Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura.

BACKGROUND Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of platelets on ultralarge von Willebrand factor multimers. This microvascular thrombosis causes multiorgan ischemia with potentially life-threatening complications. Daily plasma exchange and immunosuppressive therapies induce remission, but mortality and morbidity due to microthrombosis remain high. METHODS Caplacizumab, an anti-von Willebrand factor humanized single-variable-domain immunoglobulin (Nanobody), inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. In this phase 2, controlled study, we randomly assigned patients with acquired TTP to subcutaneous caplacizumab (10 mg daily) or placebo during plasma exchange and for 30 days afterward. The primary end point was the time to a response, defined as confirmed normalization of the platelet count. Major secondary end points included exacerbations and relapses. RESULTS Seventy-five patients underwent randomization (36 were assigned to receive caplacizumab, and 39 to receive placebo). The time to a response was significantly reduced with caplacizumab as compared with placebo (39% reduction in median time, P=0.005). Three patients in the caplacizumab group had an exacerbation, as compared with 11 patients in the placebo group. Eight patients in the caplacizumab group had a relapse in the first month after stopping the study drug, of whom 7 had ADAMTS13 activity that remained below 10%, suggesting unresolved autoimmune activity. Bleeding-related adverse events, most of which were mild to moderate in severity, were more common with caplacizumab than with placebo (54% of patients vs. 38%). The frequencies of other adverse events were similar in the two groups. Two patients in the placebo group died, as compared with none in the caplacizumab group. CONCLUSIONS Caplacizumab induced a faster resolution of the acute TTP episode than did placebo. The platelet-protective effect of caplacizumab was maintained during the treatment period. Caplacizumab was associated with an increased tendency toward bleeding, as compared with placebo. (Funded by Ablynx; ClinicalTrials.gov number, NCT01151423.).

Doxorubicin Affects Expression of Proteins of Neuronal Pathways in MCF-7 Breast Cancer Cells.

In the present article, we report on the semi-quantitative proteome analysis and related changes in protein expression of the MCF-7 breast cancer cell line following treatment with doxorubicin, using the precursor acquisition independent from ion count (PAcIFIC) mass spectrometry method. PAcIFIC represents a cost-effective and easy-to-use proteomics approach, enabling for deep proteome sequencing with minimal sample handling. The acquired proteomic data sets were searched for regulated Reactome pathways and Gene Ontology annotation terms using a new algorithm (SetRank). Using this approach, we identified pathways with significant changes (≤0.05), such as chromatin organization, DNA binding, embryo development, condensed chromosome, sequence-specific DNA binding, response to oxidative stress and response to toxin, as well as others. These sets of pathways are already well-described as being susceptible to chemotherapeutic drugs. Additionally, we found pathways related to neuron development, such as central nervous system neuron differentiation, neuron projection membrane and SNAP receptor activity. These later pathways might indicate biological mechanisms on the molecular level causing the known side-effect of doxorubicin chemotherapy, characterized as cognitive impairment, also called 'chemo brain'. Mass spectrometry data are available via ProteomeXchange with identifier PXD002998.

The Fatty Acid Biosynthesis Enzyme FabI Plays a Key Role in the Development of Liver-Stage Malarial Parasites

The fatty acid synthesis type II pathway has received considerable interest as a candidate therapeutic target in Plasmodium falciparum asexual blood-stage infections. This apicoplast-resident pathway, distinct from the mammalian type I process, includes FabI. Here, we report synthetic chemistry and transfection studies concluding that Plasmodium FabI is not the target of the antimalarial activity of triclosan, an inhibitor of bacterial FabI. Disruption of fabI in P. falciparum or the rodent parasite P. berghei does not impede blood-stage growth. In contrast, mosquito-derived, FabI-deficient P. berghei sporozoites are markedly less infective for mice and typically fail to complete liver-stage development in vitro. This defect is characterized by an inability to form intrahepatic merosomes that normally initiate blood-stage infections. These data illuminate key differences between liver- and blood-stage parasites in their requirements for host versus de novo synthesized fatty acids, and create new prospects for stage-specific antimalarial interventions.

Die Juden in der Bukowina

J. Marian

Na 1 Nachlass Max Horkheimer, 99 - Korrespondenzen u.a. mit Siegfried Kracauer und Alexander Mitscherlich (p. III 8, 213-408)

4 Briefe mit Antwort von Kohlhammer Verlag an Max Horkheimer, 1953, 1957; 12 Briefe mit Antwort und Beialge von Professor Hans Kohn an Max Horkheimer, 1953-1958; 3 Briefe mit Antwort von Professor Hans Kohn an Theodor W. Adorno, 1957-1958; 1 Brief mit Antwort von Professor Hans Kohn an Helmut Viebrock, 1958; 1 Brief von Theodor W. Adorno an Helmut Vriebrock, 1957; 2 Briefe mit 1 Antwort zwischen Rudolph Kolisch und Max Horkheimer, 1957; 1 Telegram von Professor Rudolph Kolisch an R. K., 1956; 1 Brief von Max Horkheiemr an den Kölner Universitäts-Verlag, 1957; 1 Drucksache von der Kölner Zeitschrift für Soziologie, 1953; 1 Drucksache von dem Kongress für Internationale Wissenschaftsgeschichte, 1951; 1 Brief mit Beilage von dem Königsteiner Kreis an Max Horkheimer, 1951; 1 Drucksache mit Beilage von der Zeitschrift "Konkret", 1958; 2 Briefe mit 1 Antwort zwischen Sekretärin Mathilde Koppen und Max Horkheimer, 1951, 1956; 2 Telegramme von Fritz Kortner an Max Horkheimer, 1952; 4 Briefe mit Antwort von Siegfried Kracauer an Max Horkheimer, 1951-1956; 1 Brief von Max Horkheimer an Professor Alexander Mitscherlich, 1956; 1 Brief mit Antwort von Hildegard Krämer an Max Horkheimer, 1956; 2 Briefe mit 1 Antwort von Dr. Rudolf Krämer-Badoni an Max Horkheimer, 1950, 1951; 2 Briefe mit Antwort von Professor Julius Kraft an Max Horkheimer, 1956, 1958; 1 Brief mit Antwort von Max Horkheimer an den Präsident d. LVA Heinrich Kraft, 1955; 2 Briefe mit Antwort von Werner Kraft an Max Horkheimer, 1953; 1 Brief von Angelo Kramer an Max Horkheimer, 1955; 2 Briefe von dem Architekt Ferdinand C. A. F. Kramer an Max Horkheimer, 1952; 2 Briefe mit Antwort von dem evangelischen Studentenpfarrer Dr. Rudolf Krapp an Max Horkheimer, 1958; 1 Brief mit Antwort und Beilage von dem Rechtsreferendar Heinz Kraus, 1956; 1 Drucksache von dem Frankfurter Studentenlied, 1956; 1 Aktennotiz von Professor Otto F. Kraushaar, 1953; 1 Brief von Max Horkheimer an den Regierungspräsident Wiesbaden,1952; 1 Aktennotiz von Klaus Kremer, 1958; 1 Brief von Dr. Stephanie Krenn an Max Horkheimer, 1952; 1 Aktennotiz von Dean Krasomil, 1952; 1 Brief mit Beilage von Anneliese Kreutz an Max Horkheimer, 1955; 1 Brief von Anneliese Kreutz an Professor Wilhelm Sturmfels, 1955; 1 Brief mit Antwort und Beilage von Robert H. Kreutzer an Max Horkheimer, 1954; 1 Brief mit Antwort von Professor Hans Hermann Kritzinger an Max Horkheimer, 1952; 2 Briefe mit Antwort von dem Betriebspsychologe Ludwig Kroeber-Keneth an Max Horkheimer, 1954; 1 Brief mit Antwort und Beilage von Professor Oswald Kroh an Max Horkheimer, 1952; 1 Todesanzeige von Professor Oswald Kroh, 1955; 1 Brief mit Antwort von Professor Wilhelm Kromphardt an Max Horkheimer, 1958; 1 Brief mit Antwort von Max Horkheimer an den Zirkus Krone, 1956; 1 Gutachten über Hans Joachim Krüger, 1958; 1 Brief mit Antwort von Melitta Krüger an Max Horkheimer, 1958; 2 Briefe mit Antwort und Beilage von dem Privatdozent Otto Kühne an Max Horkheimer, 1954, 1957; 1 Brief von Max Horkheimer an den Ministerialrat Dr. Dr. Kühn, 1953; 1 Vermählungsanzeige von Walter Kühn, 1957; 1 Aktennotiz von dem Rundfunk Dr. Kuhnert, ohne Jahr; 1 Brief von P. W. Krüger an Max Horkheimer, 1951; 1 Vermählungsanzeige mit Antwort von Hans K. Kullmer, 1953; 3 Briefe mit Antwort und Beilage von Dr. rer. pol. Ulrich Küntzel an Max Horkheimer, 1952; 1 Brief mit Antwort von dem Professor Fritz Baade an Max Horkheimer, 1952; 3 Breife mit Antwort von dem Verlag Walter de Gruyter an Max Horkheimer, 1954, 1955; 1 Brief mit Antwort von Max Horkheimer an den Kürschners Deutscher Gelehrten-Kalender, 1954; 2 Drucksachen von der Sektkellerei Kupferberg & Co, 1956; 3 Briefe mit Antwort von dem Reisebüro Kuoni an Max Horkheimer, 1957; 1 Brief mit Antwort von Max Horkheimer an das Kurhaus "Zur Rose" Bad Meinberg, 1956; 2 Briefe mit Antwort und Beilage von der Kurhessische Gesellschaft für Kunst und Wissenschaft an Max Horkheimer, 1954; 1 Gutachten von Thomas Gabor Kürthy, 1958; 1 Brief mit Antwort von Max Horkheimer an den Generaldirektor Dr. Kuss, 1953; 1 Brief mit Antwort von Professor Joseph J. Kwiat an Max Horkheimer, 1955;

Rede bei der Einweihung der Schloßkapelle in Wittelsbach am 27. September 1841

Stadtpfarrer Danhauser

Geistliche Rose : ein katholisches Gebet- und Andachtsbuch

hrsg. von Andreas Büschl

Herr! Du bist die Stütze meines Alters : ein vollständiges Gebetbuch für bejahrte katholische Christen

von J. Kremer

Are Intensive Family Preservation Services Useful?: A Study in the United Kingdom

This evaluation of the first year of an Intensive Family Preservation Service in England is based on the analysis of eighty-six families: fifty-seven families who received the service and a comparison group of twenty-nine families who did not. The study considered whether the program was fulfilling its objectives of reducing the number of children and young people in the public care system; offering a safe, supportive service for children who need protection; integrating the program into family support services as a whole, and improving family functioning. The findings were complex to interpret. Child protection was improved but there was not a reduction in the number of children needing out of home care (indeed there was an increase) meaning that short term savings in costs could not be made. Nor were there lasting improvements in the children’s behavior. There were instead a number of more subtle, arguably more sensitive outcomes: parents’ capacity to tolerate their child’s behavior was greater and overall family functioning was better for most families who received the service. Also families were, on the whole, able to make better use of follow up services.