Local targeting of malignant gliomas by the diffusible peptidic vector 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid-substance p

PURPOSE: Malignant glial brain tumors consistently overexpress neurokinin type 1 receptors. In classic seed-based brachytherapy, one to several rigid (125)I seeds are inserted, mainly for the treatment of small low-grade gliomas. The complex geometry of rapidly proliferating high-grade gliomas requires a diffusible system targeting tumor-associated surface structures to saturate the tumor, including its margins. EXPERIMENTAL DESIGN: We developed a new targeting vector by conjugating the chelator 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid to Arg(1) of substance P, generating a radiopharmaceutical with a molecular weight of 1,806 Da and an IC(50) of 0.88 +/- 0.34 nmol/L. Cell biological studies were done with glioblastoma cell lines. neurokinin type-1 receptor (NK1R) autoradiography was done with 58 tumor biopsies. For labeling, (90)Y was mostly used. To reduce the "cross-fire effect" in critically located tumors, (177)Lut and (213)Bi were used instead. In a pilot study, we assessed feasibility, biodistribution, and early and long-term toxicity following i.t. injection of radiolabeled 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid substance P in 14 glioblastoma and six glioma patients of WHO grades 2 to 3. RESULTS: Autoradiography disclosed overexpression of NK1R in 55 of 58 gliomas of WHO grades 2 to 4. Internalization of the peptidic vector was found to be specific. Clinically, the radiopharmeutical was distributed according to tumor geometry. Only transient toxicity was seen as symptomatic radiogenic edema in one patient (observation period, 7-66 months). Disease stabilization and/or improved neurologic status was observed in 13 of 20 patients. Secondary resection disclosed widespread radiation necrosis with improved demarcation. CONCLUSIONS: Targeted radiotherapy using diffusible peptidic vectors represents an innovative strategy for local control of malignant gliomas, which will be further assessed as a neoadjuvant approach.

E- and P-selectin are not required for the development of experimental autoimmune encephalomyelitis in C57BL/6 and SJL mice

In multiple sclerosis and in its animal model experimental autoimmune encephalomyelitis (EAE), inflammatory cells migrate across the endothelial blood-brain barrier (BBB) and gain access to the CNS. It is well-established that alpha4 integrins are actively involved in leukocyte recruitment across the BBB during EAE. In contrast, the role of endothelial E- and P-selectin in this process has been a controversial issue. In this study, we demonstrate that P-selectin protein can be detected in meningeal blood vessel endothelial cells in healthy SJL and C57BL/6 mice and on rare parenchymal CNS blood vessels in C57BL/6, but not SJL, mice. During EAE, expression of P-selectin but not E-selectin was found up-regulated on inflamed CNS microvessels surrounded by inflammatory infiltrates irrespective of their meningeal or parenchymal localization with a more prominent immunostaining detected in C57BL/6 as compared with SJL mice. P-selectin immunostaining could be localized to CNS endothelial cells and to CD41-positive platelets adhering to the vessel wall. Despite the presence of P-selectin in wild-type mice, E/P-selectin-deficient SJL and C57BL/6 mice developed clinical EAE indistinguishable from wild-type mice. Absence of E- and P-selectin did neither influence the activation of myelin-specific T cells nor the composition of the cellular infiltrates in the CNS during EAE. Finally, endothelial-specific tetracycline-inducible expression of E-selectin at the BBB in transgenic C57BL/6 mice did not alter the development of EAE. Thus, E- and P-selectin are not required for leukocyte recruitment across the BBB and the development of EAE in C57BL/6 and in SJL mice.

Comparison of Fluid Types for Resuscitation in Acute Hemorrhagic Shock and Evaluation of Gastric Luminal and Transcutaneous P co 2 in Leghorn Chickens

The objective of this study was to compare the effects of 3 different fluid types for resuscitation after experimentally induced hemorrhagic shock in anesthetized chickens and to evaluate partial pressures of carbon dioxide measured in arterial blood (Paco2), with a transcutaneous monitor (TcPco2), with a gastric intraluminal monitor (GiPco2), and by end tidal measurements (Etco2) under stable conditions and after induced hemorrhagic shock. Hemorrhagic shock was induced in 40 white leghorn chickens by removing 50% of blood volume by phlebotomy under general anesthesia. Birds were divided into 4 groups: untreated (control group) and treated with intravenous hetastarch (haes group), with a hemoglobin-based oxygen carrier (hemospan group), or by autotransfusion (blood group). Respiratory rates, heart rates, and systolic arterial blood pressure (SAP) were compared at 8 time points (baseline [T0]; at the loss of 10% [T10%], 20% [T20%], 30% [T30%], 40% [T40%], and 50% [T50%] of blood volume; at the end of resuscitation [RES]; and at the end of anesthesia [END]). Packed cell volume (PCV) and blood hemoglobin content were compared at 6 time points (T0, T50%, RES, and 1, 3, and 7 days after induced hemorrhagic shock). Measurements of Paco2, TcPco2, GiPco2, and Etco2 were evaluated at 2 time points (T0 and T50%), and venous lactic acid concentrations were evaluated at 3 time points (T0, T50%, and END). No significant differences were found in mortality, respiratory rate, heart rate, PCV, or hemoglobin values among the 4 groups. Birds given fluid resuscitation had significantly higher SAPs after fluid administration than did birds in the control group. In all groups, PCV and hemoglobin concentrations began to rise by day 3 after phlebotomy, and baseline values were reached 7 days after blood removal. At T0, TcPco2 did not differ significantly from Paco2, but GiPco2 and Etco2 differed significantly from Paco2. After hemorrhagic shock, GiPco2 and TcPco2 differed significantly from Paco2. The TcPco2 or GiPco2 values did not differ significantly at any time point in birds that survived or died in any of the groups and across all groups. These results showed no difference in mortality in leghorn chickens treated with fluid resuscitation after hemorrhagic shock and that the PCV and hemoglobin concentrations increased by 3 days after acute hemorrhage with or without treatment. The different CO2 measurements document changes in CO2-values consistent with poor perfusion and may prove useful for serial evaluation of responses to shock and shock treatment.

Ändere dich, um dir treu zu bleiben (Interview von Martin Spiewak)

Der Beruf verlangt viel, die Kinder verlassen das Haus, die Eltern sterben. Die Psychologin Pasqualina Perrig-Chiello über eine besonders wechselhafte Lebensphase.

Measurement of negatively charged pion spectra in inelastic p+p interactions at plab = 20, 31, 40, 80 and 158 GeV/c

We present experimental results on inclusive spectra and mean multiplicities of negatively charged pions produced in inelastic p+p interactions at incident projectile momenta of 20, 31, 40, 80 and 158GeV/c (√s = 6.3, 7.7,8.8, 12.3 and 17.3GeV, respectively). The measurements were performed using the large acceptance NA61/SHINE hadron spectrometer at the CERN super proton synchrotron. Two-dimensional spectra are determined in terms of rapidity and transverse momentum. Their properties such as the width of rapidity distributions and the inverse slope parameter of transverse mass spectra are extracted and their collision energy dependences are presented. The results on inelastic p+p interactions are compared with the corresponding data on central Pb+Pb collisions measured by the NA49 experiment at the CERNSPS. The results presented in this paper are part of the NA61/SHINE ion program devoted to the study of the properties of the onset of deconfinement and search for the critical point of strongly interacting matter. They are required for interpretation of results on nucleus–nucleus and proton–nucleus collisions.

An die Mitglieder des Handwerker- und Gewerbe-Congresses: Frankfurt a. M., den 24. December 1848: P.P.: Durch beifolgende Ansprache an den deutschen Handwerker- und Gewerbstand und andere Beilagen erhalten Sie Kenntniß ...

Welsch (Projektbearbeiter): Aufruf an die Mitglieder des Deutschen Handwerker- und Gewerbe-Kongresses zum Eintritt in den neugegründeten 'Allgemeinen Deutschen Verein zum Schutze der Vaterländischen Arbeit'. Mit Zensurbalken

Na 1 Nachlass Max Horkheimer, 50 - Korrespondenzen u.a. an die Firma A. L. Stamm & Co (p. I 23, 190-421)

9 Briefe und Beilage zwischen Alfred Sohn-Rethel und Max Horkheimer, 1936-1940 sowie Briefwechsel mit Joan M. Levi; 6 Briefe zwischen Joan M. Levi und Max Horkheimer, 1940; 1 Brief von Max Horkheimer an Assistac Westcent, 25.06.1937; 1 Brief von John MacMurray an Walter Adams, 19.05.1937; 1 Brief von Walter Adams an Theodor W. Adorno, 01.06.1937; 2 Briefe zwischen Charles Somlo & Co und Max Horkheimer, 06.06.1939, 12.09.139; 1 Brief von Martin Sommerfeld an Max Horkheimer, 29.05.1934; 3 Briefe von Josef Sondek an Max Horkheimer, 1937, 1942; 3 Briefe zwischen Elsa Sontheimer, Max Sontheimer und Max Horkheimer, Februar 1940, 07.03.1940; 1 Drucksache von der The Southard School an Max Horkheimer; 1 Brief von der Soziologischen Verlagsanstalt an Gertrud Janosi, 20.07.1931; 9 Briefe zwsichen Maurice J. Speiser und Max Horkheimer, 1936-1948; 2 Briefe zwischen de Spengler und Max Horkheimer, 30.11.1936, 27.01.1937; 5 Briefe zwischen Sterling D. Spero und Max Horkheimer, 1936-1937; 1 Lebenslauf von Herbert Spielberg; 1 Brief und 2 Beilagen von René A. Spitz an Max Horkheimer, 23.06.1938; 2 Briefe von Elsa Spriesterbach an Max Horkheimer, Juli 1949; 1 Brief von Ida M. Stadie an Max Horkheimer, 21.05.1937; 20 Rechnungen von A. L. Stamm & Co an Max Horkheimer, 1938-1939; 1 Brief von Rose Horkheimer an A. L. Stamm und Co, 28.09.1938; 1 Betriebsanleitung und 1 Auslieferugnsschein für Max Horkheimer vom Standard Air Conditioning, 03.03.1936; 1 Brief von Max Horkheimer an Standard Air Conditioning, 28.03.1936; 5 Briefe zwischen Taylor Starck und Max Horkheimer, 1943; 8 Briefe zwischen Hans Staudinger und Max Horkheimer, 1937, 1943; 1 Briefauszug und Beilage von Paul Stefan, 1940 sowie Briefwechsel mit Samuel R. Wachtell; 1 Brief von Samuel R. Wachtell an Gertrude Blitz, 23.10.1940; 3 Briefe zwischen Leo Löwenthal und Samuel R. Wachtell, September 1940, 23.10.1940; 1 Brief von Loe Löwenthal an Hermann Kesten, 01.10.1940; 7 Briefe und Beilage zwischen George Stefansky und Max Horkheimer, 1939-1940; 2 Briefe zwischen dem Refugee Section of the American Friends Service Committee und Max Horkheimer, 16.05.1940, 28.05.1940; 3 Briefe zwischen dem Institute of International Education und Max Horkheimer, 09.04.1940, April 1940; 1 Brief von Max Horkheimer an Friess, 01.03.1940; 1 Brief vom Institute of Sociology Malvern und Max Horkheimer, 31.01.1940; 3 Briefe zwischen Stein und Max Horkheimer, 30.11.1934, 1936, 1937; 7 Briefe von Estell A. Stein an Max Horkheimer, 1929, 1937; 1 Brief von Franz Stein an Max Horkheimer; 1 Brief von Friedrich Pollock an Gertrude R. Stein, 22.03.1939; 1 Brief von Leo Stein an Max Horkheimer, 25.07.1944; 1 Brief von Max Horkheimer an Emilia Steinacher, 20.07.1937; 4 Briefe zwischen Friedrich Steinfeld und Max Horkheimer, 1941, 1945; 1 Brief und Beilage von Eugene G. Steinhof an Max Horkheimer; 3 Briefe zwischen Ernst Steinitz und Max Horkheimer, 25.04.1938, April 1938; 2 Briefe zwischen Theodor Steltzer und Eric E. Warburg, 07.03.1948; 4 Brief zwischen Hermine Sterler und Max Horkheimer, 11.09.1939, 1939, 1941; 4 Briefe zwischen Alfred K. Stern und Max Horkheimer, 1938, 1940 sowie 1 Brief und 1 Beilage von Max Gottschalk; 1 Brief von Max Gottschalk an Max Horkheimer; 2 Briefe und 1 Beilage zwischen Erich Stern und Max Horkheimer, 26.02.1937, 17.03.1937; 2 Briefe und Beilage von Eugene I. Stern an Max Horkheimer, 1938; 2 Briefe zwischen Joseph M. Weidberg und Max Horkheimer, 15.07.1938, 29.07.1938; 1 Brief von Max Horkheimer an das Cooperative Bureau for Teachers, 03.02.1938; 12 Briefe zwischen Günther Stern und Max Horkheimer, 1936, 1938 sowie Briefwechsel mit John Guggenheim Memorial Foundation; 3 Briefe und 1 Beilage zwischen der John Simon Guggenheim Memorial Foundation und Max Horkheimer, 1937; 1 Brief vom Social Research Quarterly an Max Horkheimer, 03.01.1937; 3 Briefe zwischen Hugo Stern und Max Horkheimer, 06.12.1937, Dezember 1937;