992 resultados para Polyamine Analog N-1,n-11-diethylnorspermine
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Objective: NALP3-inflammasome is an innate mechanism, alternative to type-1 interferon, which is able to recognize nucleic acids and viruses in the cytoplasm and to induce pro-inflammatory response. Here, we hypothesized the involvement of inflammasome in the early defense against HIV-1 and in the full maturation of dendritic cells: for this, we evaluated the response of dendritic cells pulsed with HIV-1 in terms of inflammasome activation in healthy donors. Moreover, inflammasome response to HIV was evaluated in HIV-infected individuals. Design and methods: Monocyte-derived dendritic cells isolated from 20 healthy individuals (HC-DC) and 20 HIV-1-infected patients (HIV-DC) were pulsed with alditrithiol-2-inactivated HIV-1. We then analyzed inflammasome genes expression and interleukin-1 beta (IL-1 beta) secretion. Results: In HC-DC, HIV-1 induced higher NLRP3/NALP3 mRNA expression compared with other inflammasome genes such as NALP1/NLRP1 or IPAF/NLRC4 (P < 0.001). This augmented expression was accompanied by CASP1-increased and IL1B-increased mRNA levels and by a significant increment of IL-1b secretion (P < 0.05). Otherwise, HIV-1 failed to activate inflammasome and cytokine production in HIV-DC. HIV-DC showed an increased NLRP3/NALP3 basal expression, suggesting a chronic inflammatory profile of patients' immune cells. Conclusion: HIV-1 was able to induce a NALP3-inflammasome response in healthy individuals, indicating that this inflammasome could play a role in the first steps of HIV-1 infection; the consequent inflammatory process may be important for directing host immune response against the virus and/or disease progression. HIV-DC seemed to be chronically activated, but unresponsive against pathogens. Our findings could be of interest considering the ongoing research about dendritic cell manipulation and therapeutic strategies for AIDS involving dendritic cell-based immune-vaccines. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
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Background: Albuminuria has been considered a sine qua non condition for the diagnosis of diabetic nephropathy (DN) and has been widely used as a surrogate outcome of chronic kidney disease (CKD). However, recent data suggest that albuminuria may fail as a biomarker in a subset of patients, and the search for novel markers is intense. Methods: We analyzed the role of urinary RBP and of serum and urinary cytokines (TGF-beta, MCP-1 and VEGF) as predictors of the risk of dialysis. doubling of serum creatinine or death (primary outcome. PO) in 56 type 2 diabetic patients with macroalbuminuric DN. Results: Mean follow-up time was 30.7 +/- 10 months. Urinary RBP and MCP-1 were significantly higher in patients presenting the PO, whereas no difference was shown for TGF-beta or VEGF. In the Cox regression, urinary RBP. MCP-1 and VEGF were positively associated and serum VEGF was inversely related to the risk of the PO. However, after adjustments for creatinine clearance, proteinuria, and blood pressure only urinary RBP (OR 11.6; 95% CI 2.7-49.2, p = 0.001 for log RBP) and urinary MCP-1 (OR 11.0; 95% CI 1.6-76.4, p = 0.02 for log MCP-1) remained as significant independent predictors of the PO. Conclusion: Urinary RBP and MCP-1 are independently related to the risk of CKD progression in patients with macroalbuminuric DN. Whether these biomarkers have a role in the setting of normoalbuminuria and microalbuminuria in DN should be further investigated. (C) 2012 Elsevier Inc. All rights reserved.
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Recent studies have suggested that the scavenger receptor MARCO (macrophage receptor with collagenous structure) mediates activation of the immune response in bacterial infection of the central nervous system (CNS). The chemotactic G-protein-coupled receptor (GPCR) formyl-peptide-receptor like-1 (FPRL1) plays an essential role in the inflammatory responses of host defence mechanisms and neurodegenerative disorders such as Alzheimer's disease (AD). Expression of the antimicrobial peptide cathelicidin CRAMP/LL-37 is up-regulated in bacterial meningitis, but the mechanisms underlying CRAMP expression are far from clear.
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BACKGROUND: Highly active antiretroviral therapy (HAART) is being scaled up in developing countries. We compared baseline characteristics and outcomes during the first year of HAART between HIV-1-infected patients in low-income and high-income settings. METHODS: 18 HAART programmes in Africa, Asia, and South America (low-income settings) and 12 HIV cohort studies from Europe and North America (high-income settings) provided data for 4810 and 22,217, respectively, treatment-naive adult patients starting HAART. All patients from high-income settings and 2725 (57%) patients from low-income settings were actively followed-up and included in survival analyses. FINDINGS: Compared with high-income countries, patients starting HAART in low-income settings had lower CD4 cell counts (median 108 cells per muL vs 234 cells per muL), were more likely to be female (51%vs 25%), and more likely to start treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (70%vs 23%). At 6 months, the median number of CD4 cells gained (106 cells per muL vs 103 cells per muL) and the percentage of patients reaching HIV-1 RNA levels lower than 500 copies/mL (76%vs 77%) were similar. Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20,532 person-years). The adjusted hazard ratio (HR) of mortality comparing low-income with high-income settings fell from 4.3 (95% CI 1.6-11.8) during the first month to 1.5 (0.7-3.0) during months 7-12. The provision of treatment free of charge in low-income settings was associated with lower mortality (adjusted HR 0.23; 95% CI 0.08-0.61). INTERPRETATION: Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries. Timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART, might reduce this excess mortality.
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The antioxidant properties of tryptophan and some of its oxidative metabolites were examined by measuring how efficiently they inhibited peroxyl radical-mediated oxidation of phosphatidylcholine liposomes and B-phycoerythrin. Low micromolar concentrations of 5-hydroxytryptophan, 3-hydroxykynurenine, xanthurenic acid, or 3-hydroxyanthranilic acid, but not their corresponding nonhydroxylated metabolic precursors, scavenged peroxyl radicals with high efficiency. In particular, 3-hydroxykynurenine and 3-hydroxyanthranilic acid protected B-phycoerythrin from peroxyl radical-mediated oxidative damage more effectively than equimolar amounts of either ascorbate or Trolox (a water-soluble analog of vitamin E). Enzyme activities involved or related to oxidative tryptophan metabolism, as well as endogenous concentrations of tryptophan and its metabolites, were determined within tissues of mice suffering from acute viral pneumonia. Infection resulted in a 100-fold induction of pulmonary indoleamine 2,3-dioxygenase (EC 1.13.11.17) as reported [Yoshida, R., Urade, Y., Tokuda, M. ; Hayaishi, O. (1979) Proc. Natl. Acad. Sci. USA 76, 4084-4086]. This was accompanied by a 16- and 3-fold increase in the levels of lung kynurenine and 3-hydroxykynurenine, respectively. In contrast, endogenous concentrations of tryptophan and xanthurenic acid did not increase and 3-hydroxyanthranilic acid could not be detected. The activity of the superoxide anion (O2-.)-producing enzyme xanthine oxidase increased 3.5-fold during infection while that of the O2-.-removing superoxide dismutase decreased to 50% of control levels. These results plus the known requirement of indoleamine 2,3-dioxygenase for superoxide anion for catalytic activity suggest that viral pneumonia is accompanied by oxidative stress and that induction of indoleamine 2,3-dioxygenase may represent a local antioxidant defence against this and possibly other types of inflammatory diseases.
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BACKGROUND: Although combination antiretroviral therapy (cART) dramatically reduces rates of AIDS and death, a minority of patients experience clinical disease progression during treatment. OBJECTIVE: To investigate whether detection of CXCR4(X4)-specific strains or quantification of X4-specific HIV-1 load predict clinical outcome. METHODS: From the Swiss HIV Cohort Study, 96 participants who initiated cART yet subsequently progressed to AIDS or death were compared with 84 contemporaneous, treated nonprogressors. A sensitive heteroduplex tracking assay was developed to quantify plasma X4 and CCR5 variants and resolve HIV-1 load into coreceptor-specific components. Measurements were analyzed as cofactors of progression in multivariable Cox models adjusted for concurrent CD4 cell count and total viral load, applying inverse probability weights to adjust for sampling bias. RESULTS: Patients with X4 variants at baseline displayed reduced CD4 cell responses compared with those without X4 strains (40 versus 82 cells/microl; P = 0.012). The adjusted multivariable hazard ratio (HR) for clinical progression was 4.8 [95% confidence interval (CI) 2.3-10.0] for those demonstrating X4 strains at baseline. The X4-specific HIV-1 load was a similarly independent predictor, with HR values of 3.7 (95% CI, 1.2-11.3) and 5.9 (95% CI, 2.2-15.0) for baseline loads of 2.2-4.3 and > 4.3 log10 copies/ml, respectively, compared with < 2.2 log10 copies/ml. CONCLUSIONS: HIV-1 coreceptor usage and X4-specific viral loads strongly predicted disease progression during cART, independent of and in addition to CD4 cell count or total viral load. Detection and quantification of X4 strains promise to be clinically useful biomarkers to guide patient management and study HIV-1 pathogenesis.
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Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases.
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Welsch (Projektbearbeiter): 1. Thronrede (11. April 1847): Zugeständnis einer Versammlung nur der vereinigten Provinzial-Landtage (des Preußischen Vereinigten Landtages), der allerdings ausdrücklich keine dauernde Einrichtung sein soll. Ablehnung einer gesamtstaatlich-ständischen Versammlung sowie der Gewährung einer Verfassung unter Berufung auf das Volk. Die Aufgabe der Stände ist es nicht, "Meinungen zu repräsentiren", sie sind keine Volksrepräsentanten. - 2. Thronrede (2. April 1848; vorgetragen vom Ministerpräsidenten Camphausen): Bekenntnis zur deutschen Einheit und zu einer "wahre[n] constitutionelle[n] Verfassung". - 3. Thronrede (22. Mai 1848): Anerkennung der gewählten preußischen Nationalversammlung, Bekenntnis zur deutschen Einheit. - 4. Thronrede (26. Februar 1849): Mit der oktroyierten Verfassung vom 5. Dezember 1848 sind die Versprechungen vom März 1848 erfüllt. Aufruf an die beiden parlamentarischen Kammern und an die Regierung, sich zwecks Revision der Verfassung untereinander zu verständigen
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1. Friedrich Pollock: Verzeichnis der Änderungen in den Essays nach der Bearbeitung durch Alfred Schmidt, 4 Blatt; 2. Derselbe: Eigenhändige Korrekturnotiz zum Manuskript Schmidt, 1 Blatt; 3. Derselbe: Eigenhändige Notiz über Verteilung von Korrekturen, 1 Blatt; 4. Derselbe: Ergänzungen zu den Korrekturen vom 15. und 20.03.1968. a) 8 Blatt b) 8 Blatt; 5. Korrekturen, 2 Blatt; 6. Friedrich Pollock [?]: Verzeichnis der Essays von Max Horkheimer und der Korrekturen. a) 8 Blatt b) Teilstücke, 2 Blatt; 7. Derselbe [?]: Verzeichnis der Korrekturen, 3 Blatt; 8. Derselbe: Eigenhändige Gesprächsnotiz, 1 Blatt; 9. Derselbe: Eigenhändige Gesprächsnotiz, 1 Blatt; 10. Derselbe: "Sprachregeln", eigenhändige Notiz, 1 Blatt; 11. Derselbe: "Bedenkliche Stellen", eigenhändiges Verzeichnis, 1 Blatt; 12. Derselbe: "Vorschlag für den Inhalt von Max Horkheimers Essays I", eigenhändiges Verzeichnis, 1 Blatt; 13. Derselbe: Eigenhändige Gesprächsnotiz Friedrich Pollocks - Max Horkheimers über Pro und Contra, Neuveröffentlichung, 1 Blatt; 14. S. Fischer Verlaf: Schätzung des Umfangs der Essys, 1 Blatt; 15. Friedrich Pollock: Verzeichnis der Essays von Max Horkheimer, 3 Blatt; 16. Handschriftliches Verzeichnis der Aufsätze, Reden und Schriften Max Horkheimers, 4 Blatt; 17. "Max Horkheimer Essays" Verzeichnis, 1 Blatt; 18. Schönbach, Peter: 1 Brief mit Unterschrift an Max Horkheimer Frankfurt, 11.09.1964, 7 Blatt; 19. Liste der Anmerkungen Frau Dr. Adornos zu den Aufsätzen Prof. Horkheimers in der Zeitschrift für Sozialforschung, 2 Blatt; 20. Adorno, Gretel: 4 Briefe mit Unterschrift an Max Horkheimer, Korrekturvorschläge Frankfurt am Main 1962-1963, 5 Blatt; Vowort zur Neupublikation 1968 der Aufsätze aus der Zeitschrift für Sozialforschung (GS 3, S. 14-19); 1964-1968; Veröffentlicht in: Max Horkheimer "Kritische Theorie", Frankfurt am Main 1968, Seite IX- IXV; 1. Entwürfe Juli- September 1968; 2. Kalb, Peter E.: 1 Brief an Max Horkheimer und Beilage, Frankfurt am Main, 02.08.1968, 2 Blatt; 3. Klappentext der Buchausgabe, Korrekturfahne mit handschriftlichen Korrekturen; 4. Adorno, Theodor W.: 1 Brief mit Unterschrift an Max Horkheimer, Frankfurt, 17.07.1968, 1 Blatt; 5. Horkheimer, Max: "Der neuste Angriff auf die Metaphysik". Sonderdruck der Zeitschrift für Sozialforschung VI, 1937, mit eigenhändigen Korrekturen; 6. Derselbe: "Autoritärer Staat" Teilstücke aus der Gedenkschrift für Walter Benjamin, 1942. Als Typoskript vervielfältigt, 21 Blatt; 7. "Zitate aus 'Autoritärer Staat' heute", 4 Blatt; 8. Schmidt, Alfred: "Zur Idee der kritischen Theorie" = Nachwort zur Buchausgabe. Typoskript mit handschriftlichen Korrekturen von Max Horkheimer, 38 Blatt; 9. N.N.: Ergänzungsvorschläge zu dem Nachwort von Dr. Schmidt, 3 Blatt;
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"Fortune Polls on Antisemitism" (1947) (veröffentlicht unter dem Titel "Fortune Survey Analyzed by AJC Consultant to Appraise Results", in: News Letter, American Jewish Committee, Dezember 1947, S. 4):; 1. Max Horkheimer: Über Fortune Polls, a) Typoskript, 3 Blatt, b) Typoskript, 3 Blatt, c) Typoskript mit eigenhändigen Korrekturen, 3 Blatt, d) Typoskript, 3 Blatt; 2. Max Horkheimer: Über Fortune Polls und die Gefahren eines neuen Antisemitismus (Vortragsskript?), Typoskript und Manuskript, 4 Blatt; 3. Theodor W. Adorno (?): "Some Results of Adult Project". Typoskript mit eigenhändigen Korrekturen, 2 Blatt; 4. "Education Counteracts Prejudice" Auszug aus "Antisemitism among American Labor". Typoskript, 1 Blatt; 5. "Discord versus Harmony", Excerpt from: The Annals of the American Academy of Political and Social Science, March 1946, Typoskript, 1 Blatt; 6. Theodor W. Adorno: "Memorandum, Subject: Poll Controversy", 24.4.1948; 7. Leo Löwenthal: "Memorandum on Fortune Poll" und "Supplementary Memorandum on Fortune Poll", 8.10.1947. Typoskripte mit eigenhändigen Ergänzungen, 4 Blatt; 8. "Massing's Comment" (8.10.1947). Typoskript, 2 Blatt; 9. "Excerpts from Fortune Magazine 'The Fortune Survey': Racial and Religious Intolerance". Typoskript, 3 Blatt, a) "Summary of 'Fortune Survey' on Antisemitism in U.S. (Fortune, April, 1939)", Typoskript, 2 Blatt; 10. Leo Löwenthal: 1 Brief mit Unterschrift an Max Horkheimer, New York, 4.10.1947, 1 Blatt; 11. Exzerpt der Umfrage-Materialien der Opinion Research Corporation, Typoskripte, 61 Blatt; 12. Zahlenmaterial zu den Umfragen, 16 Blatt; Office of War Information, Bureau of Intelligence: Berichte über Antisemitismus: 13. "Attitudes toward Jews in the United States", 27.10.1942, a) als Typoskript vervielfältigt, 22 Blatt, b) Typoskript, 35 Blatt; 14. "Political Anti-Semitism: A Study of Indoctrination" (27.10.1942), a) als Typoskript vervielfältigt, 18 Blatt, b) Typoskript, 26 Blatt; 15. "Anti-Semitism - a Symptom of Disaffection" (8.10.1942), a) als Typoskript vervielfältigt, 8 Blatt, b) Typoskript, 12 Blatt; 16. Samuel H. Flowerman und Marie Jahoda: "Polls on Anti-Semitism. How much do they tell us?", Sonderdruck, 4 Blatt; 17. Fragebogen, Drucksachen, 4 Blatt; 18. Zeitungausschnitte aus: The Fortune Survey, 9 Blatt;
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"Beitrag des Instituts für Sozialforschung zu dem Forschungsprojekt über Autorität" (3.1.1951). Typoskript, 5 Blatt; "Reactions to the Antisemitic Incidents in January 1960. A Pilot Study in Frankfurt am Main. Summary of Procedure and Results" (1960). Typoskript, 6 Blatt (= Alt.Sig. IX 234.13 a); "Proposal for International Study of Anti-Semitism" (1960):; 1. American Jewish Committee: Luncheon Meeting, May 25, 1960, Typoskript, 2 Blatt; 2. American Jewish Committee, Institute of Human Relations: "The JDA Agencies and Germany" (17.5.1960). Als Typoskript vervielfältigt, 32 Blatt; Exzerpte aus Werken über Antisemitismus, Literaturlisten (etwa 1933-46):; 1. Everett R. Clinchy, Typoskript, 1 Blatt; 2. Paul K. Hatt, Typoskript, 3 Blatt; 3. John Moffat Mecklin, Typoskript, 3 Blatt; 4. Conrad Henry Moehlman, Typoskript, 4 Blatt; 5. Maurice Samuel, Typoskript, 5 Blatt; 6. Milton Steinberg, Typoskript, 2 Blatt; 7. "General Literature on Antisemitism", Liste, Typoskript mit handschriftlichen Ergänzungen, 1 Blatt; 8. "Bibliography" zum Judentum, 15 Blatt; 9. Literaturliste, handschriftliche Notizen, 9 Blatt; 10. Literaturliste, eigenhändige Notizen von Max Horkheimer, 1 Blatt; 11. Literaturliste, 1 Blatt; 12. Zitate zum Judentum aus Zeitschriften, 1 Blatt; Memorandum zum Antisemitismus (1944-48):; 1. S. Andhil Fineberg: "Notes on 'A Mask for Privilege' by Carey McWilliams", als Typoskript vervielfältigt, 4 Blatt; Carey McWilliams: "Memorandum" (8.5.1948), Typoskript, 3 Blatt; Lawrence Bloomgarden und S.A. Fineberg: "In Reply to Carey McWilliams Memorandum of May 8th", Typoskript, 3 Blatt; 2. Rundbriefe der American Jewish Sociological Society, 1944, als Typoskript vervielfältigt, 4 Blatt; 3. Bericht über einen Vortrag von Wladimir Eliasberg über Antisemitismus, Typoskript, 1 Blatt; Abschriften und Übersetzungen aus Zeitungsartikeln über Antisemitismus (1939-43):; 1. "A Note on Anti-Semitism", aus: The New Statesman and Nation (13.3.1939), Typoskript, 7 Blatt; 2. Abschriften aus deutschen und englischen Zeitungen, 1939, Typoskript, 1 Blatt; 3. "A Homility of the Bishop of Cremona" (Übersetzung aus: Osservatore Romano) 1939. Typoskript, 18 Blatt; Veröffentlichungen über Antisemitismus, Vorurteil, Demagogie (1941-63):; 1. Earl Raab und Seymour M. Lipset: "Prejudice and Society", Freedom Pamphlet Anti-Defamation League of B'nai B'rith (New York 1963), 48 Seiten; 2. Committee on Education, Training and Research in Race Relations of the University of Chicago: Bulletin, Nr. 1, 30.6.1948, 55. Seiten; 3. Solomon Andhil Fineberg: "Checkmate for Rabble-Rousers. What to Do When the Demagogue Comes to Town", Sonderdruck aus Commentary, Vol. 2, 1946 und eine Broschüre, 20 Seiten; 4. Kurt Lewin: "A new Approach to Old Problems", aus: Congress Week, 19.1.1945, 2 Blatt; 5. Eric A. Johnston: "Intolerance", New York, 11.1.1945, Heft, 8 Blatt; 6. Philip Wylie: "Memorandum on Anti-Semitism", aus: American Mercury, Januar 1945, 5 Blatt; 7. S.I. Hayakawa: "Race and Words", aus: Common Sense, Juli 1943, 3 Blatt; 8. David Riesman: "The Politics of Persecution". Als Typoskript vervielfältigt, 21 Blatt; 9. James P. Gifford, Frank D. Schroth, Maximilian Moss, Edward A. Richards, Samuel J. Levinson, Thomas G. Grace: "Anti-Semitism. It's Causes and Cures", New York, 1941, 30 Seiten;
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9. Horkheimer, Max: Memorandum für John Slawson: "German reeducation and suggestions for an investigation on the spot" Februar 1948; verschiedene Typoskripte, zum Teil mit handschriftlichen Korrekturen, circa 61 Blatt; drei Teilstücke, eins davon mit eigenhändigen Korrekturen, 6 Blatt; Manuskript, 1 Blatt; 10. Horkheimer, Max: Zur politischen Lage im Nachkriegsdeutschland und den Möglichkeiten des Instituts. Eigenhändige Notizen, 1 Blatt; 11. Eckert, Juliane: 1 eigenhändigen Brief mit Unterschrift an Bruno Manuel, Mannheim, 13.04.1947, 2 Blatt; 12. Auszug aus Sayers, Michael und Kahn, Albert E.: "The Plot Against the Peace". Typoskript, 1 Blatt; 13. Adressen-Notizen, 3 Blatt; 14. Materialien zu Fragen Nachkriegsdeutschlands, insbesondere zu den der Umerziehung. Drucksachen und Zeitungsausschnitte, nicht nummeriert. 1 Ordner;