradually exfoliated from the epithelium during lactation. Isolation of MEC from milk using immunomagnetic separation may be a useful non-invasive method to investigate transcriptional regulations in ruminants’ udder. This review aims to describe the process of isolating MEC from milk, to provide an overview on the studies that use this method to analyze gene expression by qRT PCR and to evaluate the validity of this method by analyzing and comparing the results between studies. In several goat and cow studies, consistent reductions in alpha-lactalbumin mRNA levels during once-daily milking (ODM) and in SLC2A1 mRNA level during feed restriction are observed. The effect of ODM on alpha-lactalbumin mRNA level was similarly observed in milk isolated MEC and mammary biopsy. Moreover, we and others showed decreasing alpha-lactalbumin and increasing BAX mRNA levels with advanced stages of lactation in dairy cows and buffalo. The relevance of using the milk-isolated MEC method to analyze mammary gene expression is proven, as the transcript variations were also consistent with milk yield and composition variations under the effect of different factors such as prolactin inhibition or photoperiod. However, the RNA from milk-isolated MEC is particularly sensitive to degradation. This could explain the differences obtained between milk-isolated MEC and mammary biopsy in two studies where gene expression was compared using qRT-PCR or RNA Sequencing analyses. As a conclusion, when the RNA quality is conserved, MEC isolated from milk are a valuable, non-invasive source of mammary mRNA to study various factors that impact milk yield and composition (ODM, feeding level, endocrine status, photoperiod modulation, and stage of lactation). PMID:26579195

  12. Genetic Mechanisms in Apc-Mediated Mammary Tumorigenesis

    PubMed Central

    Kuraguchi, Mari; Ohene-Baah, Nana Yaw; Sonkin, Dmitriy; Bronson, Roderick Terry; Kucherlapati, Raju

    2009-01-01

    Many components of Wnt/β-catenin signaling pathway also play critical roles in mammary tumor development, yet the role of the tumor suppressor gene APC (adenomatous polyposis coli) in breast oncongenesis is unclear. To better understand the role of Apc in mammary tumorigenesis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-cre and WAP-cre transgenic mice that express Cre-recombinase in mammary progenitor cells and lactating luminal cells, respectively. Only the K14-cre–mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological heterogeneity, suggesting the multilineage progenitor cell origin of these tumors. These tumors harbored truncation mutation in a defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of β-catenin signaling. Activating mutations at codons 12 and 61 of either H-Ras or K-Ras were also found in a subset of these tumors. Expression profiles of acinar-type mammary tumors from K14-cre; ApcCKO/+ mice showed luminal epithelial gene expression pattern, and clustering analysis demonstrated more correlation to MMTV-neu model than to MMTV-Wnt1. In contrast, neither WAP-cre–induced Apc heterozygous nor homozygous mutations resulted in predisposition to mammary tumorigenesis, although WAP-cre–mediated Apc deficiency resulted in severe squamous metaplasia of mammary glands. Collectively, our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of β-catenin signaling optimal for mammary tumor development and explain partially the colon- but not mammary-specific tumor development in patients that carry germline mutations in APC. PMID:19197353

  13. Genistein-mediated inhibition of mammary stromal adipocyte differentiation limits expansion of mammary stem/progenitor cells by paracrine signaling

    USDA-ARS?s Scientific Manuscript database

    Mammary adiposity may contribute to breast cancer development and progression by releasing cytokines and other inflammatory mediators that promote mammary epithelial proliferation. We evaluated the effects of soy isoflavone genistein (GEN) on the adipogenic differentiation of a SV40-immortalized mou...

  14. Alcohol exposure in utero leads to enhanced prepubertal mammary development and alterations in mammary IGF and estradiol systems.

    PubMed

    Polanco, Tiffany A; Crismale-Gann, Catina; Cohick, Wendie S

    2011-08-01

    Exposure to alcohol during fetal development increases susceptibility to mammary cancer in adult rats. This study determined if early changes in mammary morphology and the insulin-like growth factor (IGF)/estradiol axis are involved in the mechanisms that underlie this increased susceptibility. Pregnant Sprague-Dawley rats were fed a liquid diet containing 6.7% ethanol (alcohol), an isocaloric liquid diet (pair-fed), or rat chow ad libitum from days 11 to 21 of gestation. At birth, female pups were cross-fostered to ad libitum-fed control dams. Offspring were euthanized at postnatal days (PND) 20, 40, or 80. Animals were injected with BrdU before euthanasia, then mammary glands, serum, and livers were collected. Mammary glands from animals exposed to alcohol in utero displayed increased epithelial cell proliferation and aromatase expression at PND 20 and 40. Mammary IGF-I mRNA was higher in alcohol-exposed animals relative to controls at PND 20, while mammary IGFBP-5 mRNA was lower in this group at PND 40. Hepatic IGF-I mRNA expression was increased at all time points in alcohol-exposed animals, however, circulating IGF-I levels were not altered. These data indicate that alcohol exposure in utero may advance mammary development via the IGF and estradiol systems, which could contribute to increased susceptibility to mammary cancer later in life.

  15. Characterization of Human Mammary Epithelial Stem Cells

    DTIC Science & Technology

    2008-10-01

    9 Appendix……………………………………………………………………………… 10 Eirew,P., Stingl,J., Raouf,A., Turashvili,G., Aparicio ,S., Emerman,J.T., and Eaves,C.J. A...Peter Eirew, John Stingl, Afshin Raouf, Gulisa Turashvili, Samuel Aparicio , Joanne Emerman and Connie Eaves. A method for quantifying normal human...Eirew, Afshin Raouf, John Stingl, Gulisa Turashvili, Allen Delaney, Joanne Emerman, Marco Marra and Samuel Aparicio . “Stem Cells in the Mammary Gland

  16. Mammary Cancer and Activation of Transposable Elements

    DTIC Science & Technology

    2013-09-01

    cytes and ADS-derived induced pluripotent stem cells (ADS-iPSCs) (19) and primary mouse ES cells to isolated sperm and oocytes (20). We selected an...051 59 5 92% H9-IMR90 5875 7 669 782 605 58 91% oocyte - ES cell (mouse) 4727 1 204 883 334 25 93% sperm - ES cell (mouse) 4580 4 364 748 1027 104 91...collaborator, Dr. Anne Peaston, developed a genetically engineered mouse model in which a specific mammary cell population is fluorescently marked upon

  17. Mammary fibroadenoma with pleomorphic stromal cells.

    PubMed

    Abid, Najla; Kallel, Rim; Ellouze, Sameh; Mellouli, Manel; Gouiaa, Naourez; Mnif, Héla; Boudawara, Tahia

    2015-01-01

    The presence of enlarged and pleomorphic nuclei is usually regarded as a feature of malignancy, but it may on occasion be seen in benign lesions such as mammary fibroadenomas. We present such a case of fibroadenoma occurring in a 37-year-old woman presenting with a self-palpable right breast mass. Histological examination of the tumor revealed the presence of multi and mononucleated giant cells with pleomorphic nuclei. The recognition of the benign nature of these cells is necessary for differential diagnosis from malignant lesions of the breast. fibroadenoma - pleomorphic stromal cells - atypia - breast.

  18. Bovine mammary gland X chromosome inactivation.

    PubMed

    Couldrey, C; Johnson, T; Lopdell, T; Zhang, I L; Littlejohn, M D; Keehan, M; Sherlock, R G; Tiplady, K; Scott, A; Davis, S R; Spelman, R J

    2017-07-01

    X chromosome inactivation (XCI) is a process by which 1 of the 2 copies of the X chromosomes present in female mammals is inactivated. The transcriptional silencing of one X chromosome achieves dosage compensation between XX females and XY males and ensures equal expression of X-linked genes in both sexes. Although all mammals use this form of dosage compensation, the complex mechanisms that regulate XCI vary between species, tissues, and development. These mechanisms include not only varying levels of inactivation, but also the nature of inactivation, which can range from being random in nature to driven by parent of origin. To date, no data describing XCI in calves or adult cattle have been reported and we are reliant on data from mice to infer potential mechanisms and timings for this process. In the context of dairy cattle breeding and genomic prediction, the implications of X chromosome inheritance and XCI in the mammary gland are particularly important where a relatively small number of bulls pass their single X chromosome on to all of their daughters. We describe here the use of RNA-seq, whole genome sequencing and Illumina BovineHD BeadChip (Illumina, San Diego, CA) genotypes to assess XCI in lactating mammary glands of dairy cattle. At a population level, maternally and paternally inherited copies of the X chromosome are expressed equally in the lactating mammary gland consistent with random inactivation of the X chromosome. However, average expression of the paternal chromosome ranged from 10 to 90% depending on the individual animal. These results suggest that either the mammary gland arises from 1 or 2 stem cells, or a nongenetic mechanism that skews XCI exists. Although a considerable amount of future work is required to fully understand XCI in cattle, the data reported here represent an initial step in ensuring that X chromosome variation is captured and used in an appropriate manner for future genomic selection. The Authors. Published by the

  19. Lgr6 labels a rare population of mammary gland progenitor cells that are able to originate luminal mammary tumours.

    PubMed

    Blaas, Leander; Pucci, Fabio; Messal, Hendrik A; Andersson, Agneta B; Josue Ruiz, E; Gerling, Marco; Douagi, Iyadh; Spencer-Dene, Bradley; Musch, Alexandra; Mitter, Richard; Bhaw, Leena; Stone, Richard; Bornhorst, Dorothee; Sesay, Abdul K; Jonkers, Jos; Stamp, Gordon; Malanchi, Ilaria; Toftgård, Rune; Behrens, Axel

    2016-12-01

    The mammary gland is composed of a complex cellular hierarchy with unusual postnatal plasticity. The identities of stem/progenitor cell populations, as well as tumour-initiating cells that give rise to breast cancer, are incompletely understood. Here we show that Lgr6 marks rare populations of cells in both basal and luminal mammary gland compartments in mice. Lineage tracing analysis showed that Lgr6(+) cells are unipotent progenitors, which expand clonally during puberty but diminish in adulthood. In pregnancy or following stimulation with ovarian hormones, adult Lgr6(+) cells regained proliferative potency and their progeny formed alveoli over repeated pregnancies. Oncogenic mutations in Lgr6(+) cells resulted in expansion of luminal cells, culminating in mammary gland tumours. Conversely, depletion of Lgr6(+) cells in the MMTV-PyMT model of mammary tumorigenesis significantly impaired tumour growth. Thus, Lgr6 marks mammary gland progenitor cells that can initiate tumours, and cells of luminal breast tumours required for efficient tumour maintenance.

  20. Immune cell location and function during post-natal mammary gland development.

    PubMed

    Reed, Johanna R; Schwertfeger, Kathryn L

    2010-09-01

    Post-natal mammary gland development requires complex interactions between the epithelial cells and various cell types within the stroma. Recent studies have illustrated the importance of immune cells and their mediators during the various stages of mammary gland development. However, the mechanisms by which these immune cells functionally contribute to mammary gland development are only beginning to be understood. This review provides an overview of the localization of immune cells within the mammary gland during the various stages of post-natal mammary gland development. Furthermore, recent studies are summarized that illustrate the mechanisms by which these cells are recruited to the mammary gland and their functional roles in mammary gland development.

  1. Measurement of The Ion-induced Electron Yields From Thin Carbon Foils For Low-energy Ions

    NASA Astrophysics Data System (ADS)

    Allegrini, F.; Wimmer-Schweingruber, R. F.; Wurz, P.; Hohl, M.; Wieser, M.; Luethi, B.; Bochsler, P.

    Energetic ions passing thin carbon foils cause electron emission from the entrance and exit surface. Carbon foils are used in many Time-Of-Flight (TOF) solar wind mass spectrometers to produce the start pulse for TOF measurements. The number of emitted electrons depends on the energy of the incoming ion, its mass, and other parameters, and is known for only a few elements in the solar wind energy range. This number is of great importance in determining abundance ratios of different ele- ments using measurements of TOF mass spectrometers based on the carbon-foil tech- nique (such as the Ulysses/- and ACE/SWICS instruments, or SOHO/CELIAS/MTOF, -/CTOF, -/STOF, or WIND/MASS, or ACE/SWIMS). We have developed an appara- tus for measuring the ion-induced electron yields. We report measurements of the ion induced electron yields of H, O, N, Ne, Na, Ca, Ar, and Fe in the energy range from 0.15 to 60 keV/u for various foil thicknesses and initial charge states, and compare our results with the literature.

  2. 60 keV Ar⁺-ion induced modification of microstructural, compositional, and vibrational properties of InSb

    SciTech Connect

    Datta, D. P.; Garg, S. K.; Som, T.; Satpati, B.; Kanjilal, A.; Dhara, S.; Kanjilal, D.

    2014-10-14

    Room temperature irradiation of InSb(111) by 60 keV Ar⁺-ions at normal (0°) and oblique (60°) angles of incidence led to the formation of nanoporous structure in the high fluence regime of 1×10¹⁷ to 3×10¹⁸ ions cm⁻². While a porous layer comprising of a network of interconnected nanofibers was generated by normal ion incidence, evolution of plate-like structures was observed for obliquely incident ions. Systematic studies of composition and structure using energy dispersive x-ray spectroscopy, Raman spectroscopy, x-ray photoelectron spectroscopy, Raman mapping, grazing incidence x-ray diffraction, and cross-sectional transmission electron microscopy revealed a high degree of oxidation of the ion-induced microstructures with the presence of In₂O₃ and Sb₂O₃ phases and presence of nanocrystallites within the nanoporous structures. The observed structural evolution was understood in terms of processes driven by ion-induced defect accumulation within InSb.

  3. An ultra-compact setup for measuring ion-induced electron emission statistics

    NASA Astrophysics Data System (ADS)

    Schrempf, D.; Meissl, W.; Aumayr, F.

    2013-12-01

    Important studies on electron emission phenomena during energetic projectile impact (ions, atoms, electrons) on surfaces are based on the so-called electron emission statistics (EES) technique. In this contribution a novel and very compact version of such an EES detection scheme is presented which no longer requires a heavy NIM-crate with power supply to be operated at high voltage potential. These parts are replaced by small and low cost electronic components, which can be operated using a battery pack only. Even the pulse height analysis is now performed at high voltage and just the resulting pulse height spectrum is communicated by optical fibers to the measurement PC at ground potential. EES-spectra for Ar9+ ion impact on Au are presented to demonstrate the performance of this new EES measurement setup.

  4. Prognosis of mammary carcinoma in young women.

    PubMed

    Gogas, J; Skalkeas, G

    1975-09-01

    One hundred and sixty-two women with carcinoma of the breast, age 40 years or younger, were treated from 1950 to 1969. Mammary cancer is not uncommon in this age group. The 5 year survival rate among our operable patients was about 50 percent. The 5 year survival rate among patients 20 to 35 years of age was slightly higher than that in patients 36 to 40 years old. In stage B and more advanced breast cancer in young women, the outlook was poorer than in women 41 years and older. When axillary involvement is present during gestation or in the immediate postpartum period, the prognosis is especially poor. Young women have an unusually high proportion (35 percent) of low-grade, infrequently metastasizing tumors, such as medullary, intraductal, papillary, and lobular carcinomas. The presence of cancer in the axillary nodes at operation is the most important factor affecting prognosis in mammary cancer. From this study we can see no reason to consider carcinoma of the breast in young women a more lethal disease than that seen in their older counterparts.

  5. Periareolar techniques for mammary reduction and elevation.

    PubMed

    de Benito, J; Sanza, I F

    1993-01-01

    Between June 1990 and June 1992 we carried out 56 breast operations: 18 reductions, 32 mastopexies, and 6 implant changes. The surgical techniques used in all cases basically consisted of three phases: the periareolar incision, the creation of the superior pedicle with two medial and lateral flaps, and the "anchoring," crossed by both flaps in order to hold up the mammary gland. The diameter of the "doughnut" of skin that we had to deepidermize varied between 5 and 15 cm, thus raising the nipple-areola complex by as much as 10 cm. The volume of tissue removed from the hypertrophic breast ranged from 70 to 520 g. In 24 of the 32 mastopexies, the use of a silicone implant was necessary in order to provide greater volume, texture, and better mammary contour. In these cases the size of the prostheses varied between 120 and 300 cc. All patients completed the postop followup in the normal way. Only three patients suffered a slight dehiscence of the periareolar suture, which was solved within a few days of the operation by means of a Friedreich. The periareolar cutaneous pleats and the hardness of the breast gradually disappeared, as predicted, within a period of 3-4 months; afterward the breast looked perfectly natural.

  6. Surface scanning: an application to mammary surgery

    NASA Astrophysics Data System (ADS)

    Rigotti, Camilla; Ferrigno, Giancarlo; Aliverti, Andrea; Pedotti, Antonio

    1998-04-01

    The possibility of mathematically describing the body surface represents a useful tool for several medical sectors, such as prosthetics or plastic surgery, and could improve diagnosis and objective evaluation of deformities and the follow-up of progressive diseases. The approach presented is based on the acquisition of a surface scanned by a laser beam. The 3D coordinates of the spot generated on the surface by the laser beam are computed by an automatic image analyzer. Using at least two different views of the subject, the 3D coordinates are obtained by stereophotogrammetry. A software package for graphic representation and extraction of linear superficial and volumetric features from the acquired surface has been developed and some preliminary results with mammary reconstruction are presented. A good mammary reconstruction after mastectomy must achieve two results. First, the reconstruction should follow the patients' wishes and second, the reconstructed breast should be as similar as possible to the contralateral one. To achieve these goals, a knowledge of breast volume, area, and shape features are essential for the surgeon. In such a context, this system could be a valuable tool in improving breast reconstructive surgery.

  7. CELL CONTACTS IN THE MOUSE MAMMARY GLAND

    PubMed Central

    Pitelka, Dorothy R.; Hamamoto, Susan T.; Duafala, Joan G.; Nemanic, Michael K.

    1973-01-01

    The nature and distribution of cell contacts have been examined in thin sections and freeze-fracture replicas of mammary gland samples from female C3H/Crgl mice at stages from birth through pregnancy, lactation, and postweaning involution. Epithelial cells of major mammary ducts at all stages examined are linked at their luminal borders by junctional complexes consisting of tight junctions, variable intermediate junctions, occasional small gap junctions, and one or more series of desmosomes. Scattered desmosomes and gap junctions link ductal epithelial and myoepithelial cells in all combinations; hemidesmosomes attach myoepithelial cells to the basal lamina. Freeze-fracture replicas confirm the erratic distribution of gap junctions and reveal a loose, irregular network of ridges comprising the continuous tight-junctional belts. Alveoli develop early in gestation and initially resemble ducts. Later, as alveoli and small ducts become actively secretory, they lose all desmosomes and most intermediate junctions, whereas tight and gap junctions persist, The tight-junctional network becomes compact and orderly, its undulating ridges oriented predominantly parallel to the luminal surface. It is suggested that these changes in junctional morphology, occurring in secretory cells around parturition, may be related to the greatly enhanced rate of movement of milk precursors and products through the lactating epithelium, or to the profound and recurrent changes in shape of secretory cells that occur in relation to myoepithelial cell contraction, or to both. PMID:4569313

  8. Heavy ion microscopy of single event upsets in CMOS SRAMs

    SciTech Connect

    Metzger, S.; Dreute, J.; Heinrich, W.; Roecher, H. ); Fischer, B.E. ); Harboe-Soerensen, R.; Adams, L. )

    1994-06-01

    The single event upset (SEU) imaging has been applied at the GSI heavy ion microprobe to determine the sensitivity of integrated circuits (IC) to heavy ion irradiation. This method offers the possibility to directly image those parts of an IC which are sensitive to ion-induced malfunctions. By a 3-dimensional simulation of charge collection across p-n-micro-junctions the authors can predict SEU cross-sections. For a MHS65162 2k [times] 8bit CMOS SRAM they found two regions per bit with different sensitivity and measured a total cross-section of (71[+-]18)[mu]m[sup 2] for a bitflip per cell and simulated 60[mu]m[sup 2] with an argon beam of 1.4 MeV/nucl. (LET of 19.7 MeV/mg/cm[sup 2]).

  9. Disruption of reelin signaling alters mammary gland morphogenesis

    PubMed Central

    Khialeeva, Elvira; Lane, Timothy F.; Carpenter, Ellen M.

    2011-01-01

    Reelin signaling is required for appropriate cell migration and ductal patterning during mammary gland morphogenesis. Dab1, an intracellular adaptor protein activated in response to reelin signaling, is expressed in the developing mammary bud and in luminal epithelial cells in the adult gland. Reelin protein is expressed in a complementary pattern, first in the epithelium overlying the mammary bud during embryogenesis and then in the myoepithelium and periductal stroma in the adult. Deletion in mouse of either reelin or Dab1 induced alterations in the development of the ductal network, including significant retardation in ductal elongation, decreased terminal branching, and thickening and disorganization of the luminal wall. At later stages, some mutant glands overcame these early delays, but went on to exhibit enlarged and chaotic ductal morphologies and decreased terminal branching: these phenotypes are suggestive of a role for reelin in spatial patterning or structural organization of the mammary epithelium. Isolated mammary epithelial cells exhibited decreased migration in response to exogenous reelin in vitro, a response that required Dab1. These observations highlight a role for reelin signaling in the directed migration of mammary epithelial cells driving ductal elongation into the mammary fat pad and provide the first evidence that reelin signaling may be crucial for regulating the migration and organization of non-neural tissues. PMID:21266412

  10. STAT signaling in mammary gland differentiation, cell survival and tumorigenesis.

    PubMed

    Haricharan, S; Li, Y

    2014-01-25

    The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programmed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer.

  11. STAT signaling in mammary gland differentiation, cell survival and tumorigenesis

    PubMed Central

    Haricharan, S; Li, Y

    2013-01-01

    The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer. PMID:23541951

  12. Alpha basic crystallin expression in canine mammary tumors.

    PubMed

    Guvenc, Tolga; Gulbahar, Mustafa Yavuz; Yarim, Murat; Kabak, Yonca Betil; Karayigit, Onder; Sozmen, Mahmut

    2012-03-01

    The aim of this study was to evaluate prognostic and/or diagnostic factors of canine mammary tumors by immunohistochemically analyzing the expression of alpha basic crystallin (αB-c). For this, formalin-fixed, paraffin-embedded blocks of 51 naturally-occurring canine mammary tumors (11 benign and 40 malignant) were used. Tissue from eight normal canine mammary glands were served as a control. Immunohistochemically, in the control mammary tissues, a few luminal epithelial cells were αB-c positive but myoepithelial cells were negative. In benign or simple type malignant tumors, αB-c expression was observed in luminal epithelial cells while the myoepithelial basal cells were negative. In benign or complex type malign tumors, positive staining was predominantly found in the cytoplasm of epithelial cells. Immunoreactivity of αB-c was also observed in neoplastic myoepithelial cells. Statistically, the number of cells immunolabeled with αB-c was found to be significantly different among tissues from normal canine mammary glands, benign lesions, and malignant tumors (p < 0.05). αB-c immunoreactivity was higher in malignant tumors than the control mammary tissues (p < 0.001). Data obtained in the current study revealed a strong association between high expression levels of αB-c and primary mammary gland tumors in canines.

  13. The spectrum of STAT functions in mammary gland development

    PubMed Central

    Hughes, Katherine; Watson, Christine J.

    2012-01-01

    The signal transducer and activator of transcription (STAT) family of transcription factors have a spectrum of functions in mammary gland development. In some cases these roles parallel those of STATs in other organ systems, while in other instances the function of individual STATs in the mammary gland is specific to this tissue. In the immune system, STAT6 is associated with differentiation of T helper cells, while in the mammary gland, it has a fundamental role in the commitment of luminal epithelial cells to the alveolar lineage. STAT5A is required for the production of luminal progenitor cells from mammary stem cells and is essential for the differentiation of milk producing alveolar cells during pregnancy. By contrast, the initiation of regression following weaning heralds a dramatic and specific activation of STAT3, reflecting its pivotal role in the regulation of cell death and tissue remodeling during mammary involution. Although it has been demonstrated that STAT1 is regulated during a mammary developmental cycle, it is not yet determined whether it has a specific, non-redundant function. Thus, the mammary gland constitutes an unusual example of an adult organ in which different STATs are sequentially activated to orchestrate the processes of functional differentiation, cell death and tissue remodeling. PMID:24058764

  14. A review of mammary ductoscopy in breast cancer.

    PubMed

    Yamamoto, Daigo; Tanaka, Kanji

    2004-01-01

    Breast carcinoma and hyperplasia are thought to start in the lining of the breast duct. Mammary ductoscopy is an emerging technique allowing direct visual access of the ductal system of the breast through the nipple. This article reviews and discusses the utility of mammary ductoscopy. Abnormalities can be identified successfully by mammary ductoscopy, and intraductal biopsy can be used when the tumor is a polypoid type. Ductal lavage using microcatheters is effective in identifying malignant cells in high-risk women and this has stimulated interest in exploring the role of mammary ductoscopy in breast cancer screening. Mammary ductoscopy combined with ductal lavage may have a role in the management of patients with nipple discharge, the guiding of breast-conserving surgery for cancer, and in screening for high-risk women. The addition of molecular and genetic analysis of cells obtained by mammary ductoscopy are likely to enhance the use of this technique. Mammary ductoscopy techniques are safe and appear useful for detecting abnormalities in the breast. The additional molecular biologic study or ductal lavage may enhance the ability to direct and limit subsequent surgery when removing the offending lesions.

  15. Mammary gland-specific ablation of focal adhesion kinase reduces the incidence of p53-mediated mammary tumour formation

    PubMed Central

    van Miltenburg, M H A M; van Nimwegen, M J; Tijdens, I; Lalai, R; Kuiper, R; Klarenbeek, S; Schouten, P C; de Vries, A; Jonkers, J; van de Water, B

    2014-01-01

    Background: Elevated expression of focal adhesion kinase (FAK) occurs in numerous human cancers including colon-, cervix- and breast cancer. Although several studies have implicated FAK in mammary tumour formation induced by ectopic oncogene expression, evidence supporting a role for FAK in spontaneous mammary tumour development caused by loss of tumour suppressor genes such as p53 is lacking. Alterations in the tumour suppressor gene p53 have been implicated in over 50% of human breast cancers. Given that elevated FAK expression highly correlates with p53 mutation status in human breast cancer, we set out to investigate the importance of FAK in p53-mediated spontaneous mammary tumour development. Methods: To directly assess the role of FAK, we generated mice with conditional inactivation of FAK and p53. We generated female p53lox/lox/FAK+/+/WapCre, p53lox/lox/FAKflox/+/WapCre and p53lox/lox/FAKflox/−/WapCre mice, and mice with WapCre-mediated conditional expression of p53R270H, the mouse equivalent of human p53R273H hot spot mutation, together with conditional deletion of FAK, P53R270H/+/FAKlox/+/WapCre and p53R270H/+/FAKflox/−/WapCre mice. All mice were subjected to one pregnancy to induce WapCre-mediated deletion of p53 or expression of p53 R270H, and Fak genes flanked by two loxP sites, and subsequently followed the development of mammary tumours. Results: Using this approach, we show that FAK is important for p53-induced mammary tumour development. In addition, mice with the mammary gland-specific conditional expression of p53 point mutation R270H, the mouse equivalent to human R273H, in combination with conditional deletion of Fak showed reduced incidence of p53R270H-induced mammary tumours. In both models these effects of FAK were related to reduced proliferation in preneoplastic lesions in the mammary gland ductal structures. Conclusions: Mammary gland-specific ablation of FAK hampers p53-regulated spontaneous mammary tumour formation. Focal adhesion

  16. Sequencing the transcriptome of milk production: milk trumps mammary tissue

    PubMed Central

    2013-01-01

    Background Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. Results We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. Conclusions RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation. PMID:24330573

  17. Tissue-specific ceruloplasmin gene expression in the mammary gland.

    PubMed Central

    Jaeger, J L; Shimizu, N; Gitlin, J D

    1991-01-01

    Using a ceruloplasmin cDNA clone in RNA blot analysis, a single 3.7 kb ceruloplasmin-specific transcript was detected in rat mammary gland tissue from pregnant and lactating animals. Ceruloplasmin gene expression in the mammary gland was tissue-specific, with no evidence of expression in brain, heart or other extrahepatic tissues. Ceruloplasmin mRNA was also detected in mammary gland tissue from male, virgin female and non-pregnant/multiparous animals, and the abundance of ceruloplasmin-specific transcripts in virgin female rats was independent of their stage of oestrus. In virgin female mammary gland the content of ceruloplasmin mRNA was 20% of that in hepatic tissue from these animals and approx. 2-3-fold greater than that found in mammary gland tissue of pregnant or lactating animals. Development studies revealed ceruloplasmin gene expression in male and female mammary gland by only 2 weeks of age, prior to the onset of puberty. Biosynthetic studies indicated that the ceruloplasmin mRNA in mammary gland tissue was translated into a 132 kDa protein qualitatively similar to that synthesized in liver. By in situ hybridization, ceruloplasmin gene expression was localized to the epithelium lining the mammary gland alveolar ducts, without evidence of expression in the surrounding mesenchyme. Ceruloplasmin gene expression was also detected in a human breast adenocarcinoma cell line and in biopsy tissue from women with invasive ductal carcinoma. Taken together, these data indicate that the mammary gland is a prominent site of extrahepatic ceruloplasmin gene expression and add to the evidence that ceruloplasmin biosynthesis is associated with growth and differentiation in non-hepatic tissues. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:1764031

  18. Proteolytic maturation of protein C upon engineering the mouse mammary gland to express furin.

    PubMed Central

    Drews, R; Paleyanda, R K; Lee, T K; Chang, R R; Rehemtulla, A; Kaufman, R J; Drohan, W N; Luboń, H

    1995-01-01

    Endoproteolytic processing of the human protein C (HPC) precursor to its mature form involves cleavage of the propeptide after amino acids Lys-2-Arg-1 and removal of a Lys156-Arg157 dipeptide connecting the light and heavy chains. This processing was inefficient in the mammary gland of transgenic mice and pigs. We hypothesized that the protein processing capacity of specific animal organs may be improved by the coexpression of selected processing enzymes. We tested this by targeting expression of the human proprotein processing enzyme, named paired basic amino acid cleaving enzyme (PACE)/furin, or an enzymatically inactive mutant, PACEM, to the mouse mammary gland. In contrast to mice expressing HPC alone, or to HPC/PACEM bigenic mice, coexpression of PACE with HPC resulted in efficient conversion of the precursor to mature protein, with cleavage at the appropriate sites. These results suggest the involvement of PACE in the processing of HPC in vivo and represent an example of the engineering of animal organs into bioreactors with enhanced protein processing capacity. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7479820

  19. Bilateral internal mammary arteries: evidence and technical considerations

    PubMed Central

    Edelman, J. James B.; Wilson, Michael K.

    2013-01-01

    Bilateral internal mammary artery (BIMA) grafts are used for coronary revascularisation by only a minority of surgeons, despite a growing body of evidence suggesting improved survival when compared to use of only one internal mammary artery with additional saphenous vein grafts. Herein we review the evidence supporting revascularisation with BIMA and suggest reasons why the majority of surgeons use only one internal mammary artery. We discuss technical considerations, various graft combinations and the use of BIMA to facilitate anaortic off-pump coronary artery bypass (OPCAB). PMID:23977638

  20. Angiotensin converting enzyme from sheep mammary, lingual and other tissues.

    PubMed

    Rao, N Mallikarjuna; Udupa, E G Padmanabha

    2007-11-01

    Occurrence of angiotensin converting enzyme (ACE) in mammary gland and tongue taste epithelium was demonstrated for the first time. Six times higher ACE activity in lactating mammary gland, than non-lactating mammary gland, suggested pregnancy and lactation hormonal dependent expression of ACE in female mammals. ACE activity was highest in choroid plexus, less in spinal cord and moderate in cerebrum, medulla, cerebellum and pons. Distribution of ACE in different regions of skin, kidney and among other tissues was different. Presence of ACE in adrenal glands, pancreas, bone marrow and thyroid gland indicated functions other than blood pressure homeostasis for this enzyme.

  1. Mammary artery harvesting using the Da Vinci Si robotic system

    PubMed Central

    Canale, Leonardo Secchin; Bonatti, Johannes

    2014-01-01

    Internal mammary artery harvesting is an essential part of any coronary artery bypass operation. Totally endoscopic coronary artery bypass graft surgery has become reality in many centers as a safe and effective alternative to conventional surgery in selected patients. Internal mammary artery harvesting is the initial part of the procedure and should be performed equally safely if one wants to achieve excellence in patency rates for the bypass. We here describe the technique for mammary harvesting with the Da Vinci Si robotic system. PMID:24896171

  2. Application of ion-induced nucleation mass spectrometry in the analysis of trace gases evolved from a polyimide film during the thermal curing stages

    NASA Technical Reports Server (NTRS)

    Smith, A. C.

    1982-01-01

    Trace gases evolved from a polyimide film during its thermal curing stages have been studied using ion-induced nucleation mass spectrometry. The technique involved exposing the test gas sample to a low energy beta source and recording the masses of the ion-induced molecular clusters formed in the reaction chamber. On the basis of the experimentally observed molecular cluster spectra, it has been concluded that the dominant trace component had a molecular weight of 87 atomic mass units. This component has been identified as a molecule of dimethylacetamide (DMAC) which had been used as a solvent in the preparation of the test polyimide specimen. This identification has been further confirmed by comparing the spectra of the test gas sample and the DMAC calibration sample obtained with a conventional mass spectrometer. The advantages of the ion-induced nucleation mass spectrometer versus the conventional mass spectrometer are discussed.

  3. Reorientation of the crystalline planes in confined single crystal nickel nanorods induced by heavy ion irradiation

    NASA Astrophysics Data System (ADS)

    Misra, Abha; Tyagi, Pawan K.; Rai, Padmnabh; Misra, D. S.; Ghatak, Jay; Satyam, P. V.; Avasthi, D. K.

    2006-08-01

    In a recent letter Tyagi et al. [Appl. Phys. Lett. 86, 253110 (2005)] have reported the special orientation of nickel planes inside multiwalled carbon nanotubes (MWCNTs) with respect to the tube axis. Heavy ion irradiation has been performed with 1.5MeV Au2+ and 100MeV Au7+ ions on these nickel filled MWCNTs at fluences ranging from 1012to1015ions/cm2 at room temperature. Ion-induced modifications have been studied using high-resolution transmission electron microscopy. The diffraction pattern and the lattice imaging showed the presence of ion-induced planar defects on the tube walls and completely amorphized encapsulated nickel nanorods. The results are discussed in terms of thermal spike model.

  4. Ab initio treatment of ion-induced charge transfer dynamics of isolated 2-deoxy-D-ribose.

    PubMed

    Bacchus-Montabonel, Marie-Christine

    2014-08-21

    Modeling-induced radiation damage in biological systems, in particular, in DNA building blocks, is of major concern in cancer therapy studies. Ion-induced charge-transfer dynamics may indeed be involved in proton and hadrontherapy treatments. We have thus performed a theoretical approach of the charge-transfer dynamics in collision of C(4+) ions and protons with isolated 2-deoxy-D-ribose in a wide collision energy range by means of ab initio quantum chemistry molecular methods. The comparison of both projectile ions has been performed with regard to previous theoretical and experimental results. The charge transfer appears markedly less efficient with the 2-deoxy-D-ribose target than that with pyrimidine nucleobases, which would induce an enhancement of the fragmentation process in agreement with experimental measurements. The mechanism has been analyzed with regard to inner orbital excitations, and qualitative tendencies have been pointed out for studies on DNA buiding block damage.

  5. Photoluminescent Au-Ge composite nanodots formation on SiO2 surface by ion induced dewetting

    NASA Astrophysics Data System (ADS)

    Datta, D. P.; Siva, V.; Singh, A.; Kanjilal, D.; Sahoo, P. K.

    2017-09-01

    Medium energy ion irradiation on a bilayer of Au and Ge on SiO2 is observed to result in gradual morphological evolution from an interconnected network to a nanodot array on the insulator surface. Structural and compositional analyses reveal composite nature of the nanodots, comprising of both Au and Ge. The growing nanostructures are found to be photoluminescent at room temperature where the emission intensity and wavelengths vary with morphology. The growth of such nanostructures can be understood in terms of dewetting of the metal layer under ion irradiation due to ion-induced melting along the ion tracks. The visible PL emission is found to be related with evolution of the Au-Ge nanodots. The study indicates a route towards single step synthesis of metal-semiconductor nanodots on insulator surface.

  6. Selective ion-induced intermixing and damage in low-dimensional GaN/AlN quantum structures.

    PubMed

    Redondo-Cubero, A; Lorenz, K; Wendler, E; Carvalho, D; Ben, T; Morales, F M; García, R; Fellmann, V; Daudin, B

    2013-12-20

    Ion-induced intermixing and damage is evaluated in GaN/AlN superlattices of quantum dots (QDs) and quantum wells (QWs) using 100 keV Ar(+) implantation at low temperature (15 K). Despite the similar damage build up at low fluences, a significant increase of the damage accumulation takes place for QDs at high fluences. Elemental depth profiles were fitted with a diffusion model, revealing the higher intermixing efficiency in QD superlattices, significantly higher than for QWs. The scaling of diffusion length with the local fluence and defect concentration is understood on the basis of cascade mixing and migration of defects in the cation sublattice. The selective intermixing/damage of QDs is explained by the promotion of lateral diffusion mechanisms that result in smooth interfaces, as well as by an enhanced diffusivity due to the characteristic strain distribution in QD superlattices.

  7. The effects of the Fermi level on ion induced electron emission from chemically and sputter cleaned semiconductors

    NASA Astrophysics Data System (ADS)

    Urrabazo, David; Overzet, Lawrence J.

    2015-09-01

    Plasma interactions with semiconductors comprise a variety of interesting phenomena in addition to etching and deposition. One such phenomenon is the process of low energy ion induced electron emission (IIEE). IIEE has historically been viewed as extremely surface sensitive; but recent measurements have suggested that the IIEE yield from semiconductors, unlike metals, may in fact depend on the sub-surface properties as well. We investigated the effects of the surface and sub-surface properties (doping type, Fermi level, cleanliness level) on the relative IIEE yields from Si and Ge. Our measurements found that the relative IIEE yields did not depend on the doping type to a significant degree independent of the level of cleanliness.

  8. Mammary stem cell research in veterinary science: an update.

    PubMed

    Borena, Bizunesh M; Bussche, Leen; Burvenich, Christian; Duchateau, Luc; Van de Walle, Gerlinde R

    2013-06-15

    The mammary gland is an organ with a remarkable regenerative capacity that can undergo multiple cycles of proliferation, lactation, and involution. Growing evidence suggests that these changes are driven by the coordinated division and differentiation of mammary stem cell populations (MaSC). Whereas information regarding MaSC and their role in comparative mammary gland physiology is readily available in human and mice, such information remains scarce in most veterinary mammal species such as cows, horses, sheep, goats, pigs, and dogs. We believe that a better knowledge on the MaSC in these species will not only help to gain more insights into mammary gland (patho) physiology in veterinary medicine, but will also be of value for human medicine. Therefore, this review summarizes the current knowledge on stem cell isolation and characterization in different mammals of veterinary importance.

  9. Mammary Stem Cell Research in Veterinary Science: An Update

    PubMed Central

    Borena, Bizunesh M.; Bussche, Leen; Burvenich, Christian; Duchateau, Luc

    2013-01-01

    The mammary gland is an organ with a remarkable regenerative capacity that can undergo multiple cycles of proliferation, lactation, and involution. Growing evidence suggests that these changes are driven by the coordinated division and differentiation of mammary stem cell populations (MaSC). Whereas information regarding MaSC and their role in comparative mammary gland physiology is readily available in human and mice, such information remains scarce in most veterinary mammal species such as cows, horses, sheep, goats, pigs, and dogs. We believe that a better knowledge on the MaSC in these species will not only help to gain more insights into mammary gland (patho) physiology in veterinary medicine, but will also be of value for human medicine. Therefore, this review summarizes the current knowledge on stem cell isolation and characterization in different mammals of veterinary importance. PMID:23360296

  10. Nuclear cytomorphometry in feline mammary gland epithelial tumours.

    PubMed

    Simeonov, R; Simeonova, G

    2009-02-01

    Stained cytological specimens from 35 feline mammary gland epithelial tumours (4 adenomas, 11 tubulopapillary carcinomas 13 solid carcinomas and 7 cribriform carcinomas) were analysed by computer-assisted nuclear morphometry. In each case, the nuclei of at least 100 neoplastic cells were measured, and the mean nuclear area (MNA), mean nuclear perimeter (MNP), mean nuclear diameter (MND) and nuclear roundness (NR) were calculated. The study aimed to evaluate (1) the possibility of using nuclear cytomorphometry as an auxiliary diagnostic method to differentiate between benign and malignant feline mammary gland epithelial tumours, and (2) the prognostic value of nuclear morphometry in feline mammary carcinomas. The results indicated that MNA, MNP, MND and NR could be a useful adjunct in diagnosis but are not reliable prognostic indicators for feline mammary gland carcinomas.

  11. Vaginal myofibroblastoma with glands expressing mammary and prostatic antigens.

    PubMed

    Wallenfels, I; Chlumská, A

    2012-01-01

    A case of unusual vaginal myofibroblastoma containing glands which expressed mammary and prostatic markers is described. The tumor occurred in 70-year-old woman in the proximal third of the vagina. It showed morphology and immunophenotype typical of so-called cervicovaginal myofibroblastoma. The peripheral zone of the lesion contained a few groups of glands suggesting vaginal adenosis or prostatic-type glands on initial examination. The glands showed a surprising simultaneous expression of mammary markers mammaglobin and GCDFP-15 and prostatic markers prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP). Immunostains for alpha-smooth muscle actin, p63 and CD10 highlighted the myoepithelial cell layer of the glands. The finding indicates that simultaneous use of both mammary and prostatic markers for examination of unusual glandular lesions in the vulvovaginal location can be helpful for an exact diagnosis, and can contribute to better understanding of prostatic and mammary differentiations in the female lower genital tract.

  12. Notch in mammary gland development and breast cancer.

    PubMed

    Politi, Katerina; Feirt, Nikki; Kitajewski, Jan

    2004-10-01

    Notch signaling has been implicated in many processes including cell fate determination and oncogenesis. In mice, the Notch1 and Notch4 genes are both targets for insertion and rearrangement by the mouse mammary tumor virus and these mutations promote epithelial mammary tumorigenesis. Moreover, expression of a constitutively active form of Notch4 in mammary epithelial cells inhibits epithelial differentiation and leads to tumor formation in this organ. These data implicate the Notch pathway in breast tumorigenesis and provide the foundation for future experiments that will aid in our understanding of the role of Notch in human breast cancer development. Here, we review studies of mammary tumorigenesis induced by Notch in mouse and in vitro culture models providing evidence that Notch activation is a causal factor in human breast cancer.

  13. Serum neopterin levels in female dogs with malignant mammary tumours.

    PubMed

    Szczubiał, M; Dąbrowski, R; Łopuszyński, W

    2014-06-01

    In this study, we have determined serum neopterin levels in female dogs with primary malignant mammary tumours. The study involved 50 female dogs which had a malignant mammary tumours removed surgically (32 animals with carcinoma, 12 animals with sarcoma and 6 animals with carcinosarcoma) and 10 clinically healthy female dogs. Serum neopterin levels were determined using a commercial ELISA kit. The mean neopterin levels were lower in the malignant tumour groups than in healthy animals but differences were statistically significant only in carcinoma and sarcoma groups. The decrease of neopterin levels in animals with malignant mammary tumours may suggest their decreased cellular immunity. Moreover, it might indicate that decreased activity of cellular mechanisms of the anti-neoplastic response is one of the factors associated with the development and course of malignant mammary tumours in female dogs; however, further studies are necessary. © 2012 John Wiley & Sons Ltd.

  14. Developmental biology: cell fate in the mammary gland

    USDA-ARS?s Scientific Manuscript database

    Most breast cancers have their origin in the luminal epithelial cells of the mammary gland. Defining how a master regulator controls the development of this cell lineage could provide important hints about why this should be. ...

  15. Lessons Learned from Mouse Mammary Tumor Virus in Animal Models

    PubMed Central

    Dudley, Jaquelin P.; Golovkina, Tatyana V.; Ross, Susan R.

    2016-01-01

    Mouse mammary tumor virus (MMTV), which was discovered as a milk-transmitted, infectious, cancer-inducing agent in the 1930s, has been used as an animal model for the study of retroviral infection and transmission, antiviral immune responses, and breast cancer and lymphoma biology. The main target cells for MMTV infection in vivo are cells of the immune system and mammary epithelial cells. Although the host mounts an immune response to the virus, MMTV has evolved multiple means of evading this response. MMTV causes mammary tumors when the provirus integrates into the mammary epithelial and lymphoid cell genome during viral replication and thereby activates cellular oncogene expression. Thus, tumor induction is a by-product of the infection cycle. A number of important oncogenes have been discovered by carrying out MMTV integration site analysis, some of which may play a role in human breast cancer. PMID:27034391

  16. Genes affected by mouse mammary tumor virus (MMTV) proviral insertions in mouse mammary tumors are deregulated or mutated in primary human mammary tumors

    PubMed Central

    Callahan, Robert; Mudunuri, Uma; Bargo, Sharon; Raafat, Ahmed; McCurdy, David; Boulanger, Corinne; Lowther, William; Stephens, Robert; Luke, Brian T.; Stewart, Claudia; Wu, Xiaolin; Munroe, David; Smith, Gilbert H.

    2012-01-01

    The accumulation of mutations is a contributing factor in the initiation of premalignant mammary lesions and their progression to malignancy and metastasis. We have used a mouse model in which the carcinogen is the mouse mammary tumor virus (MMTV) which induces clonal premalignant mammary lesions and malignant mammary tumors by insertional mutagenesis. Identification of the genes and signaling pathways affected in MMTV-induced mouse mammary lesions provides a rationale for determining whether genetic alteration of the human orthologues of these genes/pathways may contribute to human breast carcinogenesis. A high-throughput platform for inverse PCR to identify MMTV-host junction fragments and their nucleotide sequences in a large panel of MMTV-induced lesions was developed. Validation of the genes affected by MMTV-insertion was carried out by microarray analysis. Common integration site (CIS) means that the gene was altered by an MMTV proviral insertion in at least two independent lesions arising in different hosts. Three of the new genes identified as CIS for MMTV were assayed for their capability to confer on HC11 mouse mammary epithelial cells the ability for invasion, anchorage independent growth and tumor development in nude mice. Analysis of MMTV induced mammary premalignant hyperplastic outgrowth (HOG) lines and mammary tumors led to the identification of CIS restricted to 35 loci. Within these loci members of the Wnt, Fgf and Rspo gene families plus two linked genes (Npm3 and Ddn) were frequently activated in tumors induced by MMTV. A second group of 15 CIS occur at a low frequency (2-5 observations) in mammary HOGs or tumors. In this latter group the expression of either Phf19 or Sdc2 was shown to increase HC11 cells invasion capability. Foxl1 expression conferred on HC11 cells the capability for anchorage-independent colony formation in soft agar and tumor development in nude mice. The published transcriptome and nucleotide sequence analysis of gene

  17. A mammary nodule mimicking breast cancer.

    PubMed

    Solaini, Leonardo; Bianchi, Anna; Filippini, Luigi; Lucini, Laura; Simoncini, Edda; Ragni, Fulvio

    2014-01-01

    Metastases to the breast from extramammary tumors are rare. Several clinical, radiologic, and histologic signs can help to distinguish metastases from breast primary tumors. In the present study, we present a case of a left-sided breast metastasis from renal cancer in a 44-year-old woman whose clinical presentation was a mammary nodule in the upper internal quadrant. The patient underwent quadrantectomy with sentinel lymph node biopsy. The histology revealed a clear cell carcinoma. On computed tomography scan a 5×8-cm left renal mass with pulmonary, liver, and intrapericardial nodules was found. The patient underwent palliative care and died after 4 months. Metastasis to the breast is rare, but all of those clinical, radiologic, and histologic signs more typical of extramammary malignancies should always be considered in order to choose the best treatment strategy.

  18. [Estrogen receptors and the mammary gland].

    PubMed

    Barrón, A; Bermejo, L; Castro, I

    1997-01-01

    For several decades it has been known that steroid hormones, estrogen and progesterone, regulate some genes involved in the growth, proliferation and differentiation of the mammary-gland in animals and humans. In the last years, the presence or absence of the nuclear estrogen receptor has been used by clinicians as a marker for tumor malignancy, as a prognostic index or as an important parameter for hormonal therapy with anti-estrogenic compounds of some hormone-dependent breast cancers. This review shows some advances in the knowledge of the structure, function, molecular mechanisms of estrogenic activity, and interaction with proteins like protooncogenes and growth factors. Also, we refer to the role of the estrogen receptor in the physiophatology of breast cancer.

  19. Milk protein concentrations in galactorrhoeic mammary secretions.

    PubMed

    Yap, P L; Pryde, E A; McClelland, D B

    1980-02-01

    Milk protein concentrations were determined either by double antibody radioimmunoassay (IgA) or single radial immunodiffusion (IgG, lactoferrin, lysozyme and albumin) in the mammayr secretions of one nulliparous and three parous female patients with galactorrhoea due to hyperprolactinaemia. Concentrations of all the proteins studied were found to be similar to the concentrations observed in post-partum colostrum. In particular, secretory IgA was the only form of IgA detected in galactorrhoeic secretions. It is suggested that hyperprolactinaemia alone can result in increased mammary synthesis of the milk proteins since the steroid changes associated with a full-term pregnancy and delivery of the placenta did not immediately precede the galactorrhoea in three of the four patients studied.

  20. Mitigation of ion-induced drift instability in electron plasma by a transverse current through the Landau-resonant layer

    NASA Astrophysics Data System (ADS)

    Kabantsev, A. A.; Driscoll, C. F.

    2016-10-01

    Experiments and theory on electron columns have characterized an algebraic damping of diocotron modes, caused by a flux of electrons through the resonance (critical) layer. This flux-driven damping also eliminates the ion-induced exponential instability of diocotron modes. Our plasmas rotate at rate ωE × B, and the (nominally stable) diocotron modes are described by amplitude Ad ,kz = 0 ,mθ = 1 , 2 , . . , frequency ωd(mθ) , and a wave/plasma critical radius rc(mθ) , where ωE × B(rc) =ωd/mθ mθ. External fields produce a low density (1/100) halo of electrons moving radially outward from the plasma core, with flux rate F ≡(- 1/-1Ne) dNe/dt) dNe dt. We find that algebraicdamping of the diocotron modes begins when the halo reaches the critical radius rc(mθ) , proceeding as Ad(Δt) =Ad(0) - γΔt , with γ = β(mθ) F . We also investigated the diocotron instability which occurs when a small number of ions are transiting the electron plasma. Dissimilar bounce-averaged drifts of electrons and ions polarize the diocotron mode density perturbations, developing instability analogous to the classical flute instability. The exponential growth rate Γ is proportional to the fractional neutralization (Ni/Ne) and to the separation between electrons and ions in the wave perturbation. We have found that the algebraic damping can suppress the exponential ion-induced instability only for amplitudes satisfying Ad <= βF/Γ. Supported by NSF Grant PHY-1414570, DOE Grants DE-SC0002451.

  1. Ion-induced effects on grain boundaries and a-Si:H tissue quality in microcrystalline silicon films

    SciTech Connect

    Bronneberg, A. C.; Cankoy, N.; Sanden, M. C. M. van de; Creatore, M.

    2012-11-15

    Microcrystalline silicon films have been deposited by means of the remote expanding thermal plasma. The effect of ion bombardment on the microcrystalline silicon film properties has been investigated by applying an RF bias to the deposition substrate. The application of the RF substrate bias resulted in the formation of an additional plasma in front of the substrate holder. Neither the SiH{sub 4} depletion nor the growth flux was significantly enhanced upon substrate biasing, which suggests that (the composition of) the growth precursor flux is unaffected and that the ion-film interaction mechanisms were responsible for the observed material changes. Moderate bias conditions (i.e., dc bias voltages up to {approx}70 V) led to an improved grain boundary passivation and densification of the amorphous silicon tissue, as concluded from the analysis of the infrared Si-H{sub x} stretching modes. These improvements have been ascribed to ion-induced Si surface atom displacement, which enhances the surface diffusion length of the growth precursors. More-energetic ion bombardment (i.e., under applied dc bias voltages of {approx}60 V and higher) resulted in enhanced (di)vacancy incorporation via ion-induced Si bulk atom displacement. The film crystallinity was found not to be affected by the ion bombardment, although a reduced crystallite size was observed under ion bombardment conditions where Si bulk displacement had been sufficiently activated. The extent of the ion-film interaction mechanism has been enhanced by increasing the ion-to-Si deposition flux ratio. Under specific ion bombardment conditions, i.e., dc bias voltage in the range of 40-70 V and ion/Si arrival rate {approx}0.20, microcrystalline silicon films have been obtained which, on the basis of the Si-H{sub x} stretching modes, are qualified as solar-grade, i.e., the intergranular space is filled with a dense amorphous silicon tissue which completely passivates the crystalline grain boundaries.

  2. Radiogenic neoplasia in thyroid and mammary clonogens

    SciTech Connect

    Clifton, K.H.

    1991-05-31

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process.

  3. Homebox Genes in Normal, Preneoplastic, and Neoplastic Mammary Glands.

    DTIC Science & Technology

    1998-01-01

    homeotic gene research in mammary gland biology. The general aim of this project has been to obtain a better and ultimately more clinically useful...biology. One such group of genes is the homeotic family, which act as transcription factors, switching on or off groups of genes that specify the details...potential to explore the role of homeotic genes in mammary development and in the etiology of cancer. These experiments cannot be done in humans, of

  4. Hippo pathway in mammary gland development and breast cancer.

    PubMed

    Shi, Peiguo; Feng, Jing; Chen, Ceshi

    2015-01-01

    Accumulated evidence suggests that the Hippo signaling pathway plays crucial roles in mammary gland development and breast cancer. Key components of the Hippo pathway regulate breast epithelial cell proliferation, migration, invasion, and stemness. Additionally, the Hippo pathway regulates breast tumor growth, metastasis, and drug resistance. It is expected that the Hippo pathway will provide novel therapeutic targets for breast cancer. This review will discuss and summarize the roles of several core components of the Hippo pathway in mammary gland development and breast cancer.

  5. Conserved and variable: Understanding mammary stem cells across species.

    PubMed

    Rauner, Gat; Ledet, Melissa M; Van de Walle, Gerlinde R

    2017-08-22

    Postnatal mammary gland development requires the presence of mammary stem and progenitor cells (MaSC), which give rise to functional milk-secreting cells and regenerate the mammary epithelium with each cycle of lactation. These long-lived, tissue-resident MaSC are also targets for malignant transformation and may be cancer cells-of-origin. Consequently, MaSC are extensively researched in relation to their role and function in development, tissue regeneration, lactation, and breast cancer. The basic structure and function of the mammary gland are conserved among all mammalian species, from the most primitive to the most evolved. However, species vary greatly in their lactation strategies and mammary cancer incidence, making MaSC an interesting focus for comparative research. MaSC have been characterized in mice, to a lesser degree in humans, and to an even lesser degree in few additional mammals. They remain uncharacterized in most mammalian species, including "ancient" monotremes, marsupials, wild, and rare species, as well as in common and domestic species such as cats. Identification and comparison of MaSC across a large variety of species, particularly those with extreme lactational adaptations or low mammary cancer incidence, is expected to deepen our understanding of development and malignancy in the mammary gland. Here, we review the current status of MaSC characterization across species, and underline species variations in lactation and mammary cancer through which we may learn about the role of MaSC in these processes. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  6. Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli

    PubMed Central

    Blum, Shlomo E.; Heller, Elimelech D.; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

    2015-01-01

    Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study

  7. Role of p53 Mammary Epithelial Cell Senescence

    DTIC Science & Technology

    2005-05-01

    susceptibility to oncogenesis exist in the normal mammary tissue, the milk -forming ducts of the mammary gland (for review [2]). Coupled with information...HMECs [25]. proportion of preselection HMECs [8]. The senescence associated with the ’selection’ phase in Human milk is an easily available source of...which has precluded their detailed biochemical proliferation at this stage is dependent on the pRb/p16 study [2,18]. Most of the work on milk cells has

  8. Mechanism of Environmental Carcinogen-Induced Mammary Tumorigenesis

    DTIC Science & Technology

    2001-10-01

    Detrick, Maryland 21702-5012. 13. ABSTRACT (Maximum 200 Words) Environmental pollutants such as polycyclic aromatic hydrocarbons ( PAH ) are believed to...of treatment of 7,12-dimethylbenz(a)anthracene (DMBA), a member of the PAH family. Estrogen is indispensable for the DMBA-mediated mammary...tumorigenesis. We hypothesize that DMBA-mediated rat mammary tumorigenesis involves in the activation of protooncogene Mdm2 which in turn negatively regulates

  9. Nonapoptotic Function of Caspase-6 in Promoting Mammary Carcinogenesis

    DTIC Science & Technology

    2012-01-01

    Figure 4), normal human mammary tissues show little caspase-6 staining and about 60% of cancer tissues showed strong caspase-6 staining (Figure 4...Center) were stained for caspse-6. The included one of the three normal mammary tissues (upper panels) contains little caspase-6 staining . The cancer...lower panel) is highly positive of caspse-6 staining . A 100X magnification (left panels) and a 400X magnification are shown. About 60% of

  10. Comparative analysis of Fe ion-induced mutations in murine tissue and cells

    NASA Astrophysics Data System (ADS)

    Kronenberg, A.; Gauny, S.; Kwoh, E.; Dan, C.; Connolly, L.; Turker, M.

    Space flight exposes astronauts to densely ionizing heavy ions including Fe ions This study is designed to assess the impact of the tissue microenvironment on the cytotoxic and mutagenic effects of 1 GeV amu Fe ions in kidney epithelial cells from one mouse strain irradiated either in vitro or in vivo Three to five month old Aprt heterozygous mice are used from a C57BL6 DBA2 cross B6D2F1 or kidney cells are used that were established from these mice Cells and animals were exposed in the plateau portion of the Bragg peak 159 keV mu m at the NASA Space Radiation Laboratories NSRL at Brookhaven National Laboratory Approximately equal numbers of male and female animals were used for the in vivo studies In vitro experiments demonstrated exponential cell killing with a D 0 of 92 cGy Three Aprt mutation experiments have been performed in kidney cells exposed to graded doses of Fe ions in vitro 0-2 Gy Studies to date indicate that Fe ions are mutagenic to kidney epithelial cells irradiated in vitro with a linear induction of mutants as a function of dose In vivo experiments have been completed on two thirds of the animals planned for the study Kidney cells were retrieved from the animals at two time points 2-3 months post-irradiation or 8-9 months post-irradiation Fe ion exposure in vivo led to exponential killing of kidney epithelial cells that was still evident 8-9 months post-exposure In vivo irradiation also results

  11. The role of tight junctions in mammary gland function.

    PubMed

    Stelwagen, Kerst; Singh, Kuljeet

    2014-03-01

    Tight junctions (TJ) are cellular structures that facilitate cell-cell communication and are important in maintaining the three-dimensional structure of epithelia. It is only during the last two decades that the molecular make-up of TJ is becoming unravelled, with two major transmembrane-spanning structural protein families, called occludin and claudins, being the true constituents of the TJ. These TJ proteins are linked via specific scaffolding proteins to the cell's cytoskeleton. In the mammary gland TJ between adjacent secretory epithelial cells are formed during lactogenesis and are instrumental in establishing and maintaining milk synthesis and secretion, whereas TJ integrity is compromised during mammary involution and also as result of mastitis and periods of mammary inflamation (including mastitis). They prevent the paracellular transport of ions and small molecules between the blood and milk compartments. Formation of intact TJ at the start of lactation is important for the establishment of the lactation. Conversely, loss of TJ integrity has been linked to reduced milk secretion and mammary function and increased paracellular transport of blood components into the milk and vice versa. In addition to acting as a paracellular barrier, the TJ is increasingly linked to playing an active role in intracellular signalling. This review focusses on the role of TJ in mammary function of the normal, non-malignant mammary gland, predominantly in ruminants, the major dairy producing species.

  12. Internal mammary node management in breast cancer. A review.

    PubMed

    Vrana, David; Gatek, Jiri; Cwiertka, Karel; Lukesova, Lucie; Koranda, Pavel

    2013-09-01

    Internal mammary nodes visualized during sentinel node biopsy for breast cancer, remain an unresolved management issue. Further, both internal mammary node (IMN) radiotherapy and biopsy have attendant risks and hence should be used with caution. The purpose of this review is to highlight the available data and evidence. A PubMed database from 1960 to 2012 using key words: internal mammary nodes, breast cancer radiotherapy planning, adjuvant radiotherapy, sentinel node biopsy in breast cancer and selected publications on the significance of internal mammary nodes in breast cancer treatment, published data and approaches used. We found 14513 relevant papers and we selected 30 that clearly investigated the management of internal mammary nodes during sentinel node search. We focused on the incidence of IMN metastasis (6 papers), risk factors associated with IMN drainage (9 reports), management of IMN and the impact on disease free and overall patient survival (15 papers). The evidence for breast cancer axillary nodes management is good but the data for other draining nodes such as internal mammary nodes are far less conclusive and further research is needed.

  13. Immunohistochemical characterization of mammary squamous cell carcinoma of the dog.

    PubMed

    Sassi, Francesco; Sarli, Giuseppe; Brunetti, Barbara; Morandi, Federico; Benazzi, Cinzia

    2008-11-01

    Squamous cell carcinoma of the mammary gland is rare in both veterinary and human medicine. Whereas human metaplastic and squamous variants are known, the objectives of the current study were to ascertain the presence of such entities in canine mammary tumors and to distinguish them from other (epidermal, sweat gland) squamous tumors that may develop in the same area. A panel of antibodies (anti-cytokeratin [CK] 19, CK 14, CK 5/6, pancytokeratin, and vimentin) was used on 18 mammary gland malignancies with squamous features and 16 malignant skin tumors (11 squamous cell carcinomas of the skin and 5 sweat glands). Fifteen of the 18 mammary carcinomas were classified as metaplastic carcinomas, and the remaining 3 were classified as squamous cell carcinomas. The 2 most useful markers to establish the histogenesis of mammary tumors were pancytokeratin and CK 19. All other antibodies were equally expressed (CK 14 and 5/6) in all histotypes. The antibody panel discriminated primary epidermal squamous tumors (pancytokeratin positive and CK 19 negative) from gland-derived squamous neoplasms (pancytokeratin positive and CK 19 positive) but failed to distinguish primary mammary tumors from other squamous tumors of glandular origin.

  14. Soy isoflavones increase latency of spontaneous mammary tumors in mice.

    PubMed

    Jin, Zeming; MacDonald, Ruth S

    2002-10-01

    Soy protein, with and without isoflavones, is being added to foods by manufacturers in response to the Food and Drug Administration (FDA)-approved health claim for cardiovascular protection. Furthermore, soy isoflavones are increasingly consumed by women in the United States as an alternative to hormone replacement therapy. The role of these phytoestrogens in breast cancer is controversial. Although exposure of rodents to soy isoflavones during the perinatal period appears to reduce mammary cancer formation, exposure in utero or during adulthood may increase tumor growth. The mouse mammary tumor virus (MMTV)-neu mouse spontaneously develops mammary tumors due to overexpression of the ErbB-2/neu/HER2 oncogene. This model is comparable with human breast cancer because overexpression of the neu oncogene occurs in 20-40% of human breast cancers. We fed MMTV-neu mice AIN-93G diets containing no isoflavones, 250 mg/kg genistein, 250 mg/kg daidzein or an isoflavone mixture (NovaSoy, equivalent to 250 mg genistein/kg) from 7 wk of age. Mammary tumor latency was significantly delayed in mice fed isoflavones compared with the control. Once tumors formed, however, the isoflavones did not reduce the number or size of tumors such that at 34 wk of age there were no differences in tumor burden among the treatment groups. Hence, in the MMTV-neu mouse, soy isoflavones delayed mammary tumorigenesis. Further studies are warranted to define the cellular mechanisms through which these compounds affect mammary tumorigenesis in this model.

  15. Mammary hypoplasia: not every breast can produce sufficient milk.

    PubMed

    Arbour, Megan W; Kessler, Julia Lange

    2013-01-01

    Breast milk is considered the optimal form of nutrition for newborn infants. Current recommendations are to breastfeed for 6 months. Not all women are able to breastfeed. Mammary hypoplasia is a primary cause of failed lactogenesis II, whereby the mother is unable to produce an adequate milk volume. Women with mammary hypoplasia often have normal hormone levels and innervation but lack sufficient glandular tissue to produce an adequate milk supply to sustain their infant. The etiology of this rare condition is unclear, although there are theories that refer to genetic predisposition and estrogenic environmental exposures in select agricultural environments. Women with mammary hypoplasia may not exhibit the typical breast changes associated with pregnancy and may fail to lactate postpartum. Breasts of women with mammary hypoplasia may be widely spaced (1.5 inches or greater), asymmetric, or tuberous in nature. Awareness of the history and clinical signs of mammary hypoplasia during the prenatal period and immediate postpartum increases the likelihood that women will receive the needed education and physical and emotional support and encouragement. Several medications and herbs demonstrate some efficacy in increasing breast milk production in women with mammary hypoplasia.

  16. Mast cells in canine cutaneous hemangioma, hemangiosarcoma and mammary tumors.

    PubMed

    Woldemeskel, Moges; Rajeev, Sreekumari

    2010-02-01

    Mast cell count (MCC) in 45 dogs with cutaneous hemangioma (HA, n = 12), hemangiosarcoma (HSA, n = 12), mammary adenoma (AD, n = 9) and mammary adenocarcinoma (AC, n = 12) was made using Toluidine blue stained sections. Antibodies against endothelial cell markers, Factor VIII and VEGF were used to visualize and determine the hot spot micro-vessel density (MVD). Total MCC and MCC along the invasive edges were significantly higher (p < 0.001) in canine mammary AC than in AD. The total MCC did not significantly differ (p > 0.05), in HSAs (8.6 +/- 3.3) than in HAs (5.5 +/- 2.8). There is a positive correlation (r = 0.14) between the hot spot MCC and MVD in mammary AC, although not significant (p = 0.3172), indicating that mast cells are associated with angiogenesis in canine mammary AC. This study suggests that mast cells may play an important role in neovascularization of canine cutaneous vascular and mammary neoplasms. Detailed studies encompassing correlation of MCC and MVD with clinical outcomes and prognosis in these neoplasms are recommended.

  17. Technical note: Isolation and characterization of porcine mammary epithelial cells.

    PubMed

    Dahanayaka, S; Rezaei, R; Porter, W W; Johnson, G A; Burghardt, R C; Bazer, F W; Hou, Y Q; Wu, Z L; Wu, G

    2015-11-01

    Within the mammary gland, functional synthesis of milk is performed by its epithelial (alveolar) cells. The availability of a stable mammary epithelial cell line is essential for biochemical studies to elucidate cellular and molecular mechanisms responsible for nutritional regulation of lactation. Therefore, porcine mammary epithelial cells (PMEC) were isolated from mammary glands of a 9-mo-old nonpregnant and nonlactating gilt and cultured to establish a nonimmortalized cell line. These cells were characterized by expression of cytokeratin-18 (an intermediate filament specific for epithelial cells), β-casein (a specific marker for mammary epithelial cells), and α-lactalbumin. In culture, the PMEC doubled in number every 24 h and maintained a cobblestone morphology, typical for cultured epithelial cells, for at least 15 passages. Addition of 0.2 to 2 μg/mL prolactin to culture medium for 3 d induced the production of β-casein and α-lactalbumin by PMEC in a dose-dependent manner. Thus, we have successfully developed a useful PMEC line for future studies of cellular and molecular regulation of milk synthesis by mammary epithelial cells of the sow.

  18. TCDD exposure disrupts mammary epithelial cell differentiation and function

    PubMed Central

    Collins, Loretta L.; Lew, Betina J.; Lawrence, B. Paige

    2011-01-01

    Mammary gland growth and differentiation during pregnancy is a developmental process that is sensitive to the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is a widespread environmental contaminant and a potent ligand for the aryl hydrocarbon receptor (AhR). We demonstrate reduced β-casein protein induction in mouse mammary glands and in cultured SCp2 mammary epithelial cells following exposure to TCDD. SCp2 cells exposed to TCDD also show reduced cell clustering and less alveolar-like structure formation. SCp2 cells express transcriptionally active AhR, and exposure to TCDD induces expression of the AhR target gene CYP1B1. Exposure to TCDD during pregnancy reduced expression of the cell adhesion molecule E-cadherin in the mammary gland and decreased phosphorylation of STAT5, a known regulator of β-casein gene expression. These data provide morphological and molecular evidence that TCDD-mediated AhR activation disrupts structural and functional differentiation of the mammary gland, and present an in vitro model for studying the effects of TCDD on mammary epithelial cell function. PMID:19490989

  19. Mutation Induction in Mammalian Cells by Accelerated Heavy Ions

    NASA Astrophysics Data System (ADS)

    Rosendahl, I. M.; Baumstark-Khan, C.; Rink, H.

    The deleterious effects of accelerated heavy ions on living cells are of increasing importance for long duration human space flight activities. An important aspect of this field is attributed to the type and quality of biological damage induced by these densely ionizing particles. To address this aspect, cell inactivation and mutation induction at the hprt locus (coding for hypoxanthine-guanine-phosphoribosyl-transferase) was investigated in cultured V79 Chinese Hamster Cells irradiated with accelerated heavy ions (8-O, 20-Ca, 79-Au, and 92-U) and X-rays. Specific energies of the ions ranged from 1.9 to 69.7 MeV/u and corresponding LET values were between 62 band 15,580 keV/μ m. 30 spontaneous and 196 heavy-ion induced 6-thioguanine resistant hprt mutant colonies were characterized by Southern technique using the restriction enzymes EcoRI, PstI and BglII and a full length hprt cDNA probe isolated from the plasmid pHpt12 (kindly provided by Dr. J. Thacker). While inactivation cross sections (σ i) rise over the whole LET range, mutation induction cross sections (σ m) increase up to approximately 300 keV/μ m (O-ions) but decline with heavier ions and more extreme LET values. A similar behaviour is seen with mutation frequency dependent on particle fluence. After irradiation with accelerated uranium ions (8.8 MeV/u, 15,580 keV/μ m) a significant decrease of mutation frequency was found with higher particle fluences (3× 106 particles cm-2). Nearly no mutants were recovered with 8× 106 particles cm-2. All restriction patterns of the spontaneous hprt mutants were indistinguishable from the wild type pattern. These mutants probably contain small deletions or point mutations in the hprt locus. In contrast, the overall spectrum of heavy ion induced mutations revealed a majority (67%) of partial or complete deletions of the hprt gene. With constant particle fluence (3× 106 particles cm-2) the quality of heavy ion induced mutations in the hprt locus depends on physical

  20. Characterization and ion-induced degradation of cross-linked poly(methyl methacrylate) studied using time of flight secondary ion mass spectrometry

    NASA Astrophysics Data System (ADS)

    Wagner, M. S.; Lenghaus, K.; Gillen, G.; Tarlov, M. J.

    2006-12-01

    In this study, a series of random copolymers of methyl methacrylate (MMA) and ethylene glycol dimethacrylate (EGDMA) were prepared as surface-initiated polymer (SIP) films on silicon substrates using atom transfer radical polymerization. Positive and negative ion static time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to characterize SIP films with different MMA/EGDMA monomer ratios in an attempt to quantify their surface composition. However, matrix effects in the positive and negative ion modes led to preferential secondary ion generation from the EGDMA monomer and suppression of secondary ions characteristic of the MMA monomer, precluding accurate quantification using standard linear quantification methods. Ion-induced degradation of these films under 5 keV SF 5+ bombardment was also examined to determine the effect of cross-linking on the accumulation of ion-induced damage. Increasing incorporation of the EGDMA cross-linker in the SIP films decreased the sputter rate and increased the rate of damage accumulation under extended (>10 14 ions/cm 2) 5 keV SF 5+ bombardment. Comparison of the ion bombardment data with thermal degradation of cross-linked PMMA suggests that the presence of the cross-linker impedes degradation by depolymerization, resulting in ion-induced damage accumulation. The increased rate of ion-induced damage accumulation with increased cross-link density also suggests that polymers that can form cross-links during ion bombardment are less amenable to depth profiling using polyatomic primary ions.

  1. Ion-induced synthesis of uniform single-crystalline sulphide-based quaternary-alloy hexagonal nanorings for highly efficient photocatalytic hydrogen evolution.

    PubMed

    Hu, Peng; Pramana, Stevin Snellius; Cao, Shaowen; Ngaw, Chee Keong; Lin, Jingdong; Loo, Say Chye Joachim; Tan, Timothy Thatt Yang

    2013-05-14

    Uniform single-crystalline quaternary sulphide nanoring photocatalysts are synthesized via the copper-ion-induced Kirkendall effect and is followed by a cation exchange reaction. The obtained Cu(2+)-doped ZnIn(2)S(4) nanorings show highly preserved morphology, and demonstrate high visible-light-driven photocatalytic activity for H(2) evolution in water splitting.

  2. Scanning picosecond tunable laser system for simulating MeV heavy ion-induced charge collection events as a function of temperature.

    PubMed

    Laird, Jamie Stuart; Chen, Yuan; Scheick, Leif; Vo, Tuan; Johnston, Allan

    2008-08-01

    A new methodology for using scanning picosecond laser microscopy to simulate cosmic ray induced radiation effects as a function of temperature is described in detail. The built system is centered on diffraction-limited focusing of the output from a broadband (690-960 nm) ultrafast Ti:sapphire Tsunami laser pumped by a 532 nm Millennia laser. An acousto-optic modulator is used to provide pulse picking down to event rates necessary for the technologies and effects under study. The temperature dependence of the charge generation process for ions and photons is briefly reviewed and the need for wavelength tunability is discussed. An appropriate wavelength selection is critical for proper emulation of ion events over a wide temperature range. The system developed is detailed and illustrated by way of example on a deep-submicron complementary metal-oxide semiconductor test structure.

  3. Fractal and multifractal characteristics of swift heavy ion induced self-affine nanostructured BaF{sub 2} thin film surfaces

    SciTech Connect

    Yadav, R. P.; Mittal, A. K.; Kumar, Manvendra Pandey, A. C.

    2015-08-15

    Fractal and multifractal characteristics of self-affine surfaces of BaF{sub 2} thin films, deposited on crystalline Si 〈1 1 1〉 substrate at room temperature, were studied. Self-affine surfaces were prepared by irradiation of 120 MeV Ag{sup 9+} ions which modified the surface morphology at nanometer scale. The surface morphology of virgin thin film and those irradiated with different ion fluences are characterized by atomic force microscopy technique. The surface roughness (interface width) shows monotonic decrease with ion fluences, while the other parameters, such as lateral correlation length, roughness exponent, and fractal dimension, did not show either monotonic decrease or increase in nature. The self-affine nature of the films is further confirmed by autocorrelation function. The power spectral density of thin films surfaces exhibits inverse power law variation with spatial frequency, suggesting the existence of fractal component in surface morphology. The multifractal detrended fluctuation analysis based on the partition function approach is also performed on virgin and irradiated thin films. It is found that the partition function exhibits the power law behavior with the segment size. Moreover, it is also seen that the scaling exponents vary nonlinearly with the moment, thereby exhibiting the multifractal nature.

  4. Energy scaling of the ion-induced desorption yield for perpendicular collisions of Ar and U with stainless steel in the energy range of 5 and 100 MeV/u

    SciTech Connect

    Kollmus, H.; Kraemer, A.; Bender, M.; Bellachioma, M. C.; Reich-Sprenger, H.; Mahner, E.; Hedlund, E.; Westerberg, L.; Malyshev, O. B.; Leandersson, M.; Edqvist, E.

    2009-03-15

    For the GSI future project Facility for Antiproton and Ion Research a beam intensity of 10{sup 12} U{sup 28+}ions/s is planned to be extracted from the GSI heavy ion synchrotron SIS18. Measurements performed in 2001 showed that the beam lifetime of the ions in the synchrotron is decreasing with increasing number of injected particles due to vacuum instabilities caused by ion-induced desorption. The injection energy for the SIS18 is about 10 MeV/u and U{sup 28+} ions are accelerated to 200 MeV/u limited by the magnetic rigidity for the low charge state. The aim of this work was to measure the desorption yield as a function of the impact energy from injection to extraction of SIS18 at GSI. Low energy yields at 5.0, 9.7, and 17.7 MeV/u were measured at the Cyclotron of The Svedberg Laboratory in Uppsala. High energy yields at 40, 80, and 100 MeV/u were measured at SIS18 of GSI in a different setup. It was found that the desorption yield scales with the electronic energy loss (dE/dx){sub el}{sup n}, with n between 2 and 3, decreasing for increasing impact energy above the Bragg maximum.

  5. Mammary sensitivity to protein restriction and re-alimentation.

    PubMed

    Goodwill, M G; Jessop, N S; Oldham, J D

    1996-09-01

    The present study tested the influence of protein undernutrition and re-alimentation on mammary gland size and secretory cell activity in lactating rats. During gestation, female Sprague-Dawley rats were offered a high-protein diet (215 g crude protein (N x 6.25; CP)/kg DM; H); litters were standardized to twelve pups at parturition. During lactation, two diets were offered ad libitum, diet H and a low-protein diet (90 g CP/kg DM; L). Lactational dietary treatments were the supply ad libitum of either diet H (HHH) or diet L (LLL) for the first 12 d of lactation, or diet L transferring to diet H on either day 6 (LHH) or 9 (LLH) of lactation. On days 1, 6, 9 and 12 of lactation, rats from each group (n > or = 6) were used to estimate mammary dry mass, fat, protein, DNA and RNA; the activities of lactose synthetase (EC 2.4.1.22) enzyme and Na+,K(+)-ATPase (EC 3.6.1.37) were also measured. Rats offered a diet considered protein sufficient (H) from day 1 of lactation showed a decrease in mammary dry mass and fat but an increase in DNA, RNA and protein on day 6, after which there was no further change, except for mammary protein which continued to increase. However, rats offered diet L showed a steady loss in mammary mass and fat throughout the 12 d lactation period and no change in mammary DNA, RNA or protein. Rats previously protein restricted for either the first 6 or 9 d of lactation had their mammary dry mass and mammary fat loss halted and showed a rapid increase in mammary DNA, RNA and protein on re-alimentation. Lactose production in group HHH, as measured by lactose synthetase activity, was similar on days 1 and 6 of lactation, after which a significant increase was seen. Protein-restricted rats showed no change in lactose synthetase activity during the 12 d experimental period. Changing from diet L to diet H led to a significant increase in lactose synthetase activity to levels comparable with those offered diet H from day 1. These results show that rats

  6. Social isolation induces autophagy in the mouse mammary gland: link to increased mammary cancer risk.

    PubMed

    Sumis, Allison; Cook, Katherine L; Andrade, Fabia O; Hu, Rong; Kidney, Emma; Zhang, Xiyuan; Kim, Dominic; Carney, Elissa; Nguyen, Nguyen; Yu, Wei; Bouker, Kerrie B; Cruz, Idalia; Clarke, Robert; Hilakivi-Clarke, Leena

    2016-10-01

    Social isolation is a strong predictor of early all-cause mortality and consistently increases breast cancer risk in both women and animal models. Because social isolation increases body weight, we compared its effects to those caused by a consumption of obesity-inducing diet (OID) in C57BL/6 mice. Social isolation and OID impaired insulin and glucose sensitivity. In socially isolated, OID-fed mice (I-OID), insulin resistance was linked to reduced Pparg expression and increased neuropeptide Y levels, but in group-housed OID fed mice (G-OID), it was linked to increased leptin and reduced adiponectin levels, indicating that the pathways leading to insulin resistance are different. Carcinogen-induced mammary tumorigenesis was significantly higher in I-OID mice than in the other groups, but cancer risk was also increased in socially isolated, control diet-fed mice (I-C) and G-OID mice compared with that in controls. Unfolded protein response (UPR) signaling (GRP78; IRE1) was upregulated in the mammary glands of OID-fed mice, but not in control diet-fed, socially isolated I-C mice. In contrast, expression of BECLIN1, ATG7 and LC3II were increased, and p62 was downregulated by social isolation, indicating increased autophagy. In the mammary glands of socially isolated mice, but not in G-OID mice, mRNA expressions of p53 and the p53-regulated autophagy inducer Dram1 were upregulated, and nuclear p53 staining was strong. Our findings further indicated that autophagy and tumorigenesis were not increased in Atg7(+/-) mice kept in social isolation and fed OID. Thus, social isolation may increase breast cancer risk by inducing autophagy, independent of changes in body weight.

  7. Metabotropic glutamate receptor 1 disrupts mammary acinar architecture and initiates malignant transformation of mammary epithelial cells

    PubMed Central

    Teh, Jessica L. F.; Shah, Raj; La Cava, Stephanie; Dolfi, Sonia C.; Mehta, Madhura S.; Kongara, Sameera; Price, Sandy; Ganesan, Shridar; Reuhl, Kenneth R.; Hirshfield, Kim M.

    2016-01-01

    Metabotropic glutamate receptor 1 (mGluR1/Grm1) is a member of the G-protein-coupled receptor superfamily, which was once thought to only participate in synaptic transmission and neuronal excitability, but has more recently been implicated in non-neuronal tissue functions. We previously described the oncogenic properties of Grm1 in cultured melanocytes in vitro and in spontaneous melanoma development with 100 % penetrance in vivo. Aberrant mGluR1 expression was detected in 60–80 % of human melanoma cell lines and biopsy samples. As most human cancers are of epithelial origin, we utilized immortalized mouse mammary epithelial cells (iMMECs) as a model system to study the transformative properties of Grm1. We introduced Grm1 into iMMECs and isolated several stable mGluR1-expressing clones. Phenotypic alterations in mammary acinar architecture were assessed using three-dimensional morphogenesis assays. We found that mGluR1-expressing iMMECs exhibited delayed lumen formation in association with decreased central acinar cell death, disrupted cell polarity, and a dramatic increase in the activation of the mitogen-activated protein kinase pathway. Orthotopic implantation of mGluR1-expressing iMMEC clones into mammary fat pads of immunodeficient nude mice resulted in mammary tumor formation in vivo. Persistent mGluR1 expression was required for the maintenance of the tumorigenic phenotypes in vitro and in vivo, as demonstrated by an inducible Grm1-silencing RNA system. Furthermore, mGluR1 was found be expressed in human breast cancer cell lines and breast tumor biopsies. Elevated levels of extracellular glutamate were observed in mGluR1-expressing breast cancer cell lines and concurrent treatment of MCF7 xenografts with glutamate release inhibitor, riluzole, and an AKT inhibitor led to suppression of tumor progression. Our results are likely relevant to human breast cancer, highlighting a putative role of mGluR1 in the pathophysiology of breast cancer and the potential

  8. Differential transformation of mammary epithelial cells by Wnt genes.

    PubMed Central

    Wong, G T; Gavin, B J; McMahon, A P

    1994-01-01

    The mouse Wnt family includes at least 10 genes that encode structurally related secreted glycoproteins. Wnt-1 and Wnt-3 were originally identified as oncogenes activated by the insertion of mouse mammary tumor virus in virus-induced mammary adenocarcinomas, although they are not expressed in the normal mammary gland. However, five other Wnt genes are differentially expressed during development of adult mammary tissue, suggesting that they may play distinct roles in various phases of mammary gland growth and development. Induction of transformation by Wnt-1 and Wnt-3 may be due to interference with these normal regulatory events; however, there is no direct evidence for this hypothesis. We have tested Wnt family members for the ability to induce transformation of cultured mammary cells. The results demonstrate that the Wnt gene family can be divided into three groups depending on their ability to induce morphological transformation and altered growth characteristics of the C57MG mammary epithelial cell line. Wnt-1, Wnt-3A, and Wnt-7A were highly transforming and induced colonies which formed and shed balls of cells. Wnt-2, Wnt-5B, and Wnt-7B also induced transformation but with a lower frequency and an apparent decrease in saturation density. In contrast, Wnt-6 and two other family members which are normally expressed in C57MG cells, Wnt-4 and Wnt-5A, failed to induce transformation. These data demonstrate that the Wnt genes have distinct effects on cell growth and should not be regarded as functionally equivalent. Images PMID:8065359

  9. Specific posttranslational modification regulates early events in mammary carcinoma formation.

    PubMed

    Guo, Hua-Bei; Johnson, Heather; Randolph, Matthew; Nagy, Tamas; Blalock, Ryan; Pierce, Michael

    2010-12-07

    The expression of an enzyme, GnT-V, that catalyzes a specific posttranslational modification of a family of glycoproteins, namely a branched N-glycan, is transcriptionally up-regulated during breast carcinoma oncogenesis. To determine the molecular basis of how early events in breast carcinoma formation are regulated by GnT-V, we studied both the early stages of mammary tumor formation by using 3D cell culture and a her-2 transgenic mouse mammary tumor model. Overexpression of GnT-V in MCF-10A mammary epithelial cells in 3D culture disrupted acinar morphogenesis with impaired hollow lumen formation, an early characteristic of mammary neoplastic transformation. The disrupted acinar morphogenesis of mammary tumor cells in 3D culture caused by her-2 expression was reversed in tumors that lacked GnT-V expression. Moreover, her-2-induced mammary tumor onset was significantly delayed in the GnT-V null tumors, evidence that the lack of the posttranslational modification catalyzed by GnT-V attenuated tumor formation. Inhibited activation of both PKB and ERK signaling pathways was observed in GnT-V null tumor cells. The proportion of tumor-initiating cells (TICs) in the mammary tumors from GnT-V null mice was significantly reduced compared with controls, and GnT-V null TICs displayed a reduced ability to form secondary tumors in NOD/SCID mice. These results demonstrate that GnT-V expression and its branched glycan products effectively modulate her-2-mediated signaling pathways that, in turn, regulate the relative proportion of tumor initiating cells and the latency of her-2-driven tumor onset.

  10. Neuropilin-2 promotes branching morphogenesis in the mouse mammary gland.

    PubMed

    Goel, Hira Lal; Bae, Donggoo; Pursell, Bryan; Gouvin, Lindsey M; Lu, Shaolei; Mercurio, Arthur M

    2011-07-01

    Although the neuropilins were characterized as semaphorin receptors that regulate axon guidance, they also function as vascular endothelial growth factor (VEGF) receptors and contribute to the development of other tissues. Here, we assessed the role of NRP2 in mouse mammary gland development based on our observation that NRP2 is expressed preferentially in the terminal end buds of developing glands. A floxed NRP2 mouse was bred with an MMTV-Cre strain to generate a mammary gland-specific knockout of NRP2. MMTV-Cre;NRP2(loxP/loxP) mice exhibited significant defects in branching morphogenesis and ductal outgrowth compared with either littermate MMTV-Cre;NRP2(+/loxP) or MMTV-Cre mice. Mechanistic insight into this morphological defect was obtained from a mouse mammary cell line in which we observed that VEGF(165), an NRP2 ligand, induces branching morphogenesis in 3D cultures and that branching is dependent upon NRP2 as shown using shRNAs and a function-blocking antibody. Epithelial cells in the mouse mammary gland express VEGF, supporting the hypothesis that this NRP2 ligand contributes to mammary gland morphogenesis. Importantly, we demonstrate that VEGF and NRP2 activate focal adhesion kinase (FAK) and promote FAK-dependent branching morphogenesis in vitro. The significance of this mechanism is substantiated by our finding that FAK activation is diminished significantly in developing MMTV-Cre;NRP2(loxP/loxP) mammary glands compared with control glands. Together, our data reveal a VEGF/NRP2/FAK signaling axis that is important for branching morphogenesis and mammary gland development. In a broader context, our data support an emerging hypothesis that directional outgrowth and branching morphogenesis in a variety of tissues are influenced by signals that were identified initially for their role in axon guidance.

  11. HORMONAL INFLUENCES ON MAMMARY TUMORS OF THE RAT

    PubMed Central

    Huggins, Charles; Mainzer, Klaus

    1957-01-01

    Many members of the androstane series profoundly retarded the growth of a transplanted benign mammary fibroadenoma of the rat; the restraint of tumor growth was in direct proportion to the amount of the administered compound until its maximal effect was achieved. Certain steroids closely related to the androstane inhibitors accelerated the growth of the tumor. These effects of divergent sort depend on the molecular structure of the steroid. The molecular structure of androstane derivatives, which is of high significance in modifying the rate of growth of the benign mammary tumor, consists of multiple components. These include (a) the presence and number of ketone and hydroxyl groups in special orientation at specific sites, (b) the sites of dehydrogenation in the molecule, and (c) the presence, number, and state of hydrogenation of alkyl groups at designated molecular positions. These multiple factors determine whether androstane compounds will inhibit growth of the tumor, enhance it, or fail to influence its growth. The androstane compounds which caused either the restraint or the promotion of tumor growth had the common property of inducing proliferation of the normal mammary epithelium. Two mechanisms are involved in the restraint of growth of mammary fibroadenoma by androstane inhibitors. The primary effect is the abolition of action of phenolic estrogens and progesterone when dihydrotestosterone is administered concurrently, presumably through direct action at the tumor cell level A secondary contributory suppressive effect is the depression of ovarian activity, and consequently of the production of phenolic estrogens and progesterone, by these compounds. Transplanted mammary fibroadenoma in the rat possesses neoplastic traits and also some growth properties of normal mammary epithelium; inhibition of these latter by hormonal methods commonly retarded the growth of the tumor. But in hypophysectomized rats dihydrotestosterone failed to inhibit the growth of a

  12. Endocrine-active chemicals in mammary cancer causation and prevention.

    PubMed

    Jenkins, Sarah; Betancourt, Angela M; Wang, Jun; Lamartiniere, Coral A

    2012-04-01

    Endocrine-active chemicals alter or mimic physiological hormones. These compounds are reported to originate from a wide variety of sources, and recent studies have shown widespread human exposure to several of these compounds. Given the role of the sex steroid hormone, estradiol, in human breast cancer causation, endocrine-active chemicals which interfere with estrogen signaling constitute one potential factor contributing to the high incidence of breast cancer. Thus, the aim of this review is to examine several common endocrine-active chemicals and their respective roles in breast cancer causation or prevention. The plastic component, bisphenol A (BPA), the synthetic estrogen, diethylstilbestrol (DES), the by-product of organic combustion, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the soy component, genistein, and the red grape phytoalexin, resveratrol, have some degree of structural similarities to each other and estradiol. However, despite these structural similarities, the in vitro and in vivo properties of each of these chemicals vary greatly in terms of breast cancer causation and prevention. Early life exposure to BPA and DES increases rodent susceptibility to chemically induced mammary carcinogenesis, presumably through retardation of normal mammary gland maturation and/or disrupting the ratio of cell proliferation and apoptosis in the mammary gland. On the other hand, early exposures to genistein and resveratrol protect rodents against chemically induced and spontaneous mammary cancers. This is reported to occur through the ability of genistein and resveratrol to accelerate mammary gland maturation. Interestingly, TCDD, which is the most structurally dissimilar to the above chemicals and functions as an anti-estrogen, also increases chemically induced mammary carcinogenesis through retardation of mammary gland maturation. This article is part of a Special Issue entitled 'Endocrine disruptors'. Copyright © 2011. Published by Elsevier Ltd.

  13. Burnout thresholds and cross section of power MOS transistors with heavy ions. Technical report, 1 May 1986-30 April 1988

    SciTech Connect

    Waskiewicz, A.E.; Groninger, J.W.

    1990-02-01

    Power MOSFET heavy ion-induced Single Event Burnout tests were performed jointly by representatives of the Aerospace Corporation, NASA Goddard, NWSC Crane and Rockwell International. For the most part, presented are the results of the burnout threshold and cross section characterizations performed on n-channel power MOSFETs, however a small amount of p-channel data is also included. In addition, data on the effect of temperature, gate bias, total dose and inductive loading on MOSFET Single Event Burnout sensitivity is preferred. At the time of the test effort, radiation hardened devices were being developed by International Rectifier and RCA/GE. The heavy-ion-induced burnout test results on available samples of these devices are also incorporated for comparison to the commercial and JEDEC versions tested.

  14. INDUCTION OF MAMMARY GLAND DEVELOPMENT IN ESTROGEN RECEPTOR-ALPHA KNOCKOUT MICE

    EPA Science Inventory

    Mammary glands from the estrogen receptor knockout ( ERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted Er signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute t...

  15. INDUCTION OF MAMMARY GLAND DEVELOPMENT IN ESTROGEN RECEPTOR-ALPHA KNOCKOUT MICE

    EPA Science Inventory

    Mammary glands from the estrogen receptor knockout ( ERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted Er signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute t...

  16. Heavy Rescue - Course Outline.

    DTIC Science & Technology

    1980-11-01

    used during heavy rescue operations . Methods and procedures for utilizing heavy rescue equipment. 4 Methods of developing improvised rescue equipment...utilizing available materials. A simulated exercise utilizing various rescue operations and techniques. Methods and procedures for the maintenance and...HEAVY RESCUE CONSIDERATIONS LEVEL I PERFORMANCE GOALS: 1 Hour GIVEN: 1. Summary of blocked access considerations during heavy rescue operations 2

  17. Regulation of Mammary Tumor Formation and Lipid Biosynthesis by Spot 14

    DTIC Science & Technology

    2013-10-01

    acts as a “master regulator” of mammary alveolar cell expansion during pregnancy and lactation2. In fact, mice lacking Elf5 in the mammary gland...diestrus-staged Neu and Neu/S14 females. The mammary gland is known to experience cycles of proliferation in response to the elevated progesterone ...predicts a role for S14 in breast cancer (Figure 12). In the normal mammary gland, S14 expression increases beginning in late pregnancy and is

  18. Targeted expression of activated Rac3 in mammary epithelium leads to defective postlactational involution and benign mammary gland lesions.

    PubMed

    Leung, Karen; Nagy, Andre; Gonzalez-Gomez, Ignacio; Groffen, John; Heisterkamp, Nora; Kaartinen, Vesa

    2003-01-01

    Rac3, a novel member of the Rho subfamily of the small GTPases, is frequently activated in cultured breast cancer cells and has been shown to mediate its effect via the p21-activated kinase (Pak) pathway. In order to evaluate these findings in vivo, we generated transgenic mice that express human constitutively active V12Rac under the control of the mouse mammary tumor virus (MMTV) promoter, which targets the transgene expression to the mammary epithelium. V12Rac3 expression could be detected during the first pregnancy, and the transgenic mammary gland tissues displayed an elevated Pak1 phosphorylation. Although milk proteins, beta-casein and whey acidic protein were expressed and milk fat globules accumulated normally during pregnancy, 60% of transgenic mothers failed to nurse their pups. Surprisingly, although full lactational differentiation was never achieved in transgenic mice, gland involution was incomplete. For 5 days after weaning, involution was normal, but thereafter, epithelial islands characteristic of this early stage of involution persisted for months. The apoptotic index decreased after 5 days, and these glands were associated with increased p38 MAPK phosphorylation. Nine months postpartum, the transgenic mammary glands still demonstrated a large amount of persistent epithelial islands and abnormally large ducts with lymphocyte infiltration, whereas the tissues of non-transgenic controls had returned to their normal 'virgin-like' phenotype. These data show that sustained activation of Rac3 in the mammary epithelium leads to impaired mammary gland physiology and results in the formation of mammary gland lesions. Copyright 2003 S. Karger AG, Basel

  19. Mammary analogue secretory carcinoma mimicking salivary adenoma.

    PubMed

    Williams, Lindsay; Chiosea, Simion I

    2013-12-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor characterized by ETV6 translocation. It appears that prior studies have identified MASC by reviewing salivary gland carcinomas, such as acinic cell carcinoma and adenocarcinoma, not otherwise specified. To address the possibility of MASC mimicking benign salivary neoplasms we reviewed 12 salivary gland (cyst)adenomas diagnosed prior to the discovery of MASC. One encapsulated (cyst)adenoma of the parotid gland demonstrated features of MASC. The diagnosis was confirmed by fluorescence in situ hybridization with an ETV6 break-apart probe. An unusual complex pattern of ETV6 rearrangement with duplication of the telomeric/distal ETV6 probe was identified. This case illustrates that MASC may mimic salivary (cyst)adenomas. To more accurately assess true clinical and morphologic spectrum of MASC, future studies may have to include review of salivary (cyst)adenomas. The differential diagnosis of MASC may have to be expanded to include cases resembling salivary (cyst)adenomas.

  20. Modeling mechanical interactions between cancerous mammary acini

    NASA Astrophysics Data System (ADS)

    Wang, Jeffrey; Liphardt, Jan; Rycroft, Chris

    2015-03-01

    The rules and mechanical forces governing cell motility and interactions with the extracellular matrix of a tissue are often critical for understanding the mechanisms by which breast cancer is able to spread through the breast tissue and eventually metastasize. Ex vivo experimentation has demonstrated the the formation of long collagen fibers through collagen gels between the cancerous mammary acini responsible for milk production, providing a fiber scaffolding along which cancer cells can disorganize. We present a minimal mechanical model that serves as a potential explanation for the formation of these collagen fibers and the resultant motion. Our working hypothesis is that cancerous cells induce this fiber formation by pulling on the gel and taking advantage of the specific mechanical properties of collagen. To model this system, we employ a new Eulerian, fixed grid simulation method to model the collagen as a nonlinear viscoelastic material subject to various forces coupled with a multi-agent model to describe individual cancer cells. We find that these phenomena can be explained two simple ideas: cells pull collagen radially inwards and move towards the tension gradient of the collagen gel, while being exposed to standard adhesive and collision forces.

  1. Breast cancer detection using mammary ductoscopy.

    PubMed

    Sauter, Edward

    2005-06-01

    Mammary ductoscopy (MD) has been used as a tool to evaluate the breast for cancer for over 10 years. MD allows the direct visualization of the duct lumen, providing a more targeted approach to the diagnosis of disease arising in the ductal system, since the lesion can be visualized and samples collected in the area of interest. Initial studies of MD evaluated women with pathologic spontaneous nipple discharge (PND), while more recent reports are also using MD to assess women without PND for the presence of breast cancer. Cytologic assessment of MD is highly specific but less sensitive in the detection of breast cancer. Nonetheless, a MD sample from a breast with PND may rarely undergo cytologic review and be interpreted as consistent with malignancy, only later to undergo surgical resection demonstrating benign pathology. For this reason, PND specimens interpreted as malignant on cytologic review require histopathologic confirmation prior to instituting therapy. Additional sample evaluation using image or molecular analysis may improve the sensitivity and specificity of MD in breast cancer detection.

  2. Heavy-ion radiotherapy

    NASA Astrophysics Data System (ADS)

    Kanai, Tatsuaki

    2000-11-01

    Heavy-ion radiotherapy using high-energy carbon beams has been performed at the National Institute of Radiological Sciences, Japan. The physical frame works for heavy-ion radiotherapy are established using physical understandings of radiation physics. In order to increase the accuracy of heavy-ion radiotherapy, many physical problems should be solved. Unsolved problems, such as the depth dose distributions, range of heavy-ion in patients and heavy-ion dosimetry in the radiation therapy, are discussed. .

  3. Involvement of Insulin Receptor Substrate 2 in Mammary Tumor Metastasis

    PubMed Central

    Nagle, Julie A.; Ma, Zhefu; Byrne, Maura A.; White, Morris F.; Shaw, Leslie M.

    2004-01-01

    The insulin receptor substrate (IRS) proteins are adaptor molecules that integrate signals generated by receptors that are implicated in human breast cancer. We investigated the specific contribution of IRS-2 to mammary tumor progression using transgenic mice that express the polyoma virus middle T antigen (PyV-MT) in the mammary gland and IRS-2-null (IRS-2−/−) mice. PyV-MT-induced tumor initiation and growth were similar in wild-type (WT) and IRS-2−/− mice. However, the latency and incidence of metastasis were significantly decreased in the absence of IRS-2 expression. The contribution of IRS-2 to metastasis is intrinsic to the tumor cells, because IRS-2−/− mammary tumor cells did not metastasize when grown orthotopically in the mammary fat pads of WT mice. WT and IRS-2−/− tumors contained similar numbers of mitotic cells, but IRS-2−/− tumors had a higher incidence of apoptosis than did WT tumors. In vitro, IRS-2−/− mammary tumor cells were less invasive and more apoptotic in response to growth factor deprivation than their WT counterparts. In contrast, IRS-1−/− tumor cells, which express only IRS-2, were highly invasive and were resistant to apoptotic stimuli. Collectively, our findings reveal an important contribution of IRS-2 to breast cancer metastasis. PMID:15509777

  4. Hormonal regulation of the immune microenvironment in the mammary gland.

    PubMed

    Need, Eleanor F; Atashgaran, Vahid; Ingman, Wendy V; Dasari, Pallave

    2014-07-01

    It is well established that the development and homeostasis of the mammary gland are highly dependent upon the actions of ovarian hormones progesterone and estrogen, as well as the availability of prolactin for the pregnant and lactating gland. More recently it has become apparent that immune system cells and cytokines play essential roles in both mammary gland development as well as breast cancer. Here, we review hormonal effects on mammary gland biology during puberty, menstrual cycling, pregnancy, lactation and involution, and dissect how hormonal control of the immune system may contribute to mammary development at each stage via cytokine secretion and recruitment of macrophages, eosinophils, mast cells and lymphocytes. Collectively, these alterations may create an immunotolerant or inflammatory immune environment at specific developmental stages or phases of the menstrual cycle. Of particular interest for further research is investigation of the combinatorial actions of progesterone and estrogen during the luteal phase of the menstrual cycle and key developmental points where the immune system may play an active role both in mammary development as well as in the creation of an immunotolerant environment, thereby affecting breast cancer risk.

  5. Windows in early mammary development: critical or not?

    PubMed

    Knight, C H; Sorensen, A

    2001-09-01

    Two critical windows in mammary development have been proposed. The first arises from observations in rodents that nutrition during fetal and neonatal periods can affect mammary ductular outgrowth, subsequent proliferative activity and, eventually, tumorigenesis, that is, potentially it could have a long-term effect on pathological outcome (breast cancer) in women. The second similarly involves early diet, but in this case the outcome is phenotypic, in that dairy heifers reared too quickly during the peripubertal period subsequently show impaired udder development and reduced milk yield persisting throughout life. Most mammary development occurs during pregnancy, but this period is usually thought of only in terms of the immediate outcome for the subsequent lactation; it is not believed to be a critical window, at least in terms of lifetime mammary productivity. This review examines the evidence underlying these various claims and attempts to define the mechanisms involved, and also considers whether derangements occurring earlier in life (prenatally) could also have long-term consequences for physiological or pathological mammary development.

  6. Classification and grading of canine malignant mammary tumors.

    PubMed

    Tavasoly, Abbas; Golshahi, Hannaneh; Rezaie, Annahita; Farhadi, Mohammad

    2013-01-01

    Histological grading is a good parameter to stratify tumors according to their biological aggressiveness. The Elston and Ellis grading method in humans, invasive ductal breast carcinomas and other invasive tumors are routinely used. The aims of this study were classification of mammary gland tumors and also application of a human grading method in canine mammary carcinoma. The samples included 37 tumors of mammary glands. Mammary tumors were carcinomas (n = 32) and sarcomas (n = 5). The carcinomas were classified as simple carcinoma 56.8% (n = 21), complex carcinoma 13.5% (n = 5), carcinoma arising from benign tumor 10.8% (n= 4) and special type of carcinoma 5.4% (n = 2). Out of 32 carcinomas studied, 37.5% (n = 12) grade I, 46.9% (n = 15) grade II and 15.6% (n = 5) grade III. This study demonstrated that the Elston and Ellis method of histological grading in canine mammary tumor is a reliable prognostic factor which is correlated with histopathological classification.

  7. In situ force mapping of mammary gland transformation.

    PubMed

    Lopez, Jose I; Kang, Inkyung; You, Weon-Kyoo; McDonald, Donald M; Weaver, Valerie M

    2011-09-01

    Tumor progression is characterized by an incremental stiffening of the tissue. The importance of tissue rigidity to cancer is appreciated, yet the contribution of specific tissue elements to tumor stiffening and their physiological significance remains unclear. We performed high-resolution atomic force microscopy indentation in live and snap-frozen fluorescently labeled mammary tissues to explore the origin of the tissue stiffening associated with mammary tumor development in PyMT mice. The tumor epithelium, the tumor-associated vasculature and the extracellular matrix all contributed to mammary gland stiffening as it transitioned from normal to invasive carcinoma. Consistent with the concept that extracellular matrix stiffness modifies cell tension, we found that isolated transformed mammary epithelial cells were intrinsically stiffer than their normal counterparts but that the malignant epithelium in situ was far stiffer than isolated breast tumor cells. Moreover, using an in situ vitrification approach, we determined that the extracellular matrix adjacent to the epithelium progressively stiffened as tissue evolved from normal through benign to an invasive state. Importantly, we also noted that there was significant mechanical heterogeneity within the transformed tissue both in the epithelium and the tumor-associated neovasculature. The vascular bed within the tumor core was substantially stiffer than the large patent vessels at the invasive front that are surrounded by the stiffest extracellular matrix. These findings clarify the contribution of individual mammary gland tissue elements to the altered biomechanical landscape of cancerous tissues and emphasize the importance of studying cancer cell evolution under conditions that preserve native interactions.

  8. Quantification of progesterone binding in mammary tissue of pregnant ewes

    SciTech Connect

    Smith, J.J.; Capuco, A.V.; Akers, R.M.

    1987-06-01

    Progestin-binding sites in mammary tissue from 14 prepartum, multiparous ewes at 50, 80, 115, and 140 d of gestation were demonstrated by the binding of (/sup 3/H) R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) to ovine mammary cytosol in the presence of sodium molybdate and excess cortisol. Homogenization extracted 89% of total mammary receptors (nuclear) into cytosol. Binding was specific for progestins and was of high affinity. The average dissociation constant for (/sup 3/H) R5020 specifically bound to receptors extracted into mammary cytosol was 1.9 (+/- .4) x 10/sup -9/ M (n = 14) and did not change significantly over the test period. However, binding capacities (fmol/mg cytosolic protein) differed according to stage of gestation with averages of 125 +/- 53, 149 +/- 26, 656 +/- 216, 57 +/- 22 at 50, 80, 115, and 140 d of pregnancy, respectively. Increased number of progestin-binding sites at 115 d of gestation (whether data are expressed per unit of tissue weight, DNA, or cytosolic protein) suggests that an increase per mammary epithelial cell may be necessary to produce the full lobuloalveolar proliferation observed at this stage of gestation.

  9. Isolation of Endoplasmic Reticulum Fractions from Mammary Epithelial Tissue.

    PubMed

    Chanat, Eric; Le Parc, Annabelle; Lahouassa, Hichem; Badaoui, Bouabid

    2016-06-01

    In the mammary glands of lactating animals, the mammary epithelial cells that surround the lumen of the acini produce and secrete copious amounts of milk. Functional differentiation of these mammary epithelial cells depends on the development of high-efficiency secretory pathways, notably for protein and lipid secretion. Protein secretion is a fundamental process common to all animal cells that involves a subset of cellular organelles, including the endoplasmic reticulum and the Golgi apparatus. In contrast, en masse secretion of triglycerides and cholesterol esters in the form of milk fat globules is a unique feature of the mammary epithelial cell. Cytoplasmic lipid droplets, the intracellular precursors of milk fat globules, originate from the endoplasmic reticulum, as do most milk-specific proteins. This organelle is therefore pivotal in the biogenesis of milk components. Fractionation of the cell into its subcellular parts is an approach that has proven very powerful for understanding organelle function and for studying the specific role of an organelle in a given cell activity. Here we describe a method for the purification of both smooth and rough microsomes, the membrane-bound endoplasmic reticulum fragments that form from endoplasmic reticulum domains when cells are broken up, from mammary gland tissue at lactation.

  10. Serotonin: a local regulator in the mammary gland epithelium.

    PubMed

    Horseman, Nelson D; Collier, Robert J

    2014-02-01

    Serotonin (5-hydroxytryptamine, 5-HT) is a very simple molecule that plays key roles in complex communication mechanisms within the animal body. In the mammary glands, serotonin biosynthesis and secretion are induced in response to dilation of the alveolar spaces. Since its discovery several years ago, mammary 5-HT has been demonstrated to perform two homeostatic functions. First, serotonin regulates lactation and initiates the transition into the earliest phases of involution. Second, serotonin is a local signal that induces parathyroid hormone-related peptide (PTHrP), which allows the mammary gland to drive the mobilization of calcium from the skeleton. These processes use different receptor types, 5-HT7 and 5-HT2, respectively. In this review, we provide synthetic perspectives on the fundamental processes of lactation homeostasis and the adaptation of calcium homeostasis for lactation. We analyze the role of the intrinsic serotonin system in the physiological regulation of the mammary glands. We also consider the importance of the mammary serotonin system in pathologies and therapies associated with lactation and breast cancer.

  11. Expression of novel, putative stem cell markers in prepubertal and lactating mammary glands of bovine

    USDA-ARS?s Scientific Manuscript database

    Mammary stem cells (MaSC) are essential for growth and maintenance of the mammary epithelium. Two main phases of mammary growth include ductal elongation prior to puberty and lobulo-alveolar growth and development during pregnancy. Some studies have utilized morphological characteristics and retenti...

  12. In vitro expansion of the mammary stem/progenitor cell population by xanthosinetreatment

    USDA-ARS?s Scientific Manuscript database

    Background: Mammary stem cells are critical for growth and maintenance of the mammary gland and therefore of considerable interest for improving productivity and efficiency of dairy animals. Xanthosine (Xs) treatment has been demonstrated to promote expansion of putative mammary stem cells in vivo ...

  13. Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate

    PubMed Central

    MacDougall, Lori D.

    2003-01-01

    A male, neutered cat was presented for lethargy, reluctance to walk, and mammary enlargement after recent treatment with megestrol acetate. Mammary fibroadenomatous hyperplasia was diagnosed on the basis of history, clinical signs, and histopathological findings. Pathogenesis, clinical signs, and treatment options for mammary fibroadenomatous hyperplasia attributed to megestrol acetate treatment are discussed. PMID:12677692

  14. Bovine mammary stem cells: Transcriptome profiling and the stem cell niche

    USDA-ARS?s Scientific Manuscript database

    Identification and transcriptome analysis of mammary stem cells (MaSC) are important steps toward understanding the molecular basis of mammary epithelial growth, homeostasis and tissue repair. Our objective was to evaluate the molecular profiles of four categories of cells within the bovine mammary ...

  15. Mammary carcinogenesis in rats: basic facts and recent results in Brookhaven

    SciTech Connect

    Shellabarger, C.J.; Stone, J.P.; Holtzman, s.

    1982-01-01

    Some research results from experiments investigating neutron-induced mammary carcinogenesis in rats are presented. The additive effects of neutrons and 3-methylcholanthrene on mammary adenocarcinoma were determined. Synergism between diethylstilbestrol and neutrons was likewise studied. Differences in mammary neoplastic response between strains of laboratory rats was also investigated. (ACR)

  16. Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma

    PubMed Central

    Nadolski, Amy C.; Markovich, Jessica E.; Jennings, Samuel H.; Mahony, Orla M.

    2016-01-01

    A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior. PMID:27708447

  17. Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma.

    PubMed

    Nadolski, Amy C; Markovich, Jessica E; Jennings, Samuel H; Mahony, Orla M

    2016-10-01

    A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior.

  18. The Analysis of Cell Population Dynamics in Mammary Gland Development and Tumorigenesis

    DTIC Science & Technology

    2006-08-01

    processes of mammary epithelial cell differentiation during developmentand tumorigenesis. Using FACS, mammary epithelial cell ( MEC ) populations from tumors...developed techniques for viral transduction andtransplantation of primary MECs . 15. SUBJECT TERMS mammary, stem cell, lentivirus, FACS, cancer, imaging 16...epithelial cell ( MEC ) populations from tumors and wildtype tissue was investigated for their outgrowth potential or tumorigenic capacity. We also developed

  19. Experimental elucidation of vacancy complexes associated with hydrogen ion-induced splitting of bulk GaN

    NASA Astrophysics Data System (ADS)

    Moutanabbir, O.; Scholz, R.; Gösele, U.; Guittoum, A.; Jungmann, M.; Butterling, M.; Krause-Rehberg, R.; Anwand, W.; Egger, W.; Sperr, P.

    2010-03-01

    We present a detailed study of the thermal evolution of H ion-induced vacancy related complexes and voids in bulk GaN implanted under ion-cut conditions. By using transmission electron microscopy, we found that the damage band in as-implanted GaN is decorated with a high density of nanobubbles of ˜1-2nm in diameter. Variable energy Doppler broadening spectroscopy showed that this band contains vacancy clusters and voids. In addition to vacancy clusters, the presence of VGa , VGa-H2 , and VGaVN complexes was evidenced by pulsed low-energy positron lifetime spectroscopy. Subtle changes upon annealing in these vacancy complexes were also investigated. As a general trend, a growth in open-volume defects is detected in parallel to an increase in both size and density of nanobubbles. The observed vacancy complexes appear to be stable during annealing. However, for temperatures above 450°C , unusually large lifetimes were measured. These lifetimes are attributed to the formation of positronium in GaN. Since the formation of positronium is not possible in a dense semiconductor, our finding demonstrates the presence of sufficiently large open-volume defects in this temperature range. Based on the Tao-Eldrup model, the average lattice opening during thermal annealing was quantified. We found that a void diameter of 0.4 nm is induced by annealing at 600°C . The role of these complexes in the subsurface microcracking is discussed.

  20. Effect of silver ion-induced disorder on morphological, chemical and optical properties of poly (methyl methacrylate)

    NASA Astrophysics Data System (ADS)

    Arif, Shafaq; Saleemi, Farhat; Rafique, M. Shahid; Naab, Fabian; Toader, Ovidiu; Mahmood, Arshad; Aziz, Uzma

    2016-11-01

    Ion implantation is a versatile technique to tailor the surface properties of polymers in a controlled manner. In the present study, samples of poly (methyl methacrylate) (PMMA) have been implanted with 400 keV silver (Ag+) ion beam to various ion fluences ranging from 5 × 1013 to 5 × 1015 ions/cm2. The effect of Ag+ ion-induced disorder on morphological, chemical and optical properties of PMMA is analyzed using Atomic Force Microscope (AFM), Fourier transform infrared spectroscopy (FTIR) and ultraviolet-visible (UV-Vis) spectroscopy. Furthermore, the electrical conductivity of pristine and implanted PMMA is measured using four probe apparatus. The AFM images revealed the growth of nano-sized grainy structures and hillocks above the surface of implanted PMMA. The FTIR spectra confirmed the modifications in chemical structure of PMMA along with the formation of sbnd Cdbnd Csbnd carbon contents. The refractive index, extinction coefficient and photoconductivity of implanted PMMA have been found to increase as a function of ion fluence. Simultaneously, indirect optical band gap is reduced from 3.13 to 0.81 eV at a relatively high fluence (5 × 1015 ions/cm2). A linear correlation has been established between the band gap and Urbach energies. Moreover, the electrical conductivity of Ag+ implanted PMMA has increased from 2.14 × 10-10 (pristine) to 9.6 × 10-6 S/cm.

  1. Low-energy ion induced Auger electron spectra and energy thresholds for some pure elements, compounds, and alloys

    SciTech Connect

    Fan, C.; Yu, Z.; Chen, X.

    1987-07-01

    By improvements of experimental method, ion induced Auger electron spectra (IAES) of pure elements, compounds, and alloys for 23 samples have been obtained successfully using a combined scanning Auger microscopy/secondary ion mass spectrometry instrument. Ar/sup +/ with energy up to 5 keV was the incident ion. The spectra measured are different from that obtained by electron-stimulated Auger, and correspondent Auger electron energies are not more than 500 eV. With increasing atomic number, the intensity of IAES peaks decreases. Some spectra of those samples and energy thresholds of all samples are given here. Many of them are not found yet in publications. The results showed that energy threshold values of elements go up with increasing atomic number and level off in the region of the fourth- and fifth-period elements. Among others, the thresholds of Mg, Al, and Si are 200, 350, and 600 eV, respectively, and much lower than the values reported before.

  2. White/blue-emitting, water-dispersible CdSe quantum dots prepared by counter ion-induced polymer collapse

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Goh, Jane Betty; Goh, M. Cynthia; Giri, Neeraj Kumar; Paige, Matthew F.

    2015-09-01

    The synthesis and characterization of water-dispersible, luminescent CdSe/ZnS semiconductor quantum dots that exhibit nominal "white" fluorescence emission and have potential applications in solid-state lighting is described. The nanomaterials, prepared through counter ion-induced collapse and UV cross-linking of high-molecular weight polyacrylic acid in the presence of appropriate aqueous inorganic ions, were of ∼2-3 nm diameter and could be prepared in gram quantities. The quantum dots exhibited strong luminescence emission in two bands, the first in the blue-region (band edge) of the optical spectrum and the second, a broad emission in the red-region (attributed to deep trap states) of the optical spectrum. Because of the relative strength of emission of the band edge and deep trap state luminescence, it was possible to achieve visible white luminescence from the quantum dots in aqueous solution and in dried, solid films. The optical spectroscopic properties of the nanomaterials, including ensemble and single-molecule spectroscopy, was performed, with results compared to other white-emitting quantum dot systems described previously in the literature.

  3. Possible Immune Regulation of Natural Killer T Cells in a Murine Model of Metal Ion-Induced Allergic Contact Dermatitis.

    PubMed

    Kumagai, Kenichi; Horikawa, Tatsuya; Shigematsu, Hiroaki; Matsubara, Ryota; Kitaura, Kazutaka; Eguchi, Takanori; Kobayashi, Hiroshi; Nakasone, Yasunari; Sato, Koichiro; Yamada, Hiroyuki; Suzuki, Satsuki; Hamada, Yoshiki; Suzuki, Ryuji

    2016-01-12

    Metal often causes delayed-type hypersensitivity reactions, which are possibly mediated by accumulating T cells in the inflamed skin, called irritant or allergic contact dermatitis. However, accumulating T cells during development of a metal allergy are poorly characterized because a suitable animal model is unavailable. We have previously established novel murine models of metal allergy and found accumulation of both metal-specific T cells and natural killer (NK) T cells in the inflamed skin. In our novel models of metal allergy, skin hypersensitivity responses were induced through repeated sensitizations by administration of metal chloride and lipopolysaccharide into the mouse groin followed by metal chloride challenge in the footpad. These models enabled us to investigate the precise mechanisms of the immune responses of metal allergy in the inflamed skin. In this review, we summarize the immune responses in several murine models of metal allergy and describe which antigen-specific responses occur in the inflamed skin during allergic contact dermatitis in terms of the T cell receptor. In addition, we consider the immune regulation of accumulated NK T cells in metal ion-induced allergic contact dermatitis.

  4. Int-6, a highly conserved, widely expressed gene, is mutated by mouse mammary tumor virus in mammary preneoplasia.

    PubMed Central

    Marchetti, A; Buttitta, F; Miyazaki, S; Gallahan, D; Smith, G H; Callahan, R

    1995-01-01

    With a unique mouse mammary tumor model system in which mouse mammary tumor virus (MMTV) insertional mutations can be detected during progression from preneoplasia to frank malignancy, including metastasis, we have discovered a new common integration site (designated Int-6) for MMTV in mouse mammary tumors. MMTV was integrated into Int-6 in a mammary hyperplastic outgrowth line, its tumors and metastases, and two independent mammary tumors arising in unrelated mice. The Int-6 gene is ubiquitously expressed as a 1.4-kb RNA species in adult tissues and is detected beginning at day 8 of embryonic development. The nucleotide sequence of Int-6 is unrelated to any of the known genes in the GenBank database. MMTV integrates within introns of the gene in the opposite transcriptional orientation. In each tumor tested, this results in the expression of a truncated Int-6/long terminal repeat (LTR) chimeric RNA species which is terminated at a cryptic termination signal in the MMTV LTR. Since the nonrearranged Int-6 alleles in these tumors contain no mutations, we favor the conclusion that truncation of the Int-6 gene product either biologically activates its function or represents a dominant-negative mutation. PMID:7853537

  5. Mammary Gland Reprogramming: Metalloproteinases Couple Form with Function

    PubMed Central

    Khokha, Rama; Werb, Zena

    2011-01-01

    The adult mammary structure provides for the rapid growth, development, and immunological protection of the live-born young of mammals through its production of milk. The dynamic remodeling of the branched epithelial structure of the mammary gland in response to physiological stimuli that allow its programmed branching morphogenesis at puberty, cyclical turnover during the reproductive cycle, differentiation into a secretory organ at parturition, postlactational involution, and ultimately, regression with age is critical for these processes. Extracellular metalloproteinases are essential for the remodeling programs that operate in the tissue microenvironment at the interface of the epithelium and the stroma, coupling form with function. Deregulated proteolytic activity drives the transition of a physiological mammary microenvironment into a tumor microenvironment, facilitating malignant transformation. PMID:21106646

  6. IGF Ligand and Receptor Regulation of Mammary Development

    PubMed Central

    Rowzee, Anne M.; Lazzarino, Deborah A.; Rota, Lauren; Sun, Zhaoyu; Wood, Teresa L.

    2009-01-01

    The insulin-like growth factors, IGF-I and IGF-II, have endocrine as well as autocrine-paracrine actions on tissue growth. Both IGF ligands are expressed within developing mammary tissue throughout postnatal stages with specific sites of expression in the epithelial and stromal compartments. The elucidation of circulating versus local actions and of epithelial versus stromal actions of IGFs in stimulating mammary epithelial development has been the focus of several laboratories. The recent studies addressing IGF ligand function provide support for the hypotheses that 1) the diverse sites of IGF expression may mediate different cellular outcomes, and 2) IGF-I and IGF-II are distinctly regulated and have diverse functions in mammary development. The mechanisms for IGF function likely are mediated, in part, through diverse IGF signaling receptors. The local actions of the IGF ligands and receptors as revealed through recent publications are the focus of this review. PMID:19020961

  7. TGF-beta biology in mammary development and breast cancer.

    PubMed

    Moses, Harold; Barcellos-Hoff, Mary Helen

    2011-01-01

    Transforming growth factor-β1 (TGF-β) was first implicated in mammary epithelial development by Daniel and Silberstein in 1987 and in breast cancer cells and hormone resistance by Lippman and colleagues in 1988. TGF-β is critically important for mammary morphogenesis and secretory function through specific regulation of epithelial proliferation, apoptosis, and extracellular matrix. Differential TGF-β effects on distinct cell types are compounded by regulation at multiple levels and the influence of context on cellular responses. Studies using controlled expression and conditional-deletion mouse models underscore the complexity of TGF-β biology across the cycle of mammary development and differentiation. Early loss of TGF-β growth regulation in breast cancer evolves into fundamental deregulation that mediates cell interactions and phenotypes driving invasive disease. Two outstanding issues are to understand the mechanisms of biological control in situ and the circumstances by which TGF-β regulation is subverted in neoplastic progression.

  8. Malignant mammary tumor in female dogs: environmental contaminants

    PubMed Central

    2010-01-01

    Mammary tumors of female dogs have greatly increased in recent years, thus demanding rapid diagnosis and effective treatment in order to determine the animal survival. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adjacent adipose tissue of canine mammary tumor. High Precision Liquid Chromatography - HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in nine female dogs, without predilection for breed or age. After surgery, masses were carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected to detect of environmental contaminants. The identified pyrethroids were allethrin, cyhalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 33.3%. Histopathology demonstrated six female dogs (66.7%) as having complex carcinoma and three (33.3%) with simple carcinoma. From these tumors, seven (77.8%) presented aggressiveness degree III and two (22.2%) degree I. Five tumors were positive for estrogen receptors in immunohistochemical analysis. The contamination level was observed in more aggressive tumors. This was the first report in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis. Hence, the dog may be used as a sentinel animal for human breast cancer, since human beings share the same environment and basically have the same eating habits. PMID:20587072

  9. Biology of glucose transport in the mammary gland.

    PubMed

    Zhao, Feng-Qi

    2014-03-01

    Glucose is the major precursor of lactose, which is synthesized in Golgi vesicles of mammary secretory alveolar epithelial cells during lactation. Glucose is taken up by mammary epithelial cells through a passive, facilitative process, which is driven by the downward glucose concentration gradient across the plasma membrane. This process is mediated by facilitative glucose transporters (GLUTs), of which there are 14 known isoforms. Mammary glands mainly express GLUT1 and GLUT8, and GLUT1 is the predominant isoform with a Km of ~10 mM and transport activity for mannose and galactose in addition to glucose. Mammary glucose transport activity increases dramatically from the virgin state to the lactation state, with a concomitant increase in GLUT expression. The increased GLUT expression during lactogenesis is not stimulated by the accepted lactogenic hormones. New evidence indicates that a possible low oxygen tension resulting from increased metabolic rate and oxygen consumption may play a major role in stimulating glucose uptake and GLUT1 expression in mammary epithelial cells during lactogenesis. In addition to its primary presence on the plasma membrane, GLUT1 is also expressed on the Golgi membrane of mammary epithelial cells and is likely involved in facilitating the uptake of glucose and galactose to the site of lactose synthesis. Because lactose synthesis dictates milk volume, regulation of GLUT expression and trafficking represents potentially fruitful areas for further research in dairy production. In addition, this research will have pathological implications for the treatment of breast cancer because glucose uptake and GLUT expression are up-regulated in breast cancer cells to accommodate the increased glucose need.

  10. Malignant mammary tumor in female dogs: environmental contaminants.

    PubMed

    Andrade, Fábio He; Figueiroa, Fernanda C; Bersano, Paulo Ro; Bissacot, Denise Z; Rocha, Noeme S

    2010-06-30

    Mammary tumors of female dogs have greatly increased in recent years, thus demanding rapid diagnosis and effective treatment in order to determine the animal survival. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adjacent adipose tissue of canine mammary tumor. High Precision Liquid Chromatography - HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in nine female dogs, without predilection for breed or age. After surgery, masses were carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected to detect of environmental contaminants. The identified pyrethroids were allethrin, cyhalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 33.3%. Histopathology demonstrated six female dogs (66.7%) as having complex carcinoma and three (33.3%) with simple carcinoma. From these tumors, seven (77.8%) presented aggressiveness degree III and two (22.2%) degree I. Five tumors were positive for estrogen receptors in immunohistochemical analysis. The contamination level was observed in more aggressive tumors. This was the first report in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis. Hence, the dog may be used as a sentinel animal for human breast cancer, since human beings share the same environment and basically have the same eating habits.

  11. Immunohistochemical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland

    NASA Technical Reports Server (NTRS)

    Ehrhart, E. J.; Gillette, E. L.; Barcellos-Hoff, M. H.; Chaterjee, A. (Principal Investigator)

    1996-01-01

    High-LET radiation has unique physical and biological properties compared to sparsely ionizing radiation. Recent studies demonstrate that sparsely ionizing radiation rapidly alters the pattern of extracellular matrix expression in several tissues, but little is known about the effect of heavy-ion radiation. This study investigates densely ionizing radiation-induced changes in extracellular matrix localization in the mammary glands of adult female BALB/c mice after whole-body irradiation with 0.8 Gy 600 MeV iron particles. The basement membrane and interstitial extracellular matrix proteins of the mammary gland stroma were mapped with respect to time postirradiation using immunofluorescence. Collagen III was induced in the adipose stroma within 1 day, continued to increase through day 9 and was resolved by day 14. Immunoreactive tenascin was induced in the epithelium by day 1, was evident at the epithelial-stromal interface by day 5-9 and persisted as a condensed layer beneath the basement membrane through day 14. These findings parallel similar changes induced by gamma irradiation but demonstrate different onset and chronicity. In contrast, the integrity of epithelial basement membrane, which was unaffected by sparsely ionizing radiation, was disrupted by iron-particle irradiation. Laminin immunoreactivity was mildly irregular at 1 h postirradiation and showed discontinuities and thickening from days 1 to 9. Continuity was restored by day 14. Thus high-LET radiation, like sparsely ionizing radiation, induces rapid-remodeling of the stromal extracellular matrix but also appears to alter the integrity of the epithelial basement membrane, which is an important regulator of epithelial cell proliferation and differentiation.

  12. Effects of alpha-particles on survival and chromosomal aberrations in human mammary epithelial cells

    NASA Technical Reports Server (NTRS)

    Durante, M.; Grossi, G. F.; Gialanella, G.; Pugliese, M.; Nappo, M.; Yang, T. C.

    1995-01-01

    We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of alpha-particles emitted from radon daughters, we concentrated our studies on the efficiency of alpha-particles. Confluent cultures of M/10 cells were exposed to accelerated alpha-particles [beam energy incident at the cell monolayer = 3.85 MeV, incident linear energy transfer (LET) in cell = 109 keV/microns] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for alpha-particles (D0 = 0.73 +/- 0.04 Gy), while a shoulder was observed for x-rays (alpha/beta = 2.9 Gy; D0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET alpha-particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for alpha-particles and linearquadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges.(ABSTRACT TRUNCATED AT 250 WORDS).

  13. Effects of alpha-particles on survival and chromosomal aberrations in human mammary epithelial cells

    NASA Technical Reports Server (NTRS)

    Durante, M.; Grossi, G. F.; Gialanella, G.; Pugliese, M.; Nappo, M.; Yang, T. C.

    1995-01-01

    We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of alpha-particles emitted from radon daughters, we concentrated our studies on the efficiency of alpha-particles. Confluent cultures of M/10 cells were exposed to accelerated alpha-particles [beam energy incident at the cell monolayer = 3.85 MeV, incident linear energy transfer (LET) in cell = 109 keV/microns] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for alpha-particles (D0 = 0.73 +/- 0.04 Gy), while a shoulder was observed for x-rays (alpha/beta = 2.9 Gy; D0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET alpha-particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for alpha-particles and linearquadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges.(ABSTRACT TRUNCATED AT 250 WORDS).

  14. Immunohistochemical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland

    SciTech Connect

    Ehrhart, E.J.; Gillette, E.L.; Barcellos-Hoff, M.H.

    1996-02-01

    High-LET radiation has unique physical and biological properties compared to sparsely ionizing radiation. Recent studies demonstrate that sparsely ionizing radiation rapidly alters the pattern of extracellular matrix expression in several tissues, but little is known about the effect of heavy-ion radiation. This study investigates densely ionizing radiation-induced changes in extracellular matrix localization in the mammary glands of adult female BALB/c mice after whole-body irradiation with 0.8 Gy 600 MeV iron particles. The basement membrane and interstitial extracellular matrix proteins of the mammary gland stroma were mapped with respect to time postirradiation using immunofluorescence. Collagen III was induced in the adipose stroma within 1 day, continued to increase through day 9 and was resolved by day 14. Immunoreactive tenascin was induced in the epithelium by day 1, was evident at the epithelial-stromal interface by day 5-9 and persisted as a condensed layer beneath the basement membrane through day 14. These findings parallel similar changes induced by {gamma} irradiation but demonstrate different onset and chronicity. In contrast, the integrity of epithelial basement membrane, which was unaffected by sparsely ionizing radiation, was disrupted by iron-particle irradiation. Laminin inummoreactivity was mildly irregular at 1 h postirradiation and showed discontinuities and thickening from days 1 to 9. Continuity was restored by day 14. Thus high-LET radiation, like sparsely ionizing radiation, induces rapid remodeling of the stromal extracellular matrix but also appears to alter the integrity of the epithelial basement membrane, which is an important regulator of epithelial cell proliferation and differentiation. 40 refs., 3 figs.

  15. Immunohistochemical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland

    NASA Technical Reports Server (NTRS)

    Ehrhart, E. J.; Gillette, E. L.; Barcellos-Hoff, M. H.; Chaterjee, A. (Principal Investigator)

    1996-01-01

    High-LET radiation has unique physical and biological properties compared to sparsely ionizing radiation. Recent studies demonstrate that sparsely ionizing radiation rapidly alters the pattern of extracellular matrix expression in several tissues, but little is known about the effect of heavy-ion radiation. This study investigates densely ionizing radiation-induced changes in extracellular matrix localization in the mammary glands of adult female BALB/c mice after whole-body irradiation with 0.8 Gy 600 MeV iron particles. The basement membrane and interstitial extracellular matrix proteins of the mammary gland stroma were mapped with respect to time postirradiation using immunofluorescence. Collagen III was induced in the adipose stroma within 1 day, continued to increase through day 9 and was resolved by day 14. Immunoreactive tenascin was induced in the epithelium by day 1, was evident at the epithelial-stromal interface by day 5-9 and persisted as a condensed layer beneath the basement membrane through day 14. These findings parallel similar changes induced by gamma irradiation but demonstrate different onset and chronicity. In contrast, the integrity of epithelial basement membrane, which was unaffected by sparsely ionizing radiation, was disrupted by iron-particle irradiation. Laminin immunoreactivity was mildly irregular at 1 h postirradiation and showed discontinuities and thickening from days 1 to 9. Continuity was restored by day 14. Thus high-LET radiation, like sparsely ionizing radiation, induces rapid-remodeling of the stromal extracellular matrix but also appears to alter the integrity of the epithelial basement membrane, which is an important regulator of epithelial cell proliferation and differentiation.

  16. MHC Class I-Related Antigen-Processing Machinery Component Defects in Feline Mammary Carcinoma1

    PubMed Central

    Favole, Alessandra; Cascio, Paolo; Cerruti, Fulvia; Sereno, Alessandra; Tursi, Massimiliano; Tomatis, Alessandro; Beffa, Cristina Della; Ferrone, Soldano; Bollo, Enrico

    2012-01-01

    Defects in HLA class I antigen-processing machinery (APM) component expression and/or function are frequent in human tumors. These defects may provide tumor cells with a mechanism to escape from recognition and destruction by HLA class I antigen-restricted, tumor antigen-specific cytotoxic T cells. However, expression and functional properties of MHC class I antigens and APM components in malignant cells in other animal species have been investigated to a limited extent. However, this information can contribute to our understanding of the mechanisms underlying the association of MHC class I antigen and APM component defects with malignant transformation of cells and to identify animal models to validate targeted therapies to correct these defects. To overcome this limitation in the present study, we have investigated the expression of the catalytic subunits of proteasome (Y, X, and Z) and of immunoproteasome (LMP2, LMP7, and LMP10) as well as of MHC class I heavy chain (HC) in 25 primary feline mammary carcinomas (FMCs) and in 23 matched healthy mammary tissues. We found a reduced expression of MHC class I HC and of LMP2 and LMP7 in tumors compared with normal tissues. Concordantly, proteasomal cleavage specificities in extracts from FMCs were different from those in healthy tissues. In addition, correlation analysis showed that LMP2 and LMP7 were concordantly expressed in FMCs, and their expression was significantly correlated with that of MHC class I HC. The abnormalities we have found in the APM in FMCs may cause a defective processing of some tumor antigens. PMID:22348176

  17. Polyurethane-covered mammary implants: a 12-year experience.

    PubMed

    Gasperoni, C; Salgarello, M; Gargani, G

    1992-10-01

    Polyurethane-covered mammary implants are the implants of choice in aesthetic and reconstructive mammary surgery. These implants give very good results in regard to breast contour and consistency, and have a very low complication rate. We present our 12-year experience using polyurethane-covered prostheses. We place the implant mostly in the subglandular or subcutaneous site, and their capsular contracture rate is extremely low (3.3%). Based on our experience, we also review the other complications and side effects occurring with polyurethane prostheses and discuss them in detail.

  18. The contribution of growth hormone to mammary neoplasia

    PubMed Central

    Perry, Jo K; Mohankumar, Kumarasamypet M; Emerald, B Starling; Mertani, Hichem C; Lobie, Peter E

    2008-01-01

    While the effects of growth hormone (GH) on longitudinal growth are well established, the observation that GH contributes to neoplastic progression is more recent. Accumulating literature implicates GH-mediated signal transduction in the development and progression of a wide range malignancies including breast cancer. Recently autocrine human GH been demonstrated to be an orthotopically expressed oncogene for the human mammary gland. This review will highlight recent evidence linking GH and mammary carcinoma and discuss GH-antagonism as a potential therapeutic approach for treatment of breast cancer. PMID:18253708

  19. Radiogenic neoplasia in thyroid and mammary clonogens

    SciTech Connect

    Clifton, K.H.

    1992-05-20

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process.

  20. Mammary gland development: cell fate specification, stem cells and the microenvironment.

    PubMed

    Inman, Jamie L; Robertson, Claire; Mott, Joni D; Bissell, Mina J

    2015-03-15

    The development of the mammary gland is unique: the final stages of development occur postnatally at puberty under the influence of hormonal cues. Furthermore, during the life of the female, the mammary gland can undergo many rounds of expansion and proliferation. The mammary gland thus provides an excellent model for studying the 'stem/progenitor' cells that allow this repeated expansion and renewal. In this Review, we provide an overview of the different cell types that constitute the mammary gland, and discuss how these cell types arise and differentiate. As cellular differentiation cannot occur without proper signals, we also describe how the tissue microenvironment influences mammary gland development.

  1. A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis

    PubMed Central

    Chen, Qian; Zhang, Nailing; Gray, Ryan S.; Li, Huili; Ewald, Andrew J.; Zahnow, Cynthia A.; Pan, Duojia

    2014-01-01

    Despite recent progress, the physiological role of Hippo signaling in mammary gland development and tumorigenesis remains poorly understood. Here we show that the Hippo pathway is functionally dispensable in virgin mammary glands but specifically required during pregnancy. In contrast to many other tissues, hyperactivation of YAP in mammary epithelia does not induce hyperplasia but leads to defects in terminal differentiation. Interestingly, loss of YAP causes no obvious defects in virgin mammary glands but potently suppresses oncogene-induced mammary tumors. The selective requirement for YAP in oncogenic growth highlights the potential of YAP inhibitors as molecular targeted therapies against breast cancers. PMID:24589775

  2. The mammary glands of the Amazonian manatee, Trichechus inunguis (Mammalia: Sirenia): morphological characteristics and microscopic anatomy.

    PubMed

    Rodrigues, Fernanda Rosa; da Silva, Vera Maria Ferreira; Barcellos, José Fernando Marques

    2014-08-01

    The mammaries from carcasses of two female Amazonian manatees were examined. Trichechus inunguis possesses two axillary mammaries beneath the pectoral fins, one on each side of the body. Each papilla mammae has a small hole on its apex--the ostium papillare. The mammaries are covered by a stratified squamous keratinized epithelium. The epithelium of the mammary ducts became thinner more deeply in the tissue and varied from stratified to simple cuboidal. There was no evidence of glandular activity or secretion into the ducts of the mammary glands.

  3. Activation of p21(CIP1/WAF1) in mammary epithelium accelerates mammary tumorigenesis and promotes lung metastasis.

    PubMed

    Cheng, Xiaoyun; Xia, Weiya; Yang, Jer-Yen; Hsu, Jennifer L; Chou, Chao-Kai; Sun, Hui-Lung; Wyszomierski, Shannon L; Mills, Gordon B; Muller, William J; Yu, Dihua; Hung, Mien-Chie

    2010-12-03

    While p21 is well known to inhibit cyclin-CDK activity in the nucleus and it has also been demonstrated to have oncogenic properties in different types of human cancers. In vitro studies showed that the oncogenic function of p21is closely related to its cytoplasmic localization. However, it is unclear whether cytoplasmic p21 contributes to tumorigenesis in vivo. To address this question, we generated transgenic mice expressing the Akt-phosphorylated form of p21 (p21T145D) in the mammary epithelium. The results showed that Akt-activated p21 was expressed in the cytoplasm of mammary epithelium. Overexpression of Akt-activated p21 accelerated tumor onset and promoted lung metastasis in MMTV/neu mice, providing evidence that p21, especially cytoplasmic phosphorylated p21, has an oncogenic role in promoting mammary tumorigenesis and metastasis.

  4. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats

    PubMed Central

    Kakehashi, Anna; Yoshida, Midori; Tago, Yoshiyuki; Ishii, Naomi; Okuno, Takahiro; Gi, Min; Wanibuchi, Hideki

    2016-01-01

    Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3%, and more pronouncedly, at 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA. PMID:27827907

  5. Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors.

    PubMed

    Raposo-Ferreira, T M M; Bueno, R C; Terra, E M; Avante, M L; Tinucci-Costa, M; Carvalho, M; Cassali, G D; Linde, S D; Rogatto, S R; Laufer-Amorim, R

    2016-11-01

    The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively, in normal mammary gland samples (n = 10), benign mammary tumors (n = 11), nonmetastatic mammary carcinomas (n = 19), and metastatic mammary carcinomas (n = 11). Lower ATM transcript levels were detected in benign mammary tumors and carcinomas compared with normal mammary glands (P = .011). Similarly, lower ATM protein expression was observed in benign tumors (P = .0003), nonmetastatic mammary carcinomas (P < .0001), and the primary sites of metastatic carcinomas (P < .0001) compared with normal mammary glands. No significant differences in ATM gene or protein levels were detected among benign tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein downregulation is involved in canine mammary gland tumorigenesis. © The Author(s) 2016.

  6. HORMONAL INFLUENCES ON MAMMARY TUMORS OF THE RAT

    PubMed Central

    Huggins, Charles; Torralba, Yolanda; Mainzer, Klaus

    1956-01-01

    A transplanted mammary fibroadenoma was found to grow in 95 per cent of intact adult female rats and the increment of tumor weights was progressive and logarithmic. The growth of the tumor was retarded by ovariectomy and still more when this was combined with adrenalectomy. In ovariectomized rats the growth of the tumor was stimulated by phenolic estrogens, this increase being enhanced when progesterone was added. In these responses to hormonal changes the mammary gland and the tumor resembled each other. Yet there are many differences between the growth of the fibroadenoma and that of the mammary gland. In contrast to the progressive growth which occurred in intact adult females there was a prolonged period of indolent growth of transplants in hypophysectomized rats; but after many weeks active growth began and the tumors eventually reached large size. During the period of quiescent growth the tumor was cytologically atrophic but after the growth spurt had started the microscopic appearance of the fibroadenoma resembled that of tumors growing in normal adult females. The mammary gland remained atrophic during both the slow and the accelerated phases of tumor growth, and so too with the other secondary sex expressions. In hypophysectomized rats estrone and progesterone, when combined, stimulated the growth of the tumor, and this growth was accelerated by the additional administration of lactogenic or growth hormones. None of these hormones, separately, stimulated the growth of the tumor. In ovariectomized rats other differences were demonstrated between the growth of the mammary gland and the fibroadenoma. Progesterone, injected alone, accelerated the growth of the tumor but not that of the mammary glands. The administration of phenolic estrogens exerted a biphasic effect on the growth of the tumor whilst that on the breast of its hosts was monophasic. With progressively increasing doses of these phenols there occurred primarily an augmentation of the rate of

  7. The male mammary gland: a target for the xenoestrogen bisphenol A.

    PubMed

    Vandenberg, Laura N; Schaeberle, Cheryl M; Rubin, Beverly S; Sonnenschein, Carlos; Soto, Ana M

    2013-06-01

    Males of some strains of mice retain their mammary epithelium even in the absence of nipples. Here, we have characterized the mammary gland in male CD-1 mice both in whole mounts and histological sections. We also examined the effects of bisphenol A (BPA), an estrogen mimic that alters development of the female mouse mammary gland. BPA was administered at a range of environmentally relevant doses (0.25-250μg/kg/day) to pregnant and lactating mice and then the mammary glands of male offspring were examined at several periods in adulthood. We observed age- and dose-specific effects on mammary gland morphology, indicating that perinatal BPA exposures alter the male mammary gland in adulthood. These results may provide insight into gynecomastia, the most common male breast disease in humans, where proliferation of the mammary epithelium leads to breast enlargement.

  8. Quantification of mammary organoid toxicant response and mammary tissue motility using OCT fluctuation spectroscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Yu, Xiao; Blackmon, Richard L.; Carabas-Hernendez, Patricia; Fuller, Ashley; Troester, Melissa A.; Oldenburg, Amy L.

    2016-03-01

    Mammary epithelial cell (MEC) organoids in 3D culture recapitulate features of breast ducts in vivo. OCT has the ability to monitor the evolution of MEC organoids non-invasively and longitudinally. The anti-cancer drug Doxorubicin (Dox) is able to inhibit proliferation of cancer cells and has been widely used for chemotherapy of breast cancers; while environmental toxins implicated in breast cancer such as estrogen regulates mammary tumor growth and stimulates the proliferation and metastatic potential of breast cancers. Here we propose a quantitative method for measuring motility of breast cells in 3D cultures based upon OCT speckle fluctuation spectroscopy. The metrics of the inverse power-law exponent (α) and fractional modulation amplitude (M) were extracted from speckle fluctuation spectra. These were used to quantify the responses of MEC organoids to Dox, and estrogen. We investigated MEC organoids comprised of two different MEC lines: MCF10DCIS.com exposed to Dox, and MCF7 exposed to estrogen. We found an increase (p<0.001) in α of MEC along time (t=0, 1 hour, 24 hours, 48 hours and 6 days) at each dose of Dox (0, 1 μM and 10 μM), indicating lower fluctuation intensity at higher frequencies. We also observed a decrease (p<0.001) in M for increasing time. However, both α and M of MCF7 treated with estrogen (0, 1 nM and 10 nM) exhibited the opposite trend along time. This novel technology provides rapid and non-invasive measurements of the effects of toxicants on MEC motility for understanding breast cancer development and assessing anti-cancer drugs.

  9. Experimental elucidation of vacancy complexes associated with hydrogen ion-induced splitting of bulk GaN

    SciTech Connect

    Moutanabbir, O.; Scholz, R.; Goesele, U.; Guittoum, A.; Jungmann, M.; Butterling, M.; Krause-Rehberg, R.; Anwand, W.; Egger, W.; Sperr, P.

    2010-03-15

    We present a detailed study of the thermal evolution of H ion-induced vacancy related complexes and voids in bulk GaN implanted under ion-cut conditions. By using transmission electron microscopy, we found that the damage band in as-implanted GaN is decorated with a high density of nanobubbles of approx1-2 nm in diameter. Variable energy Doppler broadening spectroscopy showed that this band contains vacancy clusters and voids. In addition to vacancy clusters, the presence of V{sub Ga}, V{sub Ga}-H{sub 2}, and V{sub Ga}V{sub N} complexes was evidenced by pulsed low-energy positron lifetime spectroscopy. Subtle changes upon annealing in these vacancy complexes were also investigated. As a general trend, a growth in open-volume defects is detected in parallel to an increase in both size and density of nanobubbles. The observed vacancy complexes appear to be stable during annealing. However, for temperatures above 450 deg. C, unusually large lifetimes were measured. These lifetimes are attributed to the formation of positronium in GaN. Since the formation of positronium is not possible in a dense semiconductor, our finding demonstrates the presence of sufficiently large open-volume defects in this temperature range. Based on the Tao-Eldrup model, the average lattice opening during thermal annealing was quantified. We found that a void diameter of 0.4 nm is induced by annealing at 600 deg. C. The role of these complexes in the subsurface microcracking is discussed.

  10. Intermediate energy heavy ion reactions

    NASA Astrophysics Data System (ADS)

    Grégoire, C.; Tamain, B.

    The intermediate energy heavy ion induced reactions are extensively studied for several years. In this paper, we try to summarize the present knowledge. The peripheral reactions appear to be intermediate between the fragmentation and the deep inelastic regimes. Many questions remain open concerning the energy relaxation mechanisms and an eventual participant zone creation. In the case of central collisions, it has been shown that very hot nuclei can be built. The fusion limits are discussed and the very hot nuclei properties are considered. In some cases, hot spot formation or compression effects could play a role. Multifragmentation is discussed as a possible decay channel. In all these aspects, a difficult question concerns the validity of the temperature concept and more generally of collective thermodynamical variables. Such collective effects have been investigated in pion production experiments. Les réactions induites par ions lourds d'énergie intermédiaire sont très étudiées depuis quelques années. Dans cet article, nous essayons de résumer l'état actuel des connaissances. Les mécanismes mis en jeu dans les collisions périphériques sont intermédiaires entre les collisions très inélastiques et la fragmentation. La cible joue clairement un rôle déterminant et des effets importants de champ moyen demeurent. De nombreuses questions restent sans réponse comme par exemple les mécanismes de relaxation d'énergie ou l'existence d'une éventuelle zone participante. Dans le cas des collisions centrales, il a pu être montré que des noyaux très chauds sont fabriqués. Les limites au processus de fusion et les propriétés des noyaux très chauds sont discutées. Dans certains cas, des effets de compression ou de points chauds peuvent être envisagés. La multifragmentation est une voie de désexcitation possible. Une importante question concerne la validité du concept de température et plus généralement la notion de variable collective

  11. Laminin mediates tissue-specific gene expression in mammary epithelia

    PubMed Central

    1995-01-01

    Tissue-specific gene expression in mammary epithelium is dependent on the extracellular matrix as well as hormones. There is good evidence that the basement membrane provides signals for regulating beta-casein expression, and that integrins are involved in this process. Here, we demonstrate that in the presence of lactogenic hormones, laminin can direct expression of the beta-casein gene. Mouse mammary epithelial cells plated on gels of native laminin or laminin-entactin undergo functional differentiation. On tissue culture plastic, mammary cells respond to soluble basement membrane or purified laminin, but not other extracellular matrix components, by synthesizing beta-casein. In mammary cells transfected with chloramphenicol acetyl transferase reporter constructs, laminin activates transcription from the beta- casein promoter through a specific enhancer element. The inductive effect of laminin on casein expression was specifically blocked by the E3 fragment of the carboxy terminal region of the alpha 1 chain of laminin, by antisera raised against the E3 fragment, and by a peptide corresponding to a sequence within this region. Our results demonstrate that laminin can direct tissue-specific gene expression in epithelial cells through its globular domain. PMID:7730398

  12. Mapping Mammary Carcinoma Suppressor Genes in the Laboratory Rat

    DTIC Science & Technology

    1997-07-01

    AD GRANT NUMBER DAMDI7-94-J-4040 TITLE: Mapping Mammary Carcinoma Suppressor Genes in the Laboratory Rat PRINCIPAL INVESTIGATOR: Michael Gould, Ph.D...Carcinoma Suppressor Genes in the Laboratory Rat DAMDI7-94-J-4040 6. AUTHOR(S) Michael Gould, Ph.D. Hong Lan, Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND

  13. Aflatoxins ingestion and canine mammary tumors: There is an association?

    PubMed

    Frehse, M S; Martins, M I M; Ono, E Y S; Bracarense, A P F R L; Bissoqui, L Y; Teixeira, E M K; Santos, N J R; Freire, R L

    2015-10-01

    The aim of this study was to determine the presence of mycotoxins on dogs feed and to explore the potential association between mycotoxins exposure and the chance of mamary tumors in a case-control study. The study included 256 female dogs from a hospital population, 85 with mammary tumors (case group) and 171 without mammary tumors (control group). An epidemiological questionnaire was applied to both groups, and the data were analyzed by the EpiInfo statistical package. For the study, 168 samples of the feed offered to dogs were analyzed for the presence of aflatoxins, fumonisins and zearalenone by high-performance liquid chromatography. Mycotoxins were found in 79 samples (100%) in the case group and 87/89 (97.8%) in the control group. Mycotoxins were detected in all types of feed, regardless feed quality. Level of aflatoxin B1 (p = 0.0356, OR = 2.74, 95%, CI 1.13 to 6.60), aflatoxin G1 (AFG1) (p = 0.00007, OR = 4.60, 95%, CI = 2.16 to 9.79), and aflatoxin G2 (AFG2) (p = 0.0133, OR = 9.91, 95%, CI 1.21 to 81.15) were statistically higher in case of mammary cancer. In contrast, neutering was a protective factor for mammary cancer (p = 0.0004, OR = 0.32, 95%, CI = 0.17 to 0.60).

  14. MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

    EPA Science Inventory

    Mammary Gland Development: Early Life Effects from the Environment

    S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

    As signs of precocious puberty in girls reach ...

  15. MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

    EPA Science Inventory

    Mammary Gland Development: Early Life Effects from the Environment

    S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

    As signs of precocious puberty in girls reach ...

  16. The role of activin in mammary gland development and oncogenesis.

    PubMed

    Dunphy, Karen A; Schneyer, Alan L; Hagen, Mary J; Jerry, D Joseph

    2011-06-01

    TGFβ contributes to mammary gland development and has paradoxical roles in breast cancer because it has both tumor suppressor and tumor promoter activity. Another member of the TGFβ superfamily, activin, also has roles in the developing mammary gland, but these functions, and the role of activin in breast cancer, are not well characterized. TGFβ and activin share the same intracellular signaling pathways, but divergence in their signaling pathways are suggested. The purpose of this review is to compare the spatial and temporal expression of TGFβ and activin during mammary gland development, with consideration given to their functions during each developmental period. We also review the contributions of TGFβ and activin to breast cancer resistance and susceptibility. Finally, we consider the systemic contributions of activin in regulating obesity and diabetes; and the impact this regulation has on breast cancer. Elevated levels of activin in serum during pregnancy and its influence on pregnancy associated breast cancer are also considered. We conclude that evidence demonstrates that activin has tumor suppressing potential, without definitive indication of tumor promoting activity in the mammary gland, making it a good target for development of therapeutics.

  17. Amphiregulin: role in mammary gland development and breast cancer.

    PubMed

    McBryan, Jean; Howlin, Jillian; Napoletano, Silvia; Martin, Finian

    2008-06-01

    Extensive epithelial cell proliferation underlies the ductal morphogenesis of puberty that generates the mammary tree that will eventually fill the fat pad. This estrogen-dependent process is believed to be essentially dependent on locally produced growth factors that act in a paracrine fashion. EGF-like growth factor ligands, acting through EGF receptors are some of the principal promoters of pubertal ductal morphogenesis. Amphiregulin is the most abundant EGF-like growth factor in the pubertal mammary gland. Its gene is transcriptionally regulated by ERalpha, and recent evidence identifies it as a key mediator of the estrogen-driven epithelial cell proliferation of puberty: The pubertal deficiency in mammary gland ductal morphogenesis in ERalpha, amphiregulin, and EGFR knockout mice phenocopy each other. As a prognostic indicator in human breast cancer, amphiregulin indicates an outcome identical to that predicted by ERalpha presence. Despite this, a range of studies both on preneoplastic human breast tissue and on cell culture based models of breast cancer, suggest a possibly significant role for amphiregulin in driving human breast cancer progression. Here we summarise our current understanding of amphiregulin's contribution to mammary gland development and breast cancer progression.

  18. [Controversy about internal mammary chain irradiation in breast cancer].

    PubMed

    Hennequin, C; Fourquet, A

    2014-10-01

    Irradiation of lymph nodes areas after surgery of breast cancer, and specifically of the internal mammary chain, is an open question, frequently discussed. Three randomised trials (French, European-EORTC, Canadian) have been recently published or presented. The French trial did not show any benefit for internal mammary chain irradiation, but it was probably underpowered. The EORTC and Canadian trials demonstrated an improvement in overall survival after lymph nodes irradiation, including the internal mammary chain. The absolute benefit is 1.6% (hazard ratio-0.88 in a recent meta-analysis). Because this benefit is limited, it is important to define the characteristics of the patients who may benefit from this irradiation. Analyses of the randomized trials are not complete, and it is difficult at this moment to accurately define this population. However, cardiac and pulmonary toxicity of lymph nodes irradiation is well known. For each patient, evaluation of the potential late toxicity must be evaluated and so an accurate dosimetry for critical organs must be performed: the indication of internal mammary chain irradiation depends of the benefit/risk ratio. Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  19. Mammary carcinoma developing after radiotherapy and chemotherapy for Hodgkin's disease

    SciTech Connect

    Janjan, N.A.; Wilson, J.F.; Gillin, M.; Anderson, T.; Greenberg, M.; Schewe, K.; Cox, J.D.

    1988-01-15

    Two patients developed breast cancer after treatment of Hodgkin's disease. Both had received mediastinal irradiation 13 to 15 years, respectively, before the diagnosis of breast carcinoma. One patient had synchronous bilateral breast cancer when the diagnosis was made. Discussed is the risk of mammary carcinoma as a second malignant neoplasm in patients treated for Hodgkin's disease.

  20. Laminin Mediates Tissue-specific Gene Expression in Mammary Epithelia

    SciTech Connect

    Streuli, Charles H; Schmidhauser, Christian; Bailey, Nina; Yurchenco, Peter; Skubitz, Amy P. N.; Roskelley, Calvin; Bissell, Mina J

    1995-04-01

    Tissue-specific gene expression in mammary epithelium is dependent on the extracellular matrix as well as hormones. There is good evidence that the basement membrane provides signals for regulating beta-casein expression, and that integrins are involved in this process. Here, we demonstrate that in the presence of lactogenic hormones, laminin can direct expression of the beta-casein gene. Mouse mammary epithelial cells plated on gels of native laminin or laminin-entactin undergo functional differentiation. On tissue culture plastic, mammary cells respond to soluble basement membrane or purified laminin, but not other extracellular matrix components, by synthesizing beta-casein. In mammary cells transfected with chloramphenicol acetyl transferase reporter constructs, laminin activates transcription from the beta-casein promoter through a specific enhancer element. The inductive effect of laminin on casein expression was specifically blocked by the E3 fragment of the carboxy terminal region of the alpha 1 chain of laminin, by antisera raised against the E3 fragment, and by a peptide corresponding to a sequence within this region. Our results demonstrate that laminin can direct tissue-specific gene expression in epithelial cells through its globular domain.

  1. FEEDING GENISTEIN TO PREPUBERTAL GILTS STIMULATES THEIR MAMMARY DEVELOPMENT

    USDA-ARS?s Scientific Manuscript database

    The possible role of dietary genistein on mammary development of prepubertal gilts was investigated. Forty-five gilts were fed one of three diets from 90 d of age until slaughter (day 183 ± 1). Diets were: without soya (CTL0, n=15); soya-based commercial (CTLS, n=15); and soya-based commercial with ...

  2. Undergraduate Training in Mammary Gland Biology and Breast Cancer

    DTIC Science & Technology

    2005-05-01

    the Office of Management and Budget, Paperwork Reduction Proiect (0704-0188), Washington, DC 20503 1. AGENCY USE ONLY 2. REPORT DATE 3 . REPORT TYPE AND... 3 Introduction .................................................................................... 5 Body...receptors that mediate cell-cell interactions ( 3 ). Studies have shown that when unirradiated non-tumorigenic mammary epithelial COMMA-D cells were

  3. The Cellular Targets of Estrogen in Mammary Ductal Development

    DTIC Science & Technology

    2000-06-01

    DAMD17-99-1-9109 Organization: University of California, San Francisco Those portions of the technical data contained in this report marked as limited...Src tyrosine kinase is required for the induction of mammary tumors in transgenic mice. Genes Dev, 8,23-32 Li, B., Rosen, J. M., McMenamin , B. J

  4. Cholera toxin stimulation of human mammary epithelial cells in culture

    SciTech Connect

    Stampfer, M.R.

    1982-06-01

    Addition of cholera toxin to human mammary epithelial cultures derived from reduction mammoplasties and primary carcinomas greatly stimulated cell growth and increased the number of times the cells could be successfully subcultured. Other agents known to increase intracellular cAMP levels were also growth stimulatory. The increased growth potential conferred by cholera toxin enhances the usefulness of this cell culture system.

  5. The epigenetic landscape of mammary gland development and functional differentiation

    USDA-ARS?s Scientific Manuscript database

    Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conf...

  6. Cooperative Interactions During Human Mammary Epithelial Cell Immortalization

    DTIC Science & Technology

    2005-07-01

    Immortal Transformation of Cultured Human Mammary Epithelial Cells. Cellular Oncology, 26:248-251, 2004. Rodier , F., Kim, S-H., Nijjar, T., Yaswen, P...Promoter, Mol. Cell Biol.: 25:3923-3933, 2005. Goldstein, J, Rodier , F, Garbe, J, Stampfer, M, Campisi, J, Caspase-independent cytochrome c release is a

  7. Precursors of hexoneogenesis within the human mammary gland

    USDA-ARS?s Scientific Manuscript database

    The human mammary gland is capable of de novo synthesis of glucose and galactose (hexoneogenesis); however, the carbon source is incompletely understood. In this study, we investigated the role of acetate, glutamine, lactate and glycerol as potential carbon sources for hexoneogenesis. Healthy breast...

  8. Notch3 marks clonogenic mammary luminal progenitor cells in vivo

    PubMed Central

    Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis

    2013-01-01

    The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive “triple negative” human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2SAT transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells. PMID:24100291

  9. Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

    PubMed

    Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis; Fre, Silvia

    2013-10-14

    The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

  10. Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

    PubMed Central

    Jayasri, K.; Padmaja, K.; Saibaba, M.

    2016-01-01

    Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS), glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD) were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175%) was found to be increased, whereas glucose-6-phosphatase (33%), fructose-1, 6-bisphosphatase (42%), and G6PD (5 fold) activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors. PMID:28096627

  11. Gene Regulation by Retinoid Receptors in Human Mammary Epithelial Cells

    DTIC Science & Technology

    2002-10-01

    Hamann , P. Jenti, B. Imhof, and D. Vestweber. 1993. A death and tissue remodeling during mouse mammary gland involution. De- monoclonal antibody...Cell Growth Differ 10:49-59. Kato J-Y, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ . 1993. Snowden AW, Perkins ND. 1998. Cell cycle regulation of the

  12. Occurrence of mammary tumors in beagls given radium-226

    SciTech Connect

    Bruenger, F.W.; Lloyd, R.D.; Miller, S.C.; Taylor, G.N.; Angus, W.; Huth, D.A.

    1994-06-01

    A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with {sup 226}Ra at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 156 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs and 59 of 61 dogs given {sup 226}Ra survived the minimum age for diagnosis of mammary tumors of 3.75 years. Based on the observed age-dependent tumor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in the radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indicated no increased risk for the first tumor occurrence in irradiated dogs. Cox regression analysis of the multivariate risk sets showed no significantly increased risk for the occurrence of benign tumors but a statistically higher risk of 1.66 with a confidence interval of 1.15-2.40 for the occurrence of malignant tumors. The increased risk was dependent on dose, but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized dogs at time of surgery decreased the relative risks slightly but did not alter the significance. Exposure to diagnostic X rays with cumulative exposures below 0.2 Gy had no effect on tumor formation. It is unknown whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irradiation of fatty mammary tissue from transient radon {yields} polonium deposition, or a general effect of the overall radium deposition on the immune system of the dogs that lowered their resistance to formation of mammary tumors. 27 refs., 5 figs., 4 tabs.

  13. Three-Dimensional Cultures of Mouse Mammary Epithelial Cells

    PubMed Central

    Mroue, Rana; Bissell, Mina J.

    2013-01-01

    The mammary gland is an ideal “model organism” for studying tissue specificity and gene expression in mammals: it is one of the few organs that develop after birth and it undergoes multiple cycles of growth, differentiation and regression during the animal’s lifetime in preparation for the important function of lactation. The basic “functional differentiation” unit in the gland is the mammary acinus made up of a layer of polarized epithelial cells specialized for milk production surrounded by myoepithelial contractile cells, and the two-layered structure is surrounded by basement membrane. Much knowledge about the regulation of mammary gland development has been acquired from studying the physiology of the gland and of lactation in rodents. Culture studies, however, were hampered by the inability to maintain functional differentiation on conventional tissue culture plastic. We now know that the microenvironment, including the extracellular matrix and tissue architecture, plays a crucial role in directing functional differentiation of organs. Thus, in order for culture systems to be effective experimental models, they need to recapitulate the basic unit of differentiated function in the tissue or organ and to maintain its three-dimensional (3D) structure. Mouse mammary culture models evolved from basic monolayers of cells to an array of complex 3D systems that observe the importance of the microenvironment in dictating proper tissue function and structure. In this chapter, we focus on how 3D mouse mammary epithelial cultures have enabled investigators to gain a better understanding of the organization, development and function of the acinus, and to identify key molecular, structural, and mechanical cues important for maintaining mammary function and architecture. The accompanying chapter of Vidi et al. describes 3D models developed for human cells. Here, we describe how mouse primary epithelial cells and cell lines—essentially those we use in our

  14. RUNX2 in mammary gland development and breast cancer.

    PubMed

    Ferrari, Nicola; McDonald, Laura; Morris, Joanna S; Cameron, Ewan R; Blyth, Karen

    2013-06-01

    Runx2 is best known as an essential factor in osteoblast differentiation and bone development but, like many other transcription factors involved in development, is known to operate over a much wider tissue range. Our understanding of these other aspects of Runx2 function is still at a relatively early stage and the importance of its role in cell fate decisions and lineage maintenance in non-osseous tissues is only beginning to emerge. One such tissue is the mammary gland, where Runx2 is known to be expressed and participate in the regulation of mammary specific genes. Furthermore, differential and temporal expression of this gene is observed during mammary epithelial differentiation in vivo, strongly indicative of an important functional role. Although the precise nature of that role remains elusive, preliminary evidence hints at possible involvement in the regulation of mammary stem and/or progenitor cells. As with many genes important in regulating cell fate, RUNX2 has also been linked to metastatic cancer where in some established breast cell lines, retention of expression is associated with a more invasive phenotype. More recently, expression analysis has been extended to primary breast cancers where high levels of RUNX2 align with a specific subtype of the disease. That RUNX2 expression correlates with the so called "Triple Negative" subtype is particularly interesting given the known cross talk between Runx2 and estrogen receptor signaling pathways. This review summaries our current understanding of Runx2 in mammary gland development and cancer, and postulates a role that may link both these processes.

  15. Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells

    SciTech Connect

    Hirai, H.; Lochter, A.; Galosy, S.; Koshida, S.; Niwa, S.; Bissell, M.J.

    1997-10-13

    Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.

  16. Expression of maspin in mammary gland tumors of the dog.

    PubMed

    Espinosa de los Monteros, A; Millán, M Y; Ramírez, G A; Ordás, J; Reymundo, C; Martín de las Mulas, J

    2005-05-01

    Maspin is a serine protease inhibitor that inhibits tumor invasion and metastasis in human breast cancer and is consistently expressed by mammary myoepithelial cells (MECs). To analyze the value of maspin as a marker of the MEC layer of the normal and tumoral canine mammary gland, the immunohistochemical expression of maspin was studied in formalin-fixed tissues from 55 benign and malignant tumors (40 tumors also contained the surrounding normal mammary gland) using a commercially available monoclonal antibody. Periacinar and periductal MECs of all 40 normal mammary glands were stained by the anti-human maspin monoclonal antibody, and immunoreactivity was observed in the nucleus and cytoplasm of these cells. In addition, maspin was found in 53 (98%) of the tumors studied, reacting with the MECs in 100% of benign tumors and 93% of malignant tumors and to the epithelial cells of 16% of benign and 73% of malignant tumors. In the MEC compartment, immunoreactivity was observed in the cytoplasm of hypertrophic MECs, fusiform MECs, stellate MECs, rounded (myoepithelial) cells, and chondroblasts. In the epithelial cell compartment, immunoreactivity was observed in the cytoplasm of cells with and without squamous differentiation. Stromal myofibroblasts were unreactive. Maspin appears to be a very sensitive marker of the normal and neoplastic myoepithelium that, contrary to smooth muscle differentiation markers, does not stain stromal myofibroblasts. In addition, a subset of neoplastic epithelial cells reacted with the maspin antibody. The relationship between maspin expression in different cellular compartments of canine mammary carcinomas and the biologic aggressiveness of the disease remains to be elucidated.

  17. Akt is required for Stat5 activation and mammary differentiation

    PubMed Central

    2010-01-01

    Introduction The Akt pathway plays a central role in regulating cell survival, proliferation and metabolism, and is one of the most commonly activated pathways in human cancer. A role for Akt in epithelial differentiation, however, has not been established. We previously reported that mice lacking Akt1, but not Akt2, exhibit a pronounced metabolic defect during late pregnancy and lactation that results from a failure to upregulate Glut1 as well as several lipid synthetic enzymes. Despite this metabolic defect, however, both Akt1-deficient and Akt2-deficient mice exhibit normal mammary epithelial differentiation and Stat5 activation. Methods In light of the overlapping functions of Akt family members, we considered the possibility that Akt may play an essential role in regulating mammary epithelial development that is not evident in Akt1-deficient mice due to compensation by other Akt isoforms. To address this possibility, we interbred mice bearing targeted deletions in Akt1 and Akt2 and determined the effect on mammary differentiation during pregnancy and lactation. Results Deletion of one allele of Akt2 in Akt1-deficient mice resulted in a severe defect in Stat5 activation during late pregnancy that was accompanied by a global failure of terminal mammary epithelial cell differentiation, as manifested by the near-complete loss in production of the three principal components of milk: lactose, lipid, and milk proteins. This defect was due, in part, to a failure of pregnant Akt1-/-;Akt2+/- mice to upregulate the positive regulator of Prlr-Jak-Stat5 signaling, Id2, or to downregulate the negative regulators of Prlr-Jak-Stat5 signaling, caveolin-1 and Socs2. Conclusions Our findings demonstrate an unexpected requirement for Akt in Prlr-Jak-Stat5 signaling and establish Akt as an essential central regulator of mammary epithelial differentiation and lactation. PMID:20849614

  18. Noncanonical TGF-β signaling during mammary tumorigenesis.

    PubMed

    Parvani, Jenny G; Taylor, Molly A; Schiemann, William P

    2011-06-01

    Breast cancer is a heterogeneous disease comprised of at least five major tumor subtypes that coalesce as the second leading cause of cancer death in women in the United States. Although metastasis clearly represents the most lethal characteristic of breast cancer, our understanding of the molecular mechanisms that govern this event remains inadequate. Clinically, ~30% of breast cancer patients diagnosed with early-stage disease undergo metastatic progression, an event that (a) severely limits treatment options, (b) typically results in chemoresistance and low response rates, and (c) greatly contributes to aggressive relapses and dismal survival rates. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that regulates all phases of postnatal mammary gland development, including branching morphogenesis, lactation, and involution. TGF-β also plays a prominent role in suppressing mammary tumorigenesis by preventing mammary epithelial cell (MEC) proliferation, or by inducing MEC apoptosis. Genetic and epigenetic events that transpire during mammary tumorigenesis conspire to circumvent the tumor suppressing activities of TGF-β, thereby permitting late-stage breast cancer cells to acquire invasive and metastatic phenotypes in response to TGF-β. Metastatic progression stimulated by TGF-β also relies on its ability to induce epithelial-mesenchymal transition (EMT) and the expansion of chemoresistant breast cancer stem cells. Precisely how this metamorphosis in TGF-β function comes about remains incompletely understood; however, recent findings indicate that the initiation of oncogenic TGF-β activity is contingent upon imbalances between its canonical and noncanonical signaling systems. Here we review the molecular and cellular contributions of noncanonical TGF-β effectors to mammary tumorigenesis and metastatic progression.

  19. Comparative expression pathway analysis of human and canine mammary tumors

    PubMed Central

    Uva, Paolo; Aurisicchio, Luigi; Watters, James; Loboda, Andrey; Kulkarni, Amit; Castle, John; Palombo, Fabio; Viti, Valentina; Mesiti, Giuseppe; Zappulli, Valentina; Marconato, Laura; Abramo, Francesca; Ciliberto, Gennaro; Lahm, Armin; La Monica, Nicola; de Rinaldis, Emanuele

    2009-01-01

    Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies. PMID:19327144

  20. Lesions of anogenital mammary-like glands: an update.

    PubMed

    Kazakov, Dmitry V; Spagnolo, Dominic V; Kacerovska, Denisa; Michal, Michal

    2011-01-01

    Long considered to be ectopic breast tissue representing the caudal remnants of the milk ridges, anogenital mammary-like glands are nowadays thought to represent a normal constituent of the anogenital area. Lesions involving these glands, benign or malignant, epithelial or stromal manifest a striking similarity to their mammary counterparts. This review addresses the recent literature on lesions of anogenital mammary-like glands and our personal experience with various lesions related to these structures. Discussed are the normal anatomy and histology of these glands as well as the clinical presentation, histopathological and immunohistochemical features, molecular biological aspects, and differential diagnosis of various lesions involving anogenital mammary-like glands, including lactating adenoma, hidradenoma papilliferum, hidradenocarcinoma papilliferum, fibroadenomas, phyllodes tumor, pseudoangiomatous stromal hyperplasia, extramammary Paget disease, and other carcinomas. In addition, "nonspecific" epithelial or stromal changes some of which can be likened to similar changes occurring in a range of benign breast disease, including sclerosing adenosis, columnar cell lesions, ductal lesions and various metaplastic changes affecting epithelium and myoepithelium are discussed. Although lesions of anogenital mammary-like glands are often discussed in many dermatopathology textbooks in the context of cutaneous adnexal neoplasms we advocate that the best approach to the diagnosis of these lesions is to relate them to analogous well recognized lesions occurring in the breast, that is, through the eyes of a breast pathologist. This will enable their recognition, precise classification and should introduce greater uniformity in how they are reported in the literature so that more meaningful clinicopathological comparisons and correlations may be made.

  1. Noncanonical TGF-β Signaling During Mammary Tumorigenesis

    PubMed Central

    Parvani, Jenny G.; Taylor, Molly A.; Schiemann, William P.

    2013-01-01

    Breast cancer is a heterogeneous disease comprised of at least 5 major tumor subtypes that coalesce as the second leading cause of cancer death in women in the United States. Although metastasis clearly represents the most lethal characteristic of breast cancer, our understanding of the molecular mechanisms that govern this event remains wholly inadequate. Clinically, ~30% of breast cancer patients diagnosed with early-stage disease undergo metastatic progression, an event that (i) severely limits treatment options, (ii) typically results in chemoresistance and low response rates, and (iii) greatly contributes to aggressive relapses and dismal survival rates. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that regulates all phases of post-natal mammary gland development, including branching morphogenesis, lactation, and involution. TGF-β also plays a prominent role in suppressing mammary tumorigenesis by preventing mammary epithelial cell (MEC) proliferation, or by inducing MEC apoptosis. Genetic and epigenetic events that transpire during mammary tumorigenesis conspire to circumvent the tumor suppressing activities of TGF-β, thereby permitting late-stage breast cancer cells to acquire invasive and metastatic phenotypes in response to TGF-β. Metastatic progression stimulated by TGF-β also relies on its ability to induce epithelial-mesenchymal transition (EMT) and the expansion of chemoresistant breast cancer stem cells. Precisely how this metamorphosis in TGF-β function comes about remains incompletely understood; however, recent findings indicate that the initiation of oncogenic TGF-β activity is contingent upon imbalances between its canonical and noncanonical signaling systems. Here we review molecular and cellular contributions of noncanonical TGF-β effectors to mammary tumorigenesis and metastatic progression. PMID:21448580

  2. Managing heavy metal toxicity stress in plants: biological and biotechnological tools.

    PubMed

    Ovečka, M; Takáč, T

    2014-01-01

    The maintenance of ion homeostasis in plant cells is a fundamental physiological requirement for sustainable plant growth, development and production. Plants exposed to high concentrations of heavy metals must respond in order to avoid the deleterious effects of heavy metal toxicity at the structural, physiological and molecular levels. Plant strategies for coping with heavy metal toxicity are genotype-specific and, at least to some extent, modulated by environmental conditions. There is considerable interest in the mechanisms underpinning plant metal tolerance, a complex process that enables plants to survive metal ion stress and adapt to maintain growth and development without exhibiting symptoms of toxicity. This review briefly summarizes some recent cell biological, molecular and proteomic findings concerning the responses of plant roots to heavy metal ions in the rhizosphere, metal ion-induced reactions at the cell wall-plasma membrane interface, and various aspects of heavy metal ion uptake and transport in plants via membrane transporters. The molecular and genetic approaches that are discussed are analyzed in the context of their potential practical applications in biotechnological approaches for engineering increased heavy metal tolerance in crops and other useful plants. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Enhanced mammary progesterone receptor-A isoform activity in the promotion of mammary tumor progression by dietary soy in rats

    USDA-ARS?s Scientific Manuscript database

    Dietary contribution to breast cancer risk, recurrence, and progression remains incompletely understood. Increased consumption of soy and soy isoflavones is associated with reduced mammary cancer susceptibility in women and in rodent models of carcinogenesis. In rats treated with N-Methyl-N-Nitrosou...

  4. A novel non-mouse mammary tumor virus activation of the Int-3 gene in a spontaneous mouse mammary tumor.

    PubMed Central

    Kordon, E C; Smith, G H; Callahan, R; Gallahan, D

    1995-01-01

    In a mouse mammary tumor model system in which carcinogenic progression can be investigated, we have found a unique mutation of Int-3 associated with progression from premalignant lobular hyperplasia to tumor. Sequence analysis of the rearranged fragment revealed an insertion of an intracisternal type A particle (IAP) within the Int-3 gene. Int-3 is mutated frequently in mouse mammary tumor virus (MMTV)-induced mammary tumors by insertion of MMTV proviral DNA into this intragenic region. In these mutations, the insertion produces a chimeric Int-3 transcript encoding the cytoplasmic portion of the Int-3 protein driven by the MMTV long terminal repeat promoter. In this case, the IAP DNA was inserted in the opposite transcriptional orientation relative to Int-3; nevertheless, a similar chimeric RNA transcript driven by a cryptic promoter in the oppositely oriented 5' IAP long terminal repeat was generated. This is the first demonstration that an insertional mutation unrelated to MMTV activates an Int gene commonly associated with mammary tumorigenesis. PMID:7494323

  5. Analysis of the transfer RNA population of mouse mammary glands infected with a latent mammary tumor virus.

    PubMed

    Hentzen, D

    1976-09-01

    Mammary gland transfer RNA's (tRNA'S) of CEH mice infected with mammary tumor virus were analyzed in the preneoplastic state and compared to tRNAs of virus-free C3Hf mice and another uninfected strain, C57BL/6, which is completely resistant to cancer. This quantitative study was based on the ability of each tRNA to fix its corresponding amino acid. The amount of each of the 17 tRNA's tested was identical for the three mammary glands. In addition, tRNA populations during lactation correlated with the amino acids incorporated into the lactoproteins synthesized, which indicates adapation of the tRNA's to protein biosynthesis. Qualitative chromatographic studies on reverse phase capillary columns Type 5 of 10 aminoacyl-tRNA's did not reveal any difference in the isoacceptor elution profiles. This shows that no new isoaccepting tRNA is associated with the mammary tumor virus at that stage, and that no viral modification of a host tRNA has occurred.

  6. The transcriptome of estrogen-independent mammary growth reveals that not all mammary glands are created equally

    USDA-ARS?s Scientific Manuscript database

    Allometric growth of ducts in the mammary glands (MG) is widely-held to be estrogen (E)-dependent. We previously discovered that the dietary fatty acid trans-10, cis-12 conjugated linoleic acid (CLA) stimulates E-independent allometric growth and TEB formation in ovariectomized mice. Given the simil...

  7. Regulation of adipocyte lipid homeostasis by genistein alters mammary epithelial cell differentiation: a paracrine mechanism for mammary tumor protection

    USDA-ARS?s Scientific Manuscript database

    Epidemiological and animal studies have shown a negative correlation between breast cancer incidence and intake of soy rich foods. Our laboratory has studied soy protein isolate (SPI), the primary component of soy infant formula, as a paradigm to evaluate diet as a risk factor in mammary cancer. We ...

  8. Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway

    PubMed Central

    Voutilainen, Maria; Lönnblad, Darielle; Shirokova, Vera; Elo, Teresa; Rysti, Elisa; Schmidt-Ullrich, Ruth; Schneider, Pascal; Mikkola, Marja L.

    2015-01-01

    Mammary gland development commences during embryogenesis with the establishment of a species typical number of mammary primordia on each flank of the embryo. It is thought that mammary cell fate can only be induced along the mammary line, a narrow region of the ventro-lateral skin running from the axilla to the groin. Ectodysplasin (Eda) is a tumor necrosis factor family ligand that regulates morphogenesis of several ectodermal appendages. We have previously shown that transgenic overexpression of Eda (K14-Eda mice) induces formation of supernumerary mammary placodes along the mammary line. Here, we investigate in more detail the role of Eda and its downstream mediator transcription factor NF-κB in mammary cell fate specification. We report that K14-Eda mice harbor accessory mammary glands also in the neck region indicating wider epidermal cell plasticity that previously appreciated. We show that even though NF-κB is not required for formation of endogenous mammary placodes, it is indispensable for the ability of Eda to induce supernumerary placodes. A genome-wide profiling of Eda-induced genes in mammary buds identified several Wnt pathway components as potential transcriptional targets of Eda. Using an ex vivo culture system, we show that suppression of canonical Wnt signalling leads to a dose-dependent inhibition of supernumerary placodes in K14-Eda tissue explants. PMID:26581094

  9. Mammary tumor modifiers in BALB/cJ mice heterozygous for p53.

    PubMed

    Koch, Joanna G; Gu, Xiangjun; Han, Younghun; El-Naggar, Adel K; Olson, Melissa V; Medina, Daniel; Jerry, D Joseph; Blackburn, Anneke C; Peltz, Gary; Amos, Christopher I; Lozano, Guillermina

    2007-05-01

    BALB/c mice are predisposed to developing spontaneous mammary tumors, which are further increased in a p53 heterozygous state. C57BL/6J mice are resistant to induced mammary tumors and develop less than 1% mammary tumors in both wild-type and p53+/- states. To map modifiers of mammary tumorigenesis, we have established F1 and F2 crosses and backcrosses to BALB/cJ (N2-BALB/cJ) and C57BL/6J (N2-C57BL/6J) strains. All cohorts developed mammary carcinomas in p53+/- females, suggesting that multiple loci dominantly and recessively contributed to mammary tumorigenesis. We mapped two modifiers of mammary tumorigenesis in the BALB/cJ strain. Mtsm1 (mammary tumor susceptibility modifier), a dominant-acting modifier, is located on chromosome 7. Mtsm1 is suggestive for linkage to mammary tumorigenesis (p = 0.001). We have analyzed the Mtsm1 region to locate candidate genes by comparing it to a rat modifier region, Mcs3, which shares syntenic conservation with Mtsm1. Expression data and SNPs were also taken into account. Five potential candidate genes within Mtsm1 are Aldh1a3, Chd2, Nipa2, Pcsk6, and Tubgcp5. The second modifier mapped is Mtsm2, a recessive-acting modifier. Mtsm2 is located on chromosome X and is significantly linked to mammary tumorigenesis (p = 1.03 x 10(-7)).

  10. Integrin β4 regulation of PTHrP underlies its contribution to mammary gland development.

    PubMed

    Li, Jiarong; Sun, Huayan; Feltri, M Laura; Mercurio, Arthur M

    2015-11-15

    The integrin α6β4 (referred to as β4) is expressed in epithelial cells where it functions as a laminin receptor. Although in vitro studies have implicated β4 in the biology of mammary epithelial cells, its contribution to mammary gland development has not been settled. To address this problem, we generated and analyzed itgb4(flox/flox)MMTV-Cre(-) and itgb4(flox/flox)MMTV-Cre(+) mice. The salient features of embryonic mammary tissue from itgb4(flox/flox)MMTV-Cre(+) mice were significantly smaller mammary buds and increased apoptosis in the surrounding mesenchyme. Also, compared to control glands, the itgb4-deleted mammary buds lacked expression of the progenitor cell marker CK14 and they were unable to generate mammary glands upon transplantation into cleared fat pads of recipient mice. Analysis of mammary glands at puberty and during pregnancy revealed that itgb4-diminished mammary tissue was unable to elongate and undergo branching morphogenesis. Micro-dissection of epithelial cells in the mammary bud and of the surrounding mesenchyme revealed that loss of β4 resulted in a significant decrease in the expression of parathyroid hormone related protein (PTHrP) in epithelial cells and of target genes of the PTHrP receptor in mesenchymal cells. Given that the phenotype of the itgb4-deleted mammary tissue mimicked that of the PTHrP knockout, we hypothesized that β4 contributes to mammary gland development by sustaining PTHrP expression and enabling PTHrP signaling. Indeed, the inability of itgb4-deleted mammary buds to elongate was rescued by exogenous PTHrP. These data implicate a critical role for the β4 integrin in mammary gland development and provide a mechanism for this role.

  11. The prostaglandin E2 receptor EP2 is required for cyclooxygenase 2-mediated mammary hyperplasia.

    PubMed

    Chang, Sung-Hee; Ai, Youxi; Breyer, Richard M; Lane, Timothy F; Hla, Timothy

    2005-06-01

    Expression of cyclooxygenase 2 (COX-2) in breast cancer correlates with poor prognosis, and COX-2 enzyme inhibitors reduce breast cancer incidence in humans. We recently showed that COX-2 overexpression in the mammary gland of transgenic mice induced mammary cancer. Because prostaglandin E2 (PGE2) is the major eicosanoid and because the EP2 subtype of the PGE2 receptor is highly expressed in the mammary tumors, we tested if this G protein-coupled receptor is required for tumorigenesis. We crossed the MMTV-COX-2 transgenic mice with Ep2-/- mice and studied tumor development in bigenic mice. Lack of EP2 receptor strongly suppressed COX-2-induced effects such as precocious development of the mammary gland in virgins and the development of mammary hyperplasia in multiparous female mice. Interestingly, the expression of amphiregulin, a potent mammary epithelial cell growth factor was down regulated in mammary glands of Ep2-/- mice. Total cyclic AMP (cAMP) levels were reduced in Ep2-/- mammary glands suggesting that PGE2 signaling via the EP2 receptor activates the Gs/cAMP/protein kinase A pathway. In mammary tumor cell lines, expression of the EP2 receptor followed by treatment with CAY10399, an EP2-specific agonist, strongly induced amphiregulin mRNA levels in a protein kinase A-dependent manner. These data suggest that PGE2 signaling via the EP2 receptor in mammary epithelial cells regulate mammary gland hyperplasia by the cAMP-dependent induction of amphiregulin. Inhibition of the EP2 pathway in the mammary gland may be a novel approach in the prevention and/or treatment of mammary cancer.

  12. Metal Ion Induced Pairing of Cytosine Bases: Formation of I-Motif Structures Identified by IR Ion Spectroscopy

    NASA Astrophysics Data System (ADS)

    Gao, Juehan; Berden, Giel; Oomens, J.

    2015-06-01

    While the Watson-Crick structure of DNA is among the most well-known molecular structures of our time, alternative base-pairing motifs are also known to occur, often depending on base sequence, pH, or presence of cations. Pairing of two cytosine (C) bases induced by the sharing of a single proton (C-H^+-C) gives rise to the so-called i-motif, occurring particularly in the telomeric region of DNA, and particularly at low pH. At physiological pH, silver cations were recently suggested to form cytosine dimers in a C-Ag^+-C structure analogous to the hemiprotonated cytosine dimer, which was later confirmed by IR spectroscopy.^1 Here we investigate whether Ag^+ is unique in this behavior. Using infrared action spectroscopy employing the free-electron laser FELIX and a tandem mass spectrometer in combination with quantum-chemical computations, we investigate a series of C-M^+-C complexes, where M is Cu, Li and Na. The complexes are formed by electrospray ionization (ESI) from a solution of cytosine and the metal chloride salt in acetonitrile/water. The complexes of interest are mass-isolated in the cell of a FT ion cyclotron resonance mass spectrometer, where they are irradiated with the tunable IR radiation from FELIX in the 600 - 1800 wn range. Spectra in the H-stretching range are obtained with a LaserVision OPO. Both experimental spectra as well as theoretical calculations indicate that while Cu behaves as Ag, the alkali metal ions induce a clearly different dimer structure, in which the two cytosine units are parallelly displaced. In addition to coordination to the ring nitrogen atom, the alkali metal ions coordinate to the carbonyl oxygen atoms of both cytosine bases, indicating that the alkali metal ion coordination favorably competes with hydrogen bonding between the two cytosine sub-units of the i-motif like structure. 1. Berdakin, Steinmetz, Maitre, Pino, J. Phys. Chem. A 2014, 118, 3804

  13. The biology of zinc transport in mammary epithelial cells: implications for mammary gland development, lactation, and involution.

    PubMed

    McCormick, Nicholas H; Hennigar, Stephen R; Kiselyov, Kirill; Kelleher, Shannon L

    2014-03-01

    Zinc plays a critical role in a vast array of cellular functions including gene transcription, protein translation, cell proliferation, differentiation, bioenergetics, and programmed cell death. The mammary gland depends upon tight coordination of these processes during development and reproduction for optimal expansion, differentiation, and involution. For example, zinc is required for activation of matrix metalloproteinases, intracellular signaling cascades such as MAPK and PKC, and the activation of both mitochondrial-mediated apoptosis and lysosomal-mediated cell death. In addition to functional needs, during lactation the mammary gland must balance providing optimal zinc for cellular requirements with the need to secrete a substantial amount of zinc into milk to meet the requirements of the developing neonate. Finally, the mammary gland exhibits the most profound example of programmed cell death, which is driven by both apoptotic and lysosomal-mediated cell death. Two families of zinc-specific transporters regulate zinc delivery for these diverse functions. Members of the ZIP family of zinc transporters (ZIP1-14) import zinc into the cytoplasm from outside the cell or from subcellular organelles, while members of the ZnT family (ZnT1-10) export zinc from the cytoplasm. Recently, the ion channel transient receptor potential mucolipin 1 (TRPML1) has also been implicated in zinc transport. Herein, we review our current understanding of the molecular mechanisms through which mammary epithelial cells utilize zinc with a focus on the transport of zinc into discrete subcellular organelles for specific cellular functions during mammary gland development, lactation, and involution.

  14. Unilateral once daily milking locally induces differential gene expression in both mammary tissue and milk epithelial cells revealing mammary remodeling.

    PubMed

    Boutinaud, Marion; Galio, Laurent; Lollivier, Vanessa; Finot, Laurence; Wiart, Sandra; Esquerré, Diane; Devinoy, Eve

    2013-10-16

    Once daily milking reduces milk yield, but the underlying mechanisms are not yet fully understood. Local regulation due to milk stasis in the tissue may contribute to this effect, but such mechanisms have not yet been fully described. To challenge this hypothesis, one udder half of six Holstein dairy cows was milked once a day (ODM), and the other twice a day (TDM). On the 8th day of unilateral ODM, mammary epithelial cells (MEC) were purified from the milk using immunomagnetic separation. Mammary biopsies were harvested from both udder halves. The differences in transcript profiles between biopsies from ODM and TDM udder halves were analyzed by a 22k bovine oligonucleotide array, revealing 490 transcripts that were differentially expressed. The principal category of upregulated transcripts concerned mechanisms involved in cell proliferation and death. We further confirmed remodeling of the mammary tissue by immunohistochemistry, which showed less cell proliferation and more apoptosis in ODM udder halves. Gene expression analyzed by RT-qPCR in MEC purified from milk and mammary biopsies showed a common downregulation of six transcripts (ABCG2, FABP3, NUCB2, RNASE1 and 5, and SLC34A2) but also some discrepancies. First, none of the upregulated transcripts in biopsies varied in milk-purified MEC. Second, only milk-purified MEC showed significant LALBA downregulation, which suggests therefore that they correspond to a mammary epithelial cell subpopulation. Our results, obtained after unilateral milking, suggest that cell remodeling during ODM is due to a local effect, which may be triggered by milk accumulation.

  15. Aurora kinase-A overexpression in mouse mammary epithelium induces mammary adenocarcinomas harboring genetic alterations shared with human breast cancer.

    PubMed

    Treekitkarnmongkol, Warapen; Katayama, Hiroshi; Kai, Kazuharu; Sasai, Kaori; Jones, Jennifer Carter; Wang, Jing; Shen, Li; Sahin, Aysegul A; Gagea, Mihai; Ueno, Naoto T; Creighton, Chad J; Sen, Subrata

    2016-12-01

    Recent data from The Cancer Genome Atlas analysis have revealed that Aurora kinase A (AURKA) amplification and overexpression characterize a distinct subset of human tumors across multiple cancer types. Although elevated expression of AURKA has been shown to induce oncogenic phenotypes in cells in vitro, findings from transgenic mouse models of Aurora-A overexpression in mammary glands have been distinct depending on the models generated. In the present study, we report that prolonged overexpression of AURKA transgene in mammary epithelium driven by ovine β-lactoglobulin promoter, activated through multiple pregnancy and lactation cycles, results in the development of mammary adenocarcinomas with alterations in cancer-relevant genes and epithelial-to-mesenchymal transition. The tumor incidence was 38.9% (7/18) in Aurora-A transgenic mice at 16 months of age following 4-5 pregnancy cycles. Aurora-A overexpression in the tumor tissues accompanied activation of Akt, elevation of Cyclin D1, Tpx2 and Plk1 along with downregulation of ERα and p53 proteins, albeit at varying levels. Microarray comparative genomic hybridization (CGH) analyses of transgenic mouse mammary adenocarcinomas revealed copy gain of Glp1r and losses of Ercc5, Pten and Tcf7l2 loci. Review of human breast tumor transcriptomic data sets showed association of these genes at varying levels with Aurora-A gain of function alterations. Whole exome sequencing of the mouse tumors also identified gene mutations detected in Aurora-A overexpressing human breast cancers. Our findings demonstrate that prolonged overexpression of Aurora-A can be a driver somatic genetic event in mammary adenocarcinomas associated with deregulated tumor-relevant pathways in the Aurora-A subset of human breast cancer.

  16. Inhibitory Activity of YKL-40 in Mammary Epithelial Cell Differentiation and Polarization Induced by Lactogenic Hormones: A Role in Mammary Tissue Involution

    PubMed Central

    Scully, Steve; Yan, Wei; Bentley, Brooke; Cao, Qing Jackie; Shao, Rong

    2011-01-01

    We previously reported that a secreted glycoprotein YKL-40 acts as an angiogenic factor to promote breast cancer angiogenesis. However, its functional role in normal mammary gland development is poorly understood. Here we investigated its biophysiological activity in mammary epithelial development and mammary tissue morphogenesis. YKL-40 was expressed exclusively by ductal epithelial cells of parous and non-parous mammary tissue, but was dramatically up-regulated at the beginning of involution. To mimic ductal development and explore activity of elevated YKL-40 during mammary tissue regression in vivo, we grew a mammary epithelial cell line 76N MECs in a 3-D Matrigel system in the presence of lactogenic hormones including prolactin, hydrocortisone, and insulin. Treatment of 76N MECs with recombinant YKL-40 significantly inhibited acinar formation, luminal polarization, and secretion. YKL-40 also suppressed expression of E-cadherin but increased MMP-9 and cell motility, the crucial mechanisms that mediate mammary tissue remodeling during involution. In addition, engineering of 76N MECs with YKL-40 gene to express ectopic YKL-40 recapitulated the same activities as recombinant YKL-40 in the inhibition of cell differentiation. These results suggest that YKL-40-mediated inhibition of cell differentiation and polarization in the presence of lactogenic hormones may represent its important function during mammary tissue involution. Identification of this biophysiological property will enhance our understanding of its pathologic role in the later stage of breast cancer that is developed from poorly differentiated and highly invasive cells. PMID:21991364

  17. Regulation of mammary stem cell population with dietary intake of soy protein isolate reveals novel mechanisms for diet-mediated control of mammary tumorigenesis

    USDA-ARS?s Scientific Manuscript database

    Breast cancer risk is highly modified by environmental factors including diet. Previously, we showed that dietary intake of soy protein isolate (SPI) decreased mammary tumor incidence and increased mammary tumor latency in rats relative to those fed a control casein (CAS) diet, when exposed to the c...

  18. Optimization and characterization of an in vitro bovine mammary cell culture system to study regulation of milk protein synthesis and mammary differentiation

    SciTech Connect

    Talhouk, R.S.

    1988-01-01

    A long term bovine mammary cell culture system that maintains normal mammary cell function was established and optimized to study milk protein synthesis and secretion and mammary differentiation. This culture system used bovine mammary acini isolated from developing or lactating mammary gland by enzymatic dissociation, and cryopreserved until thawed and plated for growth in vitro for these studies. Cells in M199 with lactogenic hormones {plus minus} fetal calf serum (FCS) were cultured on plastic, 100ul and 500ul type I collagen, and Matrigel, or embedded within type I collagen. Cell morphology, cell number, and total TCA-precipitable {sup 35}S-labelled proteins were monitored. Milk protein ({alpha}{sub s,1}-casein, lactoferrin (LF), {alpha}-lactalbumin, and {beta}-lactoglobulin) secretion and intracellular levels were determined by an ELISA assay.

  19. Graphitic nanostripes in silicon carbide surfaces created by swift heavy ion irradiation

    NASA Astrophysics Data System (ADS)

    Ochedowski, Oliver; Osmani, Orkhan; Schade, Martin; Bussmann, Benedict Kleine; Ban-D'Etat, Brigitte; Lebius, Henning; Schleberger, Marika

    2014-06-01

    The controlled creation of defects in silicon carbide represents a major challenge. A well-known and efficient tool for defect creation in dielectric materials is the irradiation with swift (Ekin≥500 keV/amu) heavy ions, which deposit a significant amount of their kinetic energy into the electronic system. However, in the case of silicon carbide, a significant defect creation by individual ions could hitherto not be achieved. Here we present experimental evidence that silicon carbide surfaces can be modified by individual swift heavy ions with an energy well below the proposed threshold if the irradiation takes place under oblique angles. Depending on the angle of incidence, these grooves can span several hundreds of nanometres. We show that our experimental data are fully compatible with the assumption that each ion induces the sublimation of silicon atoms along its trajectory, resulting in narrow graphitic grooves in the silicon carbide matrix.

  20. Fusion-fission Study at JAEA for Heavy-element Synthesis

    NASA Astrophysics Data System (ADS)

    Nishio, K.

    Fission fragment mass distributions were measured in the heavy-ion induced fission using 238U target nucleus. The mass distribu- tions changed drastically with incident energy. The results are explained by a change of the ratio between fusion and qasifission with nuclear orientation. A calculation based on a fluctuation dissipation model reproduced the mass distributions and their inci- dent energy dependence. Fusion probability was determined in the analysis. Evaporation residue cross sections were calculated with a statistical model in the reactions of 30Si+238U and 34S+238U using the obtained fusion probability in the entrance channel. The results agree with the measured cross sections of 263,264Sg and 267,268Hs, produced by 30Si+238U and 34S+238U, respectively. It is also suggested that the sub-barrier energies can be used for heavy element synthesis.

  1. Graphitic nanostripes in silicon carbide surfaces created by swift heavy ion irradiation.

    PubMed

    Ochedowski, Oliver; Osmani, Orkhan; Schade, Martin; Bussmann, Benedict Kleine; Ban-d'Etat, Brigitte; Lebius, Henning; Schleberger, Marika

    2014-06-06

    The controlled creation of defects in silicon carbide represents a major challenge. A well-known and efficient tool for defect creation in dielectric materials is the irradiation with swift (E(kin) ≥ 500 keV/amu) heavy ions, which deposit a significant amount of their kinetic energy into the electronic system. However, in the case of silicon carbide, a significant defect creation by individual ions could hitherto not be achieved. Here we present experimental evidence that silicon carbide surfaces can be modified by individual swift heavy ions with an energy well below the proposed threshold if the irradiation takes place under oblique angles. Depending on the angle of incidence, these grooves can span several hundreds of nanometres. We show that our experimental data are fully compatible with the assumption that each ion induces the sublimation of silicon atoms along its trajectory, resulting in narrow graphitic grooves in the silicon carbide matrix.

  2. Autocrine-paracrine regulation of the mammary gland.

    PubMed

    Weaver, S R; Hernandez, L L

    2016-01-01

    The mammary gland has a remarkable capacity for regulation at a local level, particularly with respect to its main function: milk secretion. Regulation of milk synthesis has significant effects on animal and human health, at the level of both the mother and the neonate. Control by the mammary gland of its essential function, milk synthesis, is an evolutionary necessity and is therefore tightly regulated at a local level. For at least the last 60 yr, researchers have been interested in elucidating the mechanisms underpinning the mammary gland's ability to self-regulate, largely without the influence from systemic hormones or signals. By the 1960s, scientists realized the importance of milk removal in the capacity of the gland to produce milk and that the dynamics of this removal, including emptying of the alveolar spaces and frequency of milking, were controlled locally as opposed to traditional systemic hormonal regulation. Using both in vitro systems and various mammalian species, including goats, marsupials, humans, and dairy cows, it has been demonstrated that the mammary gland is largely self-regulating in its capacity to support the young, which is the evolutionary basis for milk production. Local control occurs at the level of the mammary epithelial cell through pressure and stretching negative-feedback mechanisms, and also in an autocrine fashion through bioactive factors within the milk which act as inhibitors, regulating milk secretion within the alveoli themselves. It is only within the last 20 to 30 yr that potential candidates for these bioactive factors have been examined at a molecular level. Several, including parathyroid hormone-related protein, growth factors (transforming growth factor, insulin-like growth factor, epidermal growth factor), and serotonin, are synthesized within and act upon the gland and possess dynamic receptor activity resulting in diverse effects on growth, calcium homeostasis, and milk composition. This review will focus on the

  3. Pubertal high fat diet: effects on mammary cancer development

    PubMed Central

    2013-01-01

    Introduction Epidemiological studies linking dietary fat intake and obesity to breast cancer risk have produced inconsistent results. This may be due to the difficulty of dissociating fat intake from obesity, and/or the lack of defined periods of exposure in these studies. The pubertal mammary gland is highly sensitive to cancer-causing agents. We assessed how high fat diet (HFD) affects inflammation, proliferative, and developmental events in the pubertal gland, since dysregulation of these can promote mammary tumorigenesis. To test the effect of HFD initiated during puberty on tumorigenesis, we utilized BALB/c mice, for which HFD neither induces obesity nor metabolic syndrome, allowing dissociation of HFD effects from other conditions associated with HFD. Methods Pubertal BALB/c mice were fed a low fat diet (12% kcal fat) or a HFD (60% kcal fat), and subjected to carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis. Results HFD elevated mammary gland expression of inflammatory and growth factor genes at 3 and 4 weeks of diet. Receptor activator of nuclear factor kappa-B ligand (RANKL), robustly induced at 4 weeks, has direct mitogenic activity in mammary epithelial cells and, as a potent inducer of NF-κB activity, may induce inflammatory genes. Three weeks of HFD induced a transient influx of eosinophils into the mammary gland, consistent with elevated inflammatory factors. At 10 weeks, prior to the appearance of palpable tumors, there were increased numbers of abnormal mammary epithelial lesions, enhanced cellular proliferation, increased growth factors, chemokines associated with immune-suppressive regulatory T cells, increased vascularization, and elevated M2 macrophages. HFD dramatically reduced tumor latency. Early developing tumors were more proliferative and were associated with increased levels of tumor-related growth factors, including increased plasma levels of HGF in tumor-bearing animals. Early HFD tumors also had increased

  4. The similar mammary tumour potentials in virgins and breeders of SHN mice.

    PubMed

    Nagasawa, H; Furuichi, R; Sakamoto, S; Yamamoto, K

    1993-10-01

    Spontaneous mammary tumour potential was compared between virgins and breeders of a high mammary tumour strain of SHN mice. Virgins were essentially similar to breeders in both the cumulative and the monthly incidences of mammary tumours. DNA synthesizing enzyme activities and the number and the weight of mammary tumours also differed little between groups. While the number of preneoplastic mammary hyperplastic alveolar nodules (HAN) was significantly higher in breeders than in virgins, little difference was observed between groups in the end-bud formation and the duct growth of normal glands and the growth of HAN. These results indicate that in SHN mice virgins have similar mammary tumour potential to breeders, which is much advantageous for practical use of this strain as an animal model for human breast and other types of cancers.

  5. A MOUSE MODEL OF MAMMARY HYPERPLASIA INDUCED BY ORAL HORMONE ADMINISTRATION.

    PubMed

    Sun, Li; Guo, Dong-Hui; Liu, Fei; Liu, Qian; Jiang, Ning; Sun, Yun-Feng; Cai, Li-Ping; Zheng, Hong-Xin

    2017-01-01

    Mammary hyperplasia is one of the most common benign breast disorders. Although traditional Chinese medicine has a vast experience in the treatment of mammary hyperplasia, it is not accepted widely due to its unclear mechanism. To address the mechanism, we developed a mouse model of mammary hyperplasia. We gave mice estradiol valerate tablets and progesterone capsules sequentially for one month by intragastric administration. Mice treated by this method had a series of pathological changes which are similar to those detected in women with mammary hyperplasia, including ectopic level of estradiol and progesterone in serum, hyperplasia of mammary glands and increased expression of ERα and PR. This model will facilitate the mechanical study of traditional medicine on mammary hyperplasia.

  6. Tenascin is a Stromal Marker for Epithelial Malignancy in the Mammary Gland

    NASA Astrophysics Data System (ADS)

    Mackie, Eleanor J.; Chiquet-Ehrismann, Ruth; Adams Pearson, Carolyn; Inaguma, Yutaka; Taya, Koji; Kawarada, Yoshifumi; Sakakura, Teruyo

    1987-07-01

    Tenascin is an extracellular matrix glycoprotein that is not present in the normal mature rat mammary gland. The distribution of tenascin was examined by immunohistochemistry in mammary tumors from carcinogen-treated and untreated rats, in virus-induced mammary tumors from mice, and in a variety of mammary gland lesions from humans. Tenascin was detectable in the stroma of the malignant but not of the benign tumors from all species. An inhibition ELISA, testing homogenates of rat tumors, confirmed that tenascin was present in malignant but not in benign tumors. Thus, tenascin was consistently found to be a stromal marker for epithelial malignancy in the mammary gland. It is concluded that tenascin may be involved in the interactions between the epithelial and mesenchyme-derived (stromal) components of the mammary gland, which are known to influence epithelial carcinogenesis in this organ.

  7. Similarity of GATA-3 Expression between Rat and Human Mammary Glands.

    PubMed

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Shikata, Nobuaki; Tsubura, Airo

    2014-07-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. In particular, GATA-3 is necessary for mammary gland maturation and is a useful marker in the characterization of mammary carcinoma in humans. The expression of GATA-3 protein in normal mammary glands, fibroadenomas and carcinomas was immunohistochemically compared in female rats and humans. In normal mammary glands of rats and humans, scattered luminal cells in the acini and whole ductal epithelial cells were positive for GATA-3 in the nuclei. No positive cells were detected in rat or human fibroadenomas. In rat and human mammary carcinomas, the nuclei of proliferating luminal-derived cancer cells expressed GATA-3. Therefore, GATA-3 protein is a candidate marker for mammary carcinoma in rats as well as humans.

  8. The rat mammary gland: morphologic changes as an indicator of systemic hormonal perturbations induced by xenobiotics.

    PubMed

    Lucas, Julia N; Rudmann, Daniel G; Credille, Kelly M; Irizarry, Armando R; Peter, Augustine; Snyder, Paul W

    2007-02-01

    The development and morphology of the rat mammary gland are dependent upon several hormones including estrogens, androgens, progesterone, growth hormone and prolactin. In toxicology studies, treatment with xenobiotics may alter these hormones resulting in changes in the morphology of reproductive tissues such as the mammary gland. In the rat, male and female mammary glands exhibit striking morphologic differences that can be altered secondary to hormonal perturbations. Recognizing these morphologic changes can help the pathologist predict potential xenobiotic-induced perturbations in the systemic hormonal milieu. This review examines the development of the rat mammary gland and the influence of sex hormones on the morphology of the adult male and female rat mammary gland. Specific case examples from the literature and data from our laboratory highlight the dynamic nature of the rat mammary gland in response to hormonal changes.

  9. Similarity of GATA-3 Expression between Rat and Human Mammary Glands

    PubMed Central

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Shikata, Nobuaki; Tsubura, Airo

    2014-01-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. In particular, GATA-3 is necessary for mammary gland maturation and is a useful marker in the characterization of mammary carcinoma in humans. The expression of GATA-3 protein in normal mammary glands, fibroadenomas and carcinomas was immunohistochemically compared in female rats and humans. In normal mammary glands of rats and humans, scattered luminal cells in the acini and whole ductal epithelial cells were positive for GATA-3 in the nuclei. No positive cells were detected in rat or human fibroadenomas. In rat and human mammary carcinomas, the nuclei of proliferating luminal-derived cancer cells expressed GATA-3. Therefore, GATA-3 protein is a candidate marker for mammary carcinoma in rats as well as humans. PMID:25352719

  10. Key stages in mammary gland development: the mammary end bud as a motile organ.

    PubMed

    Hinck, Lindsay; Silberstein, Gary B

    2005-01-01

    In the rodent, epithelial end buds define the tips of elongating mammary ducts. These highly motile structures undergo repeated dichotomous branching as they aggressively advance through fatty stroma and, turning to avoid other ducts, they finally cease growth leaving behind the open, tree-like framework on which secretory alveoli develop during pregnancy. This review identifies the motility of end buds as a unique developmental marker that represents the successful integration of systemic and local mammotrophic influences, and covers relevant advances in ductal growth regulation, extracellular matrix (ECM) remodeling, and cell adhesion in the inner end bud. An unexpected growth-promoting synergy between insulin-like growth factor-1 and progesterone, in which ducts elongate without forming new end buds, is described as well as evidence strongly supporting self-inhibition of ductal elongation by end-bud-secreted transforming growth factor-beta acting on stromal targets. The influence of the matrix metalloproteinase ECM-remodeling enzymes, notably matrix metalloproteinase-2, on end bud growth is discussed in the broader context of enzymes that regulate the polysaccharide-rich glycosaminoglycan elements of the ECM. Finally, a critical, motility-enabling role for the cellular architecture of the end bud is identified and the contribution of cadherins, the netrin/neogenin system, and ErbB2 to the structure and motility of end buds is discussed.

  11. The effects of heavy ion radiation on digital micromirror device performance

    NASA Astrophysics Data System (ADS)

    Travinsky, Anton; Vorobiev, Dmitry; Ninkov, Zoran; Raisanen, Alan D.; Pellish, Jonathan A.; Robberto, Massimo; Heap, Sara

    2016-07-01

    There is a pressing need in the astronomical community for space-suitable multi-object spectrometers (MOSs). Several digital micromirror device (DMD)-based prototype MOSs have been developed for ground-based observatories; however, their main use will come with deployment on a space based mission. Therefore, performance of DMDs under exoatmospheric radiation needs to be evaluated. In our previous work we demonstrated that DMDs are tolerant to heavy ion irradiation in general and calculated upset rate of 4.3 micromirrors in 24 hours in orbit for 1-megapixel device. The goal of this additional experiment was to acquire more data and therefore increase the accuracy of the predicted in-orbit micromirror upset rate. Similar to the previous experiment, for this testing 0.7 XGA DMDs were re-windowed with 2 μm thick pellicle and tested under accelerated heavy-ion radiation (with control electronics shielded from radiation) with a focus on detection of single-event upsets (SEUs). We concentrated on ions with low levels of linear energy transfer (LET) 1.8 - 13 MeV•cm2•mg-1 to cover the most critical range of the Weibull curve for those devices. As during the previous experiment, we observed and documented non-destructive heavy ion-induced micromirror state changes. All SEUs were always cleared with a soft reset (that is, sending a new pattern to the device). The DMDs we tested did not experience single-event induced permanent damage or functional changes that required a hard reset (power cycle), even at high ion fluences. Based on the data obtained in the experiments we predict micromirror in-orbit upset rate of 5.6 micromirrors in 24 hours in-orbit for the tested devices. This suggests that the heavy-ion induced SEU rate burden for a DMD-based instrument will be manageable when exposed to solar particle fluxes and cosmic rays in orbit.

  12. A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor.

    PubMed Central

    Mink, S; Härtig, E; Jennewein, P; Doppler, W; Cato, A C

    1992-01-01

    Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus involved in the neoplastic transformation of mouse mammary gland cells. The expression of this virus is regulated by mammary cell type-specific factors, steroid hormones, and polypeptide growth factors. Sequences for mammary cell-specific expression are located in an enhancer element in the extreme 5' end of the long terminal repeat region of this virus. This enhancer, when cloned in front of the herpes simplex thymidine kinase promoter, endows the promoter with mammary cell-specific response. Using functional and DNA-protein-binding studies with constructs mutated in the MMTV long terminal repeat enhancer, we have identified two main regulatory elements necessary for the mammary cell-specific response. These elements consist of binding sites for a transcription factor in the family of CTF/NFI proteins and the transcription factor mammary cell-activating factor (MAF) that recognizes the sequence G Pu Pu G C/G A A G G/T. Combinations of CTF/NFI- and MAF-binding sites or multiple copies of either one of these binding sites but not solitary binding sites mediate mammary cell-specific expression. The functional activities of these two regulatory elements are enhanced by another factor that binds to the core sequence ACAAAG. Interdigitated binding sites for CTF/NFI, MAF, and/or the ACAAAG factor are also found in the 5' upstream regions of genes encoding whey milk proteins from different species. These findings suggest that mammary cell-specific regulation is achieved by a concerted action of factors binding to multiple regulatory sites. Images PMID:1328867

  13. Heavy quark masses

    NASA Technical Reports Server (NTRS)

    Testa, Massimo

    1990-01-01

    In the large quark mass limit, an argument which identifies the mass of the heavy-light pseudoscalar or scalar bound state with the renormalized mass of the heavy quark is given. The following equation is discussed: m(sub Q) = m(sub B), where m(sub Q) and m(sub B) are respectively the mass of the heavy quark and the mass of the pseudoscalar bound state.

  14. Role of the EGF-Related Growth Factor cripto in Murine Mammary Tumorigenesis

    DTIC Science & Technology

    2000-10-01

    activities of EGF-CFC proteins through analysis of knock-out mice for Cripto and Cryptic (reviewed in (Shen and Schier, 2000); see appendix). We have...Generation and analysis of Cripto transgenic mice Rationale: To investigate the effects of Cripto on mammary development and oncogenesis, we...phenotype at different stages of mammary development, thereby accomplishing tasks 1-5 of our Statement of Work. Analysis of whole-mounts of mammary fat pads

  15. [THE ROLE OF ENDOSCOPIC MAMMODUCTOSCOPY IN COMPLEX DIAGNOSIS OF INTRADUCTAL TUMORS OF MAMMARY GLAND].

    PubMed

    Aksyonov, O A

    2015-11-01

    First Ukrainian experience in endoscopic mammoductoscopy (EMDS) conduction in 112 patients for revealing of intraductal tumors of mammary gland is presented. In comparison with roentgenological, ultrasonographic and cytological diagnostical methods, EMDS for intraductal tumors of mammary gland differs by highest sensitivity (90.3%) and accuracy (80.2%), but insufficient (47.4%) specificity. To improve the surgical treatment results the authors propose their own method of marking of the mammary gland intraductal tumors under endoscopic and echographic control.

  16. Canonical Wnt Signaling as a Specific Marker of Normal and Tumorigenic Mammary Stem Cells

    DTIC Science & Technology

    2013-02-01

    mammary epithelium impacts glandular development . We found ductal abnormali ties; however, the phenotype was not as severe as expected. Approximately...In previous reports we have clearly showed that cells w ith activated canonical Wnt signaling are present within the mammary epithelium starting at...Wnt1 transgenic cells. We generated a mouse line in which ~-catenin is conditionally deleted in the mammary epithelium of MMTV-Wnt1 transgenic

  17. Role of Fibroblast Growth Factor Binding Protein-1 in Mammary Development and Tumorigenesis

    DTIC Science & Technology

    2009-10-01

    Hens and Wysolmerski 2005). At the future site of each nipple , five disk-like placodes line up and invade into the underlying mesenchyme. Referred...mouse mammary gland forms a single ductal tree leading to each nipple . The nascent mammary gland remains quiescent until puberty where the...harvested as described in this original proposal. 12 Apoptosis at regular intervals is a normal part of mammary physiology . In murine models

  18. Role of the Stem Cell Niche in Hormone-Induced Tumorigenesis in Fetal Mouse Mammary Epithelium

    DTIC Science & Technology

    2005-08-01

    AD Award Number: W81XWH-04-1-0719 TITLE: Role of the Stem Cell Niche in Hormone-Induced Tumorigenesis in Fetal Mouse Mammary Epithelium PRINCIPAL...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Role of the Stem Cell Niche in Hormone-induced Tumorigenesis in Fetal Mouse 5b. GRANT NUMBER Mammary Epithelium...SUPPLEMENTARY NOTES 14. ABSTRACT SEE PAGE 4 15. SUBJECT TERMS Stem Cells , Stem Cell niche, Immunohistochemistry, mammary gland, breast cancer 16

  19. Regulation of Mammary Tumor Formation and Lipid Biosynthesis by Spot14

    DTIC Science & Technology

    2011-10-01

    requirement of S14 for mammary tumor growth and cellular lipid metabolism. mammary tumor, breast cancer, Spot 14, lipid synthesis 18 elizabeth.wellberg...promote tumor formation, cell proliferation, and lipid synthesis in ErbB2 expressing mammary epithelial cells. During Year 1, we began breeding MMTV-S14...glycolysis. Less well appreciated are the high rates of de novo lipid synthesis displayed by many tumors. Two related prognostic indicators are fatty acid

  20. Investigating the Role of FIP200 in Mammary Carcinogenesis Using a Transgenic Mouse Model

    DTIC Science & Technology

    2007-04-01

    the mammary gland of virgin mice however, lactating mice have severe lobulo-alveolar hypoplasia in the mammary gland. After completing the analysis... hypoplasia which renders the dams unable to lactate). In the 1B mating scheme a female mouse with FAKFlox/Flox genotype was mated to a male MMTV...Epithelial-Specific Deletion of the Focal Adhesion Kinase Gene Leads to Severe Lobulo-Alveolar Hypoplasia and Secretory Immaturity of the Murine Mammary

  1. Induction of a Pregnancy-Like Mammary Gland Differentiation by Docosapentaenoic Omega-3 Fatty Acid

    DTIC Science & Technology

    2008-09-01

    xylenes, and stored in methyl salicylate . Morphological Assessment of Mammary Gland—Whole inguinal mammary glands were removed from virgin control as...respectively, defatted in xylenes, and stored in methyl salicylate . Quantitative RT-PCR analyses RNA was isolated and subjected to real time PCR analysis... methylation , and fatty acid analysis were performed as previously described [28,48]. Briefly, an ali- quot of mammary tissue homogenate in a glass

  2. X-ray photoelectron and X-ray Auger electron spectroscopy studies of heavy ion irradiated C 60 films

    NASA Astrophysics Data System (ADS)

    Kumar, Amit; Singh, F.; Govind; Shivaprasad, S. M.; Avasthi, D. K.; Pivin, J. C.

    2008-09-01

    The influence of 200 MeV Au ion irradiation on the surface properties of polycrystalline fullerene films has been investigated. The X-ray photoelectron and X-ray Auger electron spectroscopies are employed to study the ion-induced modification of the fullerene, near the surface region. The shift of C 1s core level and decrease in intensity of shake-up satellite were used to investigate the structural changes (like sp 2 to sp 3 conversion) and reduction of π electrons, respectively, under heavy ion irradiation. Further, X-ray Auger electron spectroscopy was employed to investigate hybridization conversion qualitatively as a function of ion fluence.

  3. Production of heavy water

    DOEpatents

    Spencer, Larry S.; Brown, Sam W.; Phillips, Michael R.

    2017-06-06

    Disclosed are methods and apparatuses for producing heavy water. In one embodiment, a catalyst is treated with high purity air or a mixture of gaseous nitrogen and oxygen with gaseous deuterium all together flowing over the catalyst to produce the heavy water. In an alternate embodiment, the deuterium is combusted to form the heavy water. In an alternate embodiment, gaseous deuterium and gaseous oxygen is flowed into a fuel cell to produce the heavy water. In various embodiments, the deuterium may be produced by a thermal decomposition and distillation process that involves heating solid lithium deuteride to form liquid lithium deuteride and then extracting the gaseous deuterium from the liquid lithium deuteride.

  4. Modeling and analysis of transport in the mammary glands

    NASA Astrophysics Data System (ADS)

    Quezada, Ana; Vafai, Kambiz

    2014-08-01

    The transport of three toxins moving from the blood stream into the ducts of the mammary glands is analyzed in this work. The model predictions are compared with experimental data from the literature. The utility of the model lies in its potential to improve our understanding of toxin transport as a pre-disposing factor to breast cancer. This work is based on a multi-layer transport model to analyze the toxins present in the breast milk. The breast milk in comparison with other sampling strategies allows us to understand the mass transport of toxins once inside the bloodstream of breastfeeding women. The multi-layer model presented describes the transport of caffeine, DDT and cimetidine. The analysis performed takes into account the unique transport mechanisms for each of the toxins. Our model predicts the movement of toxins and/or drugs within the mammary glands as well as their bioaccumulation in the tissues.

  5. Giant venous aneurysm jeopardising internal mammary arterial graft patency.

    PubMed

    Van Caenegem, Olivier; le Polain de Waroux, Jean-Benoit; de Kerchove, Laurent; Coche, Emmanuel

    2012-09-01

    The authors report a 79-year old man with a history of coronary bypass surgery, presenting with acute heart failure and elevated troponin. Coronarography revealed a giant saphenous vein graft aneurysm, which was compressing the left internal mammary artery bypass graft. This was confirmed by a multislice enhanced-ECG gated cardiac CT, showing the venous aneurysm responsible for external compression of the arterial graft and its functional occlusion. Myocardial ischaemia, the mechanism leading to cardiac failure, was confirmed by hypoperfusion of the sub-endocardial area shown by the CT. The aneurysm was surgically removed without complications. The patient recovered and his cardiac function improved. This is the first recorded case of compression of the left internal mammary artery by an giant saphenous vein graft aneurysm having triggered severe myocardial ischaemia and heart failure. The authors review the incidence and complications of giant venous bypass graft aneurysms reported in the literature.

  6. Giant venous aneurysm jeopardising internal mammary arterial graft patency

    PubMed Central

    Van Caenegem, Olivier; le Polain de Waroux, Jean-Benoit; de Kerchove, Laurent; Coche, Emmanuel

    2012-01-01

    The authors report a 79-year old man with a history of coronary bypass surgery, presenting with acute heart failure and elevated troponin. Coronarography revealed a giant saphenous vein graft aneurysm, which was compressing the left internal mammary artery bypass graft. This was confirmed by a multislice enhanced-ECG gated cardiac CT, showing the venous aneurysm responsible for external compression of the arterial graft and its functional occlusion. Myocardial ischaemia, the mechanism leading to cardiac failure, was confirmed by hypoperfusion of the sub-endocardial area shown by the CT. The aneurysm was surgically removed without complications. The patient recovered and his cardiac function improved. This is the first recorded case of compression of the left internal mammary artery by an giant saphenous vein graft aneurysm having triggered severe myocardial ischaemia and heart failure. The authors review the incidence and complications of giant venous bypass graft aneurysms reported in the literature. PMID:22723090

  7. Mammary gland tumor formation in transgenic mice overexpressing stromelysin-1

    SciTech Connect

    Sympson, Carolyn J; Bissell, Mina J; Werb, Zena

    1995-06-01

    An intact basement membrane (BM) is essential for the proper function, differentiation and morphology of many epithelial cells. The disruption or loss of this BM occurs during normal development as well as in the disease state. To examine the importance of BM during mammary gland development in vivo, we generated transgenic mice that inappropriately express autoactivating isoforms of the matrix metalloproteinase stromelysin-1. The mammary glands from these mice are both functionally and morphologically altered throughout development. We have now documented a dramatic incidence of breast tumors in several independent lines of these mice. These data suggest that overexpression of stromelysin-1 and disruption of the BM may be a key step in the multi-step process of breast cancer.

  8. Control of Differentiation of a Mammary Cell Line by Lipids

    NASA Astrophysics Data System (ADS)

    Dulbecco, Renato; Bologna, Mauro; Unger, Michael

    1980-03-01

    A rat mammary cell line (LA7) undergoes spontaneous differentiation into domes due to production of specific inducers by the cells. Some of these inducers may be lipids, and we show that lipids regulate this differentiation as both inducers and inhibitors. One inhibitor is the tumor promoter tetradecanoyl-13 phorbol 12-acetate. The inducers are saturated fatty acids of two groups: butyric acid and acids with chain lengths from C13 to C16, especially myristic acid (C14). Other inducers are myristoyl and palmitoyl lysolecithins, myristic acid methyl ester, and two cationic detergents with a tetradecenyl chain. We propose that the lipids with a C14-C16 alkyl chain affect differentiation by recognizing specific receptors through their alkyl chains and that the effects obtained depend on the head groups. These lipids may be physiological regulators in the mammary gland.

  9. Mammary gland tumors in irradiated and untreated guinea pigs

    SciTech Connect

    Hoch-Ligeti, C.; Liebelt, A.G.; Congdon, C.C.; Stewart, H.L.

    1986-01-01

    This is a report of mammary gland tumors from 62 guinea pigs. The tumors arose in the terminal ductal-lobular units as either lobular acinar carcinoma or cystadenocarcinoma or as papillary carcinomas within large ducts near the mammilla. About half the number of the males had terminal ductal-lobular carcinomas and all but 2 of the papillary duct carcinomas also arose in males. Large tumors frequently exhibited squamous, chondromatous, osseous, fatty and myoepitheliomatous types of tissues. In 2 irradiated males and 1 female the tumors metastasized. Whole-body irradiation did not produce significant changes in the number or sex distribution or in the morphology of mammary gland tumors in inbred or outbred guinea pigs. All females had cystic ovaries without increase in granulosa cells, 24 (66.6%) had uterine tumors and 13 (34.2%) had adrenal gland tumors; all males had atrophic testes, 5 (16.5%) had testicular and 6 (22.2%) had adrenal gland tumors.

  10. Ocular melanoma and mammary mucinous carcinoma in an African lion

    PubMed Central

    2012-01-01

    Background Reports of neoplasms in Panthera species are increasing, but they are still an uncommon cause of disease and death in captive wild felids. The presence of two or more primary tumor in large felids is rarely reported, and there are no documented cases of ocular melanoma and mammary mucinous carcinoma in African lions. Case presentation An ocular melanoma and a mammary mucinous carcinoma are described in an African lion (Panthera leo). The first tumour was histologically characterized by the presence of epithelioid and fusiform melanocytes, while the latter was composed of mucus-producing cells with an epithelial phenotype that contained periodic acid-Schiff (PAS) and Alcian blue staining mucins. Metastases of both tumor were identified in various organs and indirect immunohistochemistry was used to characterize them. Peribiliary cysts were observed in the liver. Conclusions This is the first description of these tumor in African lions. PMID:23009723

  11. Significance of rat mammary tumors for human risk assessment.

    PubMed

    Russo, Jose

    2015-02-01

    We have previously indicated that the ideal animal tumor model should mimic the human disease. This means that the investigator should be able to ascertain the influence of host factors on the initiation of tumorigenesis, mimic the susceptibility of tumor response based on age and reproductive history, and determine the response of the tumors induced to chemotherapy. The utilization of experimental models of mammary carcinogenesis in risk assessment requires that the influence of ovarian, pituitary, and placental hormones, among others, as well as overall reproductive events are taken into consideration, since they are important modifiers of the susceptibility of the organ to neoplastic development. Several species, such as rodents, dogs, cats, and monkeys, have been evaluated for these purposes; however, none of them fulfills all the criteria specified previously. Rodents, however, are the most widely used models; therefore, this work will concentrate on discussing the rat rodent model of mammary carcinogenesis.

  12. Serotoninergic and Circadian Systems: Driving Mammary Gland Development and Function

    PubMed Central

    Suárez-Trujillo, Aridany; Casey, Theresa M.

    2016-01-01

    Since lactation is one of the most metabolically demanding states in adult female mammals, beautifully complex regulatory mechanisms are in place to time lactation to begin after birth and cease when the neonate is weaned. Lactation is regulated by numerous different homeorhetic factors, all of them tightly coordinated with the demands of milk production. Emerging evidence support that among these factors are the serotonergic and circadian clock systems. Here we review the serotoninergic and circadian clock systems and their roles in the regulation of mammary gland development and lactation physiology. We conclude by presenting our hypothesis that these two systems interact to accommodate the metabolic demands of lactation and thus adaptive changes in these systems occur to maintain mammary and systemic homeostasis through the reproductive cycles of female mammals. PMID:27471474

  13. [Irradiation of internal mammary nodes: State of the art].

    PubMed

    Kirova, Y M; de Almeida, C E; Fournier-Bidoz, N

    2015-06-01

    In the adjuvant breast cancer treatment, postoperative radiotherapy plays a principal part with an action against the microscopic residual disease in the lymph nodes after mastectomy as well as after breast conserving surgery. This positive effect is observed also in the case of small inner lesions in patients without lymph node involvement. At the same time, there is a recognized risk of cardiac toxicity directly related to the irradiation of internal mammary nodes. This paper is a report on the current available techniques to irradiate the internal mammary nodes, including promising new technology that may help limiting the risk of cardiac toxicity. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  14. MAMMARY GLAND ADENOCARCINOMA IN A MALE BORNEAN ORANGUTAN (PONGO PYGMAEUS).

    PubMed

    Carpenter, Nancy A; Crook, Erika K

    2017-03-01

    An adult male Bornean orangutan ( Pongo pygmaeus ) was diagnosed with invasive, poorly differentiated grade 9/9 mammary gland adenocarcinoma from a subcutaneous mass that was surgically removed during a routine preventative health examination. The tumor was tested for estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and HER2 fluorescence in situ hybridization (HER2 FISH). Whole blood was tested for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. The orangutan was treated orally with two common human breast cancer drugs; tamoxifen and anastrozole. The orangutan lived for 4.5 yr postdetection, dying from an unrelated cause. This is the first reported case of mammary gland adenocarcinoma in a male great ape.

  15. Ocular melanoma and mammary mucinous carcinoma in an African lion.

    PubMed

    Cagnini, Didier Q; Salgado, Breno S; Linardi, Juliana L; Grandi, Fabrizio; Rocha, Rafael M; Rocha, Noeme S; Teixeira, Carlos R; Del Piero, Fabio; Sequeira, Julio L

    2012-09-25

    Reports of neoplasms in Panthera species are increasing, but they are still an uncommon cause of disease and death in captive wild felids. The presence of two or more primary tumor in large felids is rarely reported, and there are no documented cases of ocular melanoma and mammary mucinous carcinoma in African lions. An ocular melanoma and a mammary mucinous carcinoma are described in an African lion (Panthera leo). The first tumour was histologically characterized by the presence of epithelioid and fusiform melanocytes, while the latter was composed of mucus-producing cells with an epithelial phenotype that contained periodic acid-Schiff (PAS) and Alcian blue staining mucins. Metastases of both tumor were identified in various organs and indirect immunohistochemistry was used to characterize them. Peribiliary cysts were observed in the liver. This is the first description of these tumor in African lions.

  16. Failure of bromocriptine therapy to control juvenile mammary hypertrophy.

    PubMed

    Arscott, G D; Craig, H R; Gabay, L

    2001-12-01

    Rapid massive breast hypertrophy occasionally occurs at the time of puberty or during pregnancy, with breast size eventually becoming burdensome or incapacitating to the patient. Pregnancy-related breast hypertrophy is often arrested or reversed by reducing serum prolactin levels with bromocriptine therapy. Unfortunately, breast enlargement in our 12-year-old patient with massive juvenile mammary hypertrophy was unaffected by bromocriptine therapy despite a reduction of her prolactin to normal levels. Two reduction mammaplasties followed by subcutaneous mastectomy were required to control breast hypertrophy. Breast-tissue hypersensitivity to prolactin appears to be a characteristic of pregnancy-related gigantomastia. Our pubertal patient with juvenile mammary hypertrophy failed to respond to bromocriptine therapy, so the aetiology of this syndrome may involve breast-tissue hypersensitivity to hormones other than prolactin. Copyright 2001 The British Association of Plastic Surgeons.

  17. Quantification of regenerative potential in primary human mammary epithelial cells.

    PubMed

    Linnemann, Jelena R; Miura, Haruko; Meixner, Lisa K; Irmler, Martin; Kloos, Uwe J; Hirschi, Benjamin; Bartsch, Harald S; Sass, Steffen; Beckers, Johannes; Theis, Fabian J; Gabka, Christian; Sotlar, Karl; Scheel, Christina H

    2015-09-15

    We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49f(hi)/EpCAM(-) population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis.

  18. Quantification of regenerative potential in primary human mammary epithelial cells

    PubMed Central

    Linnemann, Jelena R.; Miura, Haruko; Meixner, Lisa K.; Irmler, Martin; Kloos, Uwe J.; Hirschi, Benjamin; Bartsch, Harald S.; Sass, Steffen; Beckers, Johannes; Theis, Fabian J.; Gabka, Christian; Sotlar, Karl; Scheel, Christina H.

    2015-01-01

    We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49fhi/EpCAM− population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis. PMID:26071498

  19. Modeling and analysis of transport in the mammary glands.

    PubMed

    Quezada, Ana; Vafai, Kambiz

    2014-08-01

    The transport of three toxins moving from the blood stream into the ducts of the mammary glands is analyzed in this work. The model predictions are compared with experimental data from the literature. The utility of the model lies in its potential to improve our understanding of toxin transport as a pre-disposing factor to breast cancer. This work is based on a multi-layer transport model to analyze the toxins present in the breast milk. The breast milk in comparison with other sampling strategies allows us to understand the mass transport of toxins once inside the bloodstream of breastfeeding women. The multi-layer model presented describes the transport of caffeine, DDT and cimetidine. The analysis performed takes into account the unique transport mechanisms for each of the toxins. Our model predicts the movement of toxins and/or drugs within the mammary glands as well as their bioaccumulation in the tissues.

  20. Establishment and Characterization of a Buffalo (Bubalus bubalis) Mammary Epithelial Cell Line

    PubMed Central

    Anand, Vijay; Dogra, Nilambra; Singh, Surender; Kumar, Sudarshan N.; Jena, Manoj K.; Malakar, Dhruba; Dang, Ajay K.; Mishra, Bishnu P.; Mukhopadhyay, Tapas K.; Kaushik, Jai K.; Mohanty, Ashok K.

    2012-01-01

    Background The objective of this study was to establish the buffalo mammary epithelial cell line (BuMEC) and characterize its mammary specific functions. Methodology Buffalo mammary tissue collected from the slaughter house was processed enzymatically to obtain a heterogenous population of cells containing both epithelial and fibroblasts cells. Epithelial cells were purified by selective trypsinization and were grown in a plastic substratum. The purified mammary epithelial cells (MECs) after several passages were characterized for mammary specific functions by immunocytochemistry, RT-PCR and western blot. Principal Findings The established buffalo mammary epithelial cell line (BuMEC) exhibited epithelial cell characteristics by immunostaining positively with cytokeratin 18 and negatively with vimentin. The BuMEC maintained the characteristics of its functional differentiation by expression of β-casein, κ-casein, butyrophilin and lactoferrin. BuMEC had normal growth properties and maintained diploid chromosome number (2n = 50) before and after cryopreservation. A spontaneously immortalized buffalo mammary epithelial cell line was established after 20 passages and was continuously subcultured for more than 60 passages without senescence. Conclusions We have established a buffalo mammary epithelial cell line that can be used as a model system for studying mammary gland functions. PMID:22792341