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  • 1
    Electronic Resource
    Electronic Resource
    The biology of the P-glycoproteins (1995)
    Springer
    The journal of membrane biology 143 (1995), S. 89-102 
    Details
    ISSN: 1432-1424
    Keywords: Drug resistance ; ATPases ; Chemotherapy ; Cancer ; Membrane Transport ; Xenobiotics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Conclusions The initial discovery of p-glycoprotein in the plasma membrane of MDR cancer cell lines was followed quickly by the cloning of its gene. Sequence analysis of cloned cDNAs revealed that p-glycoprotein was a member of the ABC family of membrane transporters. Subsequent biochemical characterization demonstrated the binding of chemotherapeutic drugs and ATP to p-glycoprotein. P-glycoprotein-mediated drag transport and drug-stimulated ATPase activity were documented in plasma membrane vesicles and in proteoliposomes containing the partially purified protein. P-glycoprotein was shown to be phosphorylated and the effect of this modification on the protein's biological function was explored. P-glycoproteins were found in many normal tissues and their overexpression was documented in numerous cancers. An important role for p-glycoprotein in intrinsic and acquired drug resistance in clinical oncology was established. Despite all that has been learned about p-glycoprotein over the last few years, additional studies will be necessary to address the many questions that have been left unanswered. Determination of p-glycoprotein structure and membrane topology should help elucidate the nature of chemotherapeutic drug binding sites and the mechanism whereby drug movement is coupled to ATP hydrolysis. Complete purification and functional reconstitution of p-glycoprotein into defined lipid vesicles will permit further characterization of drug transport and ATPase activity and give us the means by which p-glycoprotein's apparent dual function as a transporter and a channel can be clarified. Structural and functional studies on p-glycoprotein will also provide information needed to develop specified inhibitors that can be used clinically to overcome MDR in cancer patients. Further study of the mechanisms whereby p-glycoprotein expression is induced and regulated during malignant transformation is indicated. The development of biliary phospholipid deficiency in mdr2 knockout mice and xenobiotic hypersensitivity in mdr3 knockout mice have given us the first clues into the normal physiologic roles for the p-glycoproteins. The search for endogenous substrates for the p-glycoproteins will continue to be an area of active investigation. Continued investigation of p-glycoprotein's functions should result in better understanding of an important class of prokaryotic and eukaryotic membrane transporters. The potential of exploiting the knowledge garnered from these studies in the treatment of neoplastic, parasitic and inherited and acquired liver disease may be greater than we can now imagine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00234655
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    Paper (German National Licenses)
    Fulltext
  • 2
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    Growth of Lower Stratospheric HCl/Cly Since 1993: Observations from Aircraft (ALIAS), Balloon (MarkIV, FIRS-2), Space Shuttle (ATMOS), and Satellite (HALOE) Measurements (1998)
    In:  Other Sources
    Details
    Publication Date: 2018-06-08
    Description: Measurements of HCl in the lower stratosphere (15-21 km) from aircraft, balloon, Space Shuttle, and satellite reveal a growth in its mean abundance relative to that of total inorganic chlorine (Cly) from HCl/Cly = 57(+/-5)% in early 1993 to 75(+/-7)% by the end of 1997.
    Keywords: Geophysics
    Type: Geophysical Research Letters
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  • 3
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    Tropical Entrainment Time Sclaes Inferred from Stratospheric N(sub 2)0 and CH(sub 4) Observations (1998)
    In:  Other Sources
    Details
    Publication Date: 2018-06-08
    Description: Simultaneous in situ measurements of the long-lived trace gases N(sub 2)O and CH(sub 4) were made with a tunable diode laser spectrometer (ALIAS II) aboard the Observations from the Middle Stratosphere (OMS) balloon platform from New Mexico, Alaska, and Brazil during 1996 and 1997.
    Keywords: Geophysics
    Type: Geophysical Research Letters
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  • 4
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    Isotopic Composition of Carbon Dioxide Released from Confidence Hills Sediment as Measured by the Sample Analysis at Mars (SAM) Quadrupole Mass Spectrometer (2015)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: In October 2014, the Mars Science Laboratory (MSL) "Curiosity" rover drilled into the sediment at the base of Mount Sharp in a location namsed Cionfidence Hills (CH). CH marked the fifth sample pocessed by the Sample Analysis at Mars (SAM) instrument suite since Curiosity arrived in Gale Crater, with previous analyses performed at Rocknest (RN), John Klein (JK), Cumberland (CB), and Windjana (WJ). Evolved gas analysis (EGA) of all samples has indicated H2O as well as O-, C- and S-bearing phases in the samples, often at abundances that would be below the detection limit of the CheMin instrument. By examining the temperatures at which gases are evolved from samples, SAM EGA data can help provide clues to the mineralogy of volatile-bearing phases when their identities are unclear to CheMin. SAM may also detect gases evolved from amorphous material in solid samples, which is not suitable for analysis by CheMin. Finally, the isotopic composition of these gases may suggest possible formation scenarios and relationships between phases. We will discuss C isotope ratios of CO2 evolved from the CH sample as measured with SAM's quadrupole mass spectrometer (QMS) and draw comparisons to samples previously analyzed by SAM.
    Keywords: Geophysics
    Type: JSC-CN-32850 , Lunar and Planetary Science Conference; Mar 16, 2015 - Mar 20, 2015; The Woodlands, TX; United States
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  • 5
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    The Diurnal Variation of Hydrogen, Nitrogen, and Chlorine Radicals: Implications for the Heterogeneous Production of HNO2 (1994)
    In:  CASI
    Details
    Publication Date: 2019-08-17
    Description: In situ measurements of hydrogen, nitrogen, and chlorine radicals obtained through sunrise and sunset in the lower stratosphere during SPADE are compared to results from a photochemical model constrained by observed concentrations of radical precursors and environmental conditions. Models allowing for heterogeneous hydrolysis of N205 on sulfate aerosols agree with measured concentrations of NO, NO2, and ClO throughout the day, but fail to account for high concentrations of OH and H02 observed near sunrise and sunset. The morning burst of [OH] and [HO2] coincides with the rise of [NO] from photolysis of N02, suggesting a new source of HO, that photolyzes in the near UV (350 to 400 nm) spectral region. A model that allows for the heterogeneous production of HN02 results in an excellent simulation of the diurnal variations of [OH] and [HO2].
    Keywords: Geophysics
    Type: NASA-CR-204900 , Paper-94-GL-02782 , NAS 1.26:204900 , Geophysical Research Letters (ISSN 0094-8534); 21; 23; 2551-2554
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  • 6
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    Hydrogen Radicals, Nitrogen Radicals, and the Production of O3 in the Upper Troposphere (1998)
    In:  Other Sources
    Details
    Publication Date: 2019-08-17
    Description: The concentrations of the hydrogen radicals OH and HO2 in the middle and upper troposphere were measured simultaneously with those of NO, O3, CO, H2O, CH4, non-methane hydrocarbons, and with the ultraviolet and visible radiation field. The data allow a direct examination of the processes that produce O3 in this region of the atmosphere. Comparison of the measured concentrations of OH and HO2 with calculations based on their production from water vapor, ozone, and methane demonstrate that these sources are insufficient to explain the observed radical concentrations in the upper troposphere. The photolysis of carbonyl and peroxide compounds transported to this region from the lower troposphere may provide the source of HO, required to sustain the measured abundances of these radical species. The mechanism by which NO affects the production Of O3 is also illustrated by the measurements. In the upper tropospheric air masses sampled, the production rate for ozone (determined from the measured concentrations of HO2 and NO) is calculated to be about I part per billion by volume each day. This production rate is faster than previously thought and implies that anthropogenic activities that add NO to the upper troposphere, such as biomass burning and aviation, will lead to production of more 03 than expected.
    Keywords: Geophysics
    Type: Science; 279; 49-53
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  • 7
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    Carbon and Sulfur Isotopic Composition of Rocknest Soil as Determined with the Sample Analysis at Mars(SAM) Quadrupole Mass Spectrometer (2013)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: The Sample Analysis at Mars (SAM) instrument suite on the Mars Science Laboratory (MSL) Curiosity rover got its first taste of solid Mars in the form of loose, unconsolidated materials (soil) acquired from an aeolian bedform designated Rocknest. Evolved gas analysis (EGA) revealed the presence of H2O as well as O-, C- and S-bearing phases in these samples. CheMin did not detect crystalline phases containing these gaseous species but did detect the presence of X-ray amorphous materials. In the absence of definitive mineralogical identification by CheMin, SAM EGA data can provide clues to the nature and/or mineralogy of volatile-bearing phases through examination of temperatures at which gases are evolved from solid samples. In addition, the isotopic composition of these gases, particularly when multiple sources contribute to a given EGA curve, may be used to identify possible formation scenarios and relationships between phases. Here we report C and S isotope ratios for CO2 and SO2 evolved from Rocknest soil samples as measured with SAM's quadrupole mass spectrometer (QMS).
    Keywords: Geophysics
    Type: JSC-CN-27880 , Lunar and Planetary Science Conference; Mar 18, 2013 - Mar 22, 2013; The Woodlands, TX; United States
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  • 8
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    Dehydration and Denitrification in the Arctic Polar Vortex During the 1995-1996 Winter (1998)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: Dehydration of more than 0.5 ppmv water was observed between 18 and 19 km (theta = 450-465 K) at the edge of the Arctic polar vortex on February 1, 1996. More than half the reactive nitrogen (NOy) had also been removed, with layers of enhanced NOy at lower altitudes. Back trajectory calculations show that air parcels sampled inside the vortex had experienced temperatures as low as 188 K within the previous 12 days, consistent with a small amount of dehydration. The depth of the dehydrated layer (approx. 1 km) and the fact that trajectories passed through the region of ice saturation in one day imply selective growth of a small fraction of particles to sizes large enough (〉10 micrometers) to be irreversibly removed on this timescale. Over 25% of the Arctic vortex in a 20-30 K range of theta is estimated to have been dehydrated in this event.
    Keywords: Geophysics
    Type: Paper-98GL00115 , Geophysical Research Letters (ISSN 0094-8534); 25; 4; 501-504
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  • 9
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    The Budget and Partitioning of Stratospheric Chlorine During the 1997 Arctic Summer (1999)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: Volume mixing ratio profiles of HCl, HOCl, ClNO3, CH3Cl, CFC-12, and CFC-11, CCl4, HCFC-22, and CFC-113 were measured simultaneously from 9 to 38 km by the Jet Propulsion Laboratory MkIV Fourier Transform Infrared solar absorption spectrometer during two balloon flights from Fairbanks, Alaska (64.8 N), on May 8 and July 8, 1997. The altitude variation of total organic chlorine (CCl(sub y)), total inorganic chlorine (Cl(sub y)), and the nearly constant value (3.7 +/- 0.2 ppbv) of their sum (Cl(sub TOT)) demonstrates that the stratospheric chlorine species available to react with O3 are supplied by the decomposition of organic chlorinated compounds whose abundances are well quantified. Measured profiles of HCl and ClNO3 agree well with profiles found by photochemical model (differences 〈 10% for altitudes below 35 km) constrained by various other constituents measured by MkIV. The production of HCl by ClO + OH plays a relatively small role in the partitioning of HCl and ClNO3 for the sampled air masses. However, better agreement with the measured profiles of HCl and ClNO3 is obtained when this source of HCl is included in the model. Both the measured and calculated [ClNO3]/[HCl] ratios exhibit the expected near linear variation with [O3](sup 2)/[CH4] over a broad range of altitudes. MkIV measurements of HCl, ClNO3, and CCl(sub y) agree well with ER-2 in situ observations of these quantities for directly comparable air masses. These results demonstrate good understanding of the budget of stratospheric chlorine and that the partitioning of inorganic chlorine is accurately described by photochemical models that employ JPL97 reaction rates and production of HCl from ClO + OH for the environmental conditions encountered: relatively warm temperatures, long periods of solar illumination, and relatively low aerosol surface areas.
    Keywords: Geophysics
    Type: Paper-1999JD900245 , Journal of Geophysical Research (ISSN 0148-0227); 104; D21; 26,653-26,665
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  • 10
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    A Comparison of Measurements from ATMOS and Instruments Aboard the ER-2 Aircraft: Tracers of Atmospheric Transport (1996)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: We compare volume mixing ratio profiles of N2O, O3, NO(y) H2O, CH4, and CO in the mid-latitude lower stratosphere measured by the ATMOS Fourier transform spectrometer on the ATLAS-3 Space Shuttle Mission with in situ measurements acquired from the NASA ER-2 aircraft during Nov 1994. ATMOS and ER-2 observations of [N2O] show good agreement, as do measured correlations of [O3], [NO(y)], [H2O], and [CH4] with [N2O]. Thus a consistent measure of the hydrogen (H2O, CH4) content of the lower stratosphere is provided by the two platforms. The similarity of [NO(y)] determined by detection of individual species by ATMOS and the total [NO(y)] measurement on the ER-2 provides strong corroboration for the accuracy of both techniques. A 25% discrepancy in lower stratospheric [CO] observed by ATMOS and the ER-2 remains unexplained. Otherwise, the agreement for measurements of long-lived tracers demonstrates the ability to combine ATMOS data with in situ observations for quantifying atmospheric transport.
    Keywords: Geophysics
    Type: Paper-96GL01677 , Geophysical Research Letters (ISSN 0094-8534); 23; 17; 2389-2392
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