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  • American Society of Hematology  (88)
  • Wiley-Blackwell
  • 2000-2004  (82)
  • 1975-1979  (23)
  • 1965-1969  (3)
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  • 1
    Publication Date: 2004-11-16
    Description: The transcription factor PLZF is expressed in hematopoietic development and rearranged in t(11;17) acute promyelocytic leukemia (APL). PLZF expression is high in the quiescent progenitor CD34+ cell, and declines during differentiation along myeloid and erythroid lineages. PLZF encodes a BTB-Zinc finger transcriptional repressor that inhibits the cell cycle through inhibition of targets genes such as cyclin A and c-myc through the recruitment of histone deacetylase complexes. However, PLZF itself is regulated by acetylation. In a separate study we demonstrate that acetylation of PLZF by p300/CBP enhances the transcriptional repression activity of PLZF. Through a yeast two-hybrid study we found that PLZF associates with the protein deacetylase SIRT1. SIRT1 is a member of the sirtuin family of class III histone deacetylases. In model organisms such as yeast, worms and flies, sirtuins play a common role in lifespan extension. The interaction between PLZF and SIRT1 was confirmed by co-precipitation of endogenous proteins and localized to the zinc fingers of PLZF, the region targeted for acetylation by p300/CBP. Acetylation of PLZF mediated by p300/CBP was reversed by SIRT1. Furthermore while acetylation of PLZF enhances its ability to repress transcription, co-expression of SIRT1 decreased PLZF transcriptional repression activity, consistent with loss of acetylation. Conversely, inhibition of SIRT1 activity with nicotinamide enhanced both PLZF acetylation and transcriptional repression of PLZF on its endogenous target gene c-myc. Further, increasing PLZF acetylation by inhibition of SIRT1 was associated with decreased PLZF stability. Acetyl-PLZF levels were stabilized by inhibition of the proteosomal degradation machinery, together implying that PLZF acetylation and activation results in increased protein turnover. These data point to the increasing complexity of the role of acetylation in transcriptional regulation and stand in contrast with data for the related Bcl6 repressor where acetylation of the protein inhibits repression. These data also indicate a novel function for sirtuins in regulation of transcriptional repression.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2004-11-16
    Description: Multiple myeloma (MM) remains as an incurable disease although new therapies can achieve a high rate of complete remissions (CR). Unfortunately, most patients ultimately relapse due to the persistence of minimal residual disease (MRD), and only a minority could be cured. Detection and quantification of these cells is an important tool for monitoring these patients and predicting a potential relapse. Here we analyze by RQ-PCR the MRD in MM patients achieving CR in order to classify them into different risk categories. MATERIAL AND METHODS: 38 MM patients uniformly treated according to the GEM-2000 (Spanish group for Myeloma) protocol, and that have achieved CR following PBSCT were included in the study. 22 were IgG, 9 IgA, 6 B-J and 1 non-secretory (κ/λ 21/16). 27 were male & 11 female with a median age of 58 (range 48–65). Bone marrow samples obtained at diagnosis and 3 months after transplant were analyzed. Complete (VDJH) and incomplete (DJH) Ig rearrangements were amplified with the Biomed-2 strategy (Leukemia2003;17:2257). PCR clonal products were sequenced on an ABI Prism 377 Sequence detector. VH, DH and JH segments were identified by comparing with germinal sequences on V-Base and BLAST databases. An ASO primer at the N-region was designed for each patient with the OLIGO 6.0 software. RQ-PCR was then performed on an ABI Prism 7700 using the ASO specific forward primer, a JH reverse intronic primer (JH1–6) and a TaqMan probe (JH1,2,4,5, JH3 or JH6) to amplify the patient specific rearrangement. Sample quality and quantity was controlled evaluating the standard curve of the albumin gene amplification. MRD was calculated according to ΔCT method. RESULTS: In 14 out of the cases included in the study, MRD investigation was not possible because the N-region was not longer enough to design the ASO primer (n=3), poor quality in the diagnostic sample to obtain the standard curve (n=8) or low plasma cell infiltration at diagnosis to obtain correct dilutions (n=3). The remaining 24 patients were classified into different risk groups according to the MRD level obtained 3 months after transplantation with a cut-off point of 0.01% tumor cells. Thus, progression free survival (PFS) was longer in those patients with MRD〈 10−4 (p=0.03, figure 1A). By contrast, upon comparing the impact on PFS of immofixation (IFX) in these 24 patients that were in CR (defined by conventional electrophoresis criteria), it was observed that patients with IFX (−) didn’t showed a different outcome from those IFX (+) (figure 1B). CONCLUSION: In summary, although RQ-PCR is a labor and time-consuming technique, it is an useful tool for monitoring MRD in MM. The level of 10−4 can contribute to classify patients into 2 groups (high and low MRD) with different risk of relapse that can be used to design specific therapies.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 3
    Publication Date: 2004-11-16
    Description: Background. In the World Health Organization classification system (WHO), Splenic Marginal Zone B-cell Lymphoma (SMZBCL) is described as an indolent B-cell lymphoma, which generally presents as splenomegaly with involvement of the bone marrow and peripheral blood. The immunophenotype is usually IgM+, IgD+/−, cytoplasmic-Ig−/+, pan B antigens+, CD5−, CD10−, CD23−, CD43−/+ and cyclin D1−. A minority of cases (〈 20%) express CD5 antigen. The most frequent cytogenetic aberrations are deletions at 7q22–q32, gains of chromosome 3/3q and involvement of chromosomes 1 and 8. The objective of this study is the genetic characterization of SMZBCL by conventional cytogenetics and FISH. Patients and methods. We present 92 patients with SMZBCL from a multicenter study after being diagnosed morphologically and immunologically. Conventional cytogenetic studies were carried out on lymphoid cells from 72 hour-peripheral blood and/or spleen cultures stimulated with TPA. FISH was performed with centromeric probes from chromosome 3 and 12 and locus specific probes from P53 gene and 7q31 loci. Cross-species color banding FISH (RxFISH) probe was applied in 11 patients and SKY in 4 patients to redefine/confirm G-banding karyotype. Results. A clonal chromosome abnormality was found in 62/92 patients (67%) being identified in 37 (60%) as a complex karyotype. The most frequent recurrent abnormalities were deletions of 7q (30 cases) and gains of chromosome 3 (20 cases). 6/20 cases with gains #3, were gains of 3q arm, in three of them resulting from an unbalanced translocation. Thirteen cases showed rearrangements of 3q without gain of material. The chromosomes most frequently involved were: 7q, 3q, 14q, 8q and 1q (in more than 10 cases). Four cases presented gain of chromosome 3/3q and 7q deletion in the same karyotype. Four novel cytogenetic aberrations involving 14q32 were found in this series: t(6;14)(p12;q32) in two cases, t(14;19)(q32;q13) in two cases and t(10;14)(q24;q32), t(1;14)(q21;q32) and t(9;14)(pter-p22::14q32-14q11::9q22) in one case respectively. Conclusions. -In our series, the most frequent cytogenetic aberration in SMZBCL is a deletion at 7q (48%) and could be considered as a cytogenetic marker of these entity. -Gains of chromosome 3 or partial gains affecting only 3q arm are frequently observed in SMZBCL (32%) being chromosome 3 commonly rearranged. -RxFISH ans SKY techniques help us to define new aberrations not detected by conventional cytogenetics. -We describe translocations involving 14q32 that could help us to identify novel oncogenes related to SMZBCL.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 4
    ISSN: 0025-116X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Four fractions of poly(vinyl chloride) (PVC) having appreciably different tacticity distributions were prepared by selective extractions on samples polymerised at temperatures between +60 and -50°C. They were degraded thermally at 180°C in the solid state to conversions in the range 0,2 to 0,5% and in solution at 200°C to conversions in the range 1,6 to 5%. The polyene sequence distribution was investigated by ultra violet/visible (UV/VIS) and resonance Raman spectroscopy. The results show that the type of polyene sequence distribution depends markedly on the tacticity distribution of the polymer. Cross-linking reactions occur more readily as the syndiotacticity increases. The results are discussed and interpreted with reference to previous work relating degradation processes and tacticity.
    Additional Material: 6 Ill.
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  • 5
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Journal of High Resolution Chromatography 23 (2000), S. 373-378 
    ISSN: 0935-6304
    Keywords: Open tubular columns ; capillary electrochromatography ; column efficiency ; injected volume ; applied voltage ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The effect of some instrumental parameters on column efficiency in open tubular capillary electrochromatography (OTCEC) has been evaluated. First, it was investigated whether band broadening due to the sample injection process is within a tolerable range when an open tubular column (OTC) of about 10 μm i. d. is used. As a result of the small injection profile factor (K2 = 1.3), injected volumes must be sufficiently small (less than 10 pL) to avoid a significant efficiency loss (〉5%) when hydrodynamic injection by siphoning is employed. Secondly, the kinetic performance of OTCs in a CEC system was estimated from the variation of the reduced plate height (h) with the reduced linear velocity (ν) which was controlled by the voltage applied. Reasonable agreement was obtained between the theoretical h versus ν curve and the experimental values for a group of polycyclic aromatic hydrocarbons used as test compounds. Values of 0.25 for minimum h at an optimum ν of 16 are estimated, which permit separations with around 400,000 plates per meter to be obtained in less than 5 min. Finally, the possibility of estimating the diffusion coefficients of the solutes in the mobile phase from the plot of the height of a theoretical plate versus electroosmotic flow velocity is shown.
    Additional Material: 5 Ill.
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  • 6
    Electronic Resource
    Electronic Resource
    Weinheim [u.a.] : Wiley-Blackwell
    Materials and Corrosion/Werkstoffe und Korrosion 26 (1975), S. 703-706 
    ISSN: 0947-5117
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Autoclave arrangement for oxidation and corrosion tests of materials in pressurized waterThe authors describe an arrangement with an autoclave for corrosion and oxidation tests in pressurized water and steam. The autoclave has been conceived for a pressure of 250 bar at 500 °C. It is equipped with four locks enabling the specimens to be exchanged during operation without any markable influence on the working conditions. The aggressive medium can be exchanged continuously at a rate of 2,5 l/h. In addition to pressure and temperature controls the arrangement is equipped with a water quality control system.
    Notes: Es wird eine Autoklavenanlage für Korrosions-und Oxidationsuntersuchungen mit Hochdruckwasser bzw. Wasserdampf beschrieben. Die Auslegungsdaten des Autoklaven sind 250 bar bei 500 °C. Der Autoklav besitzt 4 Schleusen, über die während des Betriebes ein Probenwechsel ohne größeren Einfluß auf die Betriebsbedingungen möglich ist. Das korrodierende Medium kann kontinuierlich mit einer max. Rate von 2,5 l/h ausgetauscht werden. Neben der Druck- und Temperaturkontrolle ist eine Überwachung der Wasserqualität vorgesehen.
    Additional Material: 5 Ill.
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  • 7
    Electronic Resource
    Electronic Resource
    Weinheim [u.a.] : Wiley-Blackwell
    Materials and Corrosion/Werkstoffe und Korrosion 28 (1977), S. 676-683 
    ISSN: 0947-5117
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Phase transformations of the ZrNb 3 Sn 1 alloyThe phases transformations of cold-worked Zr-Nb 3-Sn 1-alloy have been studied as a function of heat tratements between 500-600°C in vacuum. Microscopic and X-ray diffraction analyses reveal allow us to state that again of a 50% cold-worked Zr-Bb 3-Sn 1-alloy at 597°C gives rise to a maximum ß-Nb content in the ß-Zr-matrix after 4 hours annealing.
    Notes: Die Phasenumwandlungen der Zr-Nb3-Sn 1-Legierung mit verschiedenen Kaltverformungen wurden in Abhängigkeit der Wärmebehandlung bei Temperaturen zwischen 500 und 600°C im Vakuum untersucht. Durch lichtmikroskopische Beobachtung und Röntgenbeugungsanalyse konnte im Fall einer Zr-Nb 3-Sn 10-Legierung mit 50%iger Kaltverformung, die einer Wärmebehandlung bei 597°C unterworfen wurde, nachgewiesen werden. Daß die ß-Nb-Konzentration in der ß-Zr-Matrix nach etwa 4 Stunden Wärmebehandlungszeit praktisch ein Maximum erreicht hat.
    Additional Material: 19 Ill.
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  • 8
    Electronic Resource
    Electronic Resource
    Weinheim [u.a.] : Wiley-Blackwell
    Materials and Corrosion/Werkstoffe und Korrosion 29 (1978), S. 258-265 
    ISSN: 0947-5117
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Influence of a mechanical treatment on the oxidation behaviour of ZrNb 3 Sn 1 alloy in oxygenIt has been found by means of gravimetric, microscopic, screen electron microscopic and x-ray diffraction investigations that the corrosion resistance of a Zr-Nb 3-Sn 1 alloy in oxygen (po2 = 3.3 × 104 Pa) between 400 and 460° C increases with increasing extent of cold rolling between 10 and 50%. Initially, the oxidation obeys a parabolic rate law with an activation energy the value of which becomes larger with increasing cold forming. After a critical thickness of the oxide layer is reached a transfer to a linear rate law occurs. The time of this transition becomes larger with increasing cold forming. Form the three processes which are responsible to the oxide layer growth mainly the diffusion of oxygen through the oxide layer via oxygen ion vacancies is the rate-determining step. In the later period of oxidation, however, a diffusion via grain boundaries must also be considered. The manner of the oxide growth is decisively determined by the cold forming regarding to a preferred orientation of the α-Zr grains in the alloy and to an epitaxial formation of oxide nucleus and of oxide crystals in the later period of oxidation.
    Notes: Mittels gravimetrischer, lichtmikroskopischer, rasterelektronenmikroskopischer und röntgendiffraktometrischer Untersuchungen wurde unmittelbar bestätigt, daß sich die Oxidationsbeständigkeit der Zr-Nb 3-Sn 1-Legierung im Sauerstoff (po2 = 3,33 × 104 Pa) bei Temperaturen zwischen 400 und 460 °C mit zunehmender Kaltverformung (zwischen 10 und 50% Kaltverformungsgrad) erhöht. Die Oxidation folgt zuerst einem parabolischen Zeitgesetz mit einer Aktivierungsenergie, deren Wert mit steigender Kaltverformung zunimmt. Nach Erreichen einer kritischen Schichtdicke wird ein Übergang zu einem linearen Zeitgesetz beobachtet. Die Übergangszeit ihrerseits nimmt mit steigender Kaltverformung zu. Obwohl während des Aufbaus des Zunders drei miteinander verknüpfte Vorgänge erfolgen, stellt die Diffusion von Sauerstoff durch die Oxidschicht über Sauerstoffionen-Leerstellen und längs von Kanten und Korngrenzen den reaktionsbestimmenden Schritt dar. Die Kaltverformung bestimmt die Art des Wachstums des Zirkonoxids, zunächst durch eine bevorzugte Orientierung der α-Zr-Körner in der Legierung und danach durch eine epitaktische Ausbildung der Oxidkeime und der Oxidkristallite im weiteren Verlauf der Oxidation.
    Additional Material: 7 Ill.
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  • 9
    ISSN: 1434-193X
    Keywords: Amino acids ; coupling ; N-Substituted amide ; Cyclizations ; Cyclic dipeptides ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: ---A short synthesis of new, functionalized seven-membered ring cyclic dipeptides is described. After the coupling of N-protected β-amino acids to N-substituted α-amino tert-butyl esters, the protective groups of the terminal functions were removed and the cyclization took place diastereoselectively in the presence of the coupling agent BOP. Amide substitution was found to be effective in promoting the cyclization of linear dipeptides.
    Additional Material: 1 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 2000 (2000), S. 807-811 
    ISSN: 1434-193X
    Keywords: Proline analogues ; Asymmetric synthesis ; Schöllkopf's method ; Silicon ; Amino acids ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: ---The asymmetric synthesis of a new proline surrogate, incorporating the dimethylsilyl group at position 4 of proline using Schöllkopf's bis-lactim ether method, is described.
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