"Clostridium difficile" has been recognized as the cause of a broad spectrum of enteric disease ranging from mild antibiotic-associated diarrhea to pseudomembranous colitis. This volume gives new insights into the microbiology, diagnostics and epidemiology of "Clostridium difficile" and describes recent strategies in treatment of diseases caused by this agent. Main parts of the volume are devoted to "Clostridium difficile" toxins A and B which are the major virulence factors. The molecular biology, biochemistry, pharmacology and cell biology of these toxins which are the prototypes of a new family of large clostridial cytotoxins is described in great detail. "Clostridium difficile" toxins act as glucosyltransferases to inactivate small GTP-binding proteins of the Rho family which are involved in regulation of the actin cytoskeleton, cell adhesion and various signaling processes.

Recent advances in molecular biology have shown GTPases and phosphoproteins to be the paramount molecular switches utilized intracellularly in biological systems. The origins of the GTPase switch appear to be almost as ancient as life itself, and through evolution nature has adapted this switch to a variety of purposes. In this two-volume work a broad survey of the major classes of GTPases is presented. The role of GTPases in ensuring accuracy during protein translation, a new look at the trimeric G-protein cycle, the molecular function of ARF in vesicle coating, the emerging role of the dynamin family in vesicle transfer, GTPases which activate GTPases during nascent protein translocation, and the many roles of ras-related proteins in growth, cytoskeletal polymerization, and vesicle transfer, are all described in 80 chapters by the leading authorities in their fields. Both detailed knowledge of specific systems or proteins and general principles of structure and function are offered. Much of this information has never been published before. At the rate the extended family of GTPases is growing it becomes increasingly unlikely that we will again get it to sit for a group portrait such as this. Therefore, the volume has the chance to become "the" reference work for GTPases.

In recent years remarkable progress has been accomplished with respect to our knowledge about bacterial protein toxins. This refers especially to structural aspects of protein toxins but also holds true for genetics, molecular biology and biochemical mechanisms underlying the action of toxins. This volume covers the very current and exciting aspects of up-to-date bacterial toxicology and comprehensively reviews the most important bacterial protein toxins such as the intracellular acting toxins which exhibit enzyme activity, as well as those toxins that interact with cell plasma membranes by damaging the membranes (pore formation) or stimulating cell receptors (superantigens). This is the most current reference work on these important bacterial protein toxins, which are presented from the point of view of different disciplines such as pharmacology, microbiology, cell biology and protein chemistry.

"Clostridium difficile" has been recognized as the cause of a broad spectrum of enteric disease ranging from mild antibiotic-associated diarrhea to pseudomembranous colitis. This volume gives new insights into the microbiology, diagnostics and epidemiology of "Clostridium difficile" and describes recent strategies in treatment of diseases caused by this agent. Main parts of the volume are devoted to "Clostridium difficile" toxins A and B which are the major virulence factors. The molecular biology, biochemistry, pharmacology and cell biology of these toxins which are the prototypes of a new family of large clostridial cytotoxins is described in great detail. "Clostridium difficile" toxins act as glucosyltransferases to inactivate small GTP-binding proteins of the Rho family which are involved in regulation of the actin cytoskeleton, cell adhesion and various signaling processes.

In recent years remarkable progress has been accomplished with respect to our knowledge about bacterial protein toxins. This refers especially to structural aspects of protein toxins but also holds true for genetics, molecular biology and biochemical mechanisms underlying the action of toxins. This volume covers the very current and exciting aspects of up-to-date bacterial toxicology and comprehensively reviews the most important bacterial protein toxins such as the intracellular acting toxins which exhibit enzyme activity, as well as those toxins that interact with cell plasma membranes by damaging the membranes (pore formation) or stimulating cell receptors (superantigens). This is the most current reference work on these important bacterial protein toxins, which are presented from the point of view of different disciplines such as pharmacology, microbiology, cell biology and protein chemistry.

Die Aufgaben des niedergelassenen Nervenarztes fUr die psychiatrische Forschung Wichtige psychiatrische Forschungsfragen, von denen einige im folgenden erlautert werden, konnen heute nur in Zusammen- arbeit zwischen niedergelassenen Nervenarzten und Psychiatri- schen Universitatskliniken bzw. wissenschaftlichen Institutionen gelost werden. Ein besonders wichtiges Forschungsgebiet fUr diese Zusammen- Therapieforschung. Die langjahrigen Verschrei- arbeit ist die bungsgewohnheiten der Nervenarzte in der Praxis konnen das Fundament fur die endgiiltige Wirkbeschreibung neuer Prapara- te sein. Ein neuentwickeltes Antidepressivum, das auf Grund theoretischer Vorstellungen uber den gestOrten Transmitterstoff- wechsel bei der Depression in den Laboratorien der pharmazeu- tischen Industrie entwickelt worden ist, mul3 sich erst im Alltag des Nervenarztes bewahren. Durch haufige Verschreibungen kann er Vor-und Nachteile im Wirksamkeitsspektrum und feh- lende oder vermehrte unerwiinschte Wirkungen mit langbewahr- ten Antidepressiva vergleichen. Ein so\ches Urteil wird auf den Vergleich einer sehr grol3en Zahl von Verordnungen beruhen und kann damit letztlich dem Urteil klinischer Priifungen in Universi- tatskliniken, die sich oft nur auf 10-30 Patienten beziehen, uber- legen sein. Allerdings benotigt diese Meinungsbildung durch den Nervenarzt in der Praxis Zeit. Wir haben am Beispiel der langjah- rigen Verordnung von Sulpirid nicht nur als Neuroleptikum, son- dem auch als Antidepressivum auf die wichtige Aufgabe des nie- dergelassenen Nervenarztes fUr die Therapieforschung hingewie- sen (Benkert u. Hoisboer 1984). Dieser Prozel3 der langfristigen Beobachtung des Wirksamkeitsspektrums eines Psychopharma- kons in der Praxis mul3 schliel3lich neben anderen Evaluations- methoden (Moller u. Benkert 1980) als eine bedeutsame naturali- stische Methode der Evaluationsforschung in der psychiatrischen Pharmakotherapie angesehen werden.