As a tool for screening large numbers of biological samples by means of amplification ͑e.g., Q or PCR͒ we have constructed a thermocycler that includes optionally a 96-channel or 960-channel glass fiber fluorimeter ͑combined with a cooled charge-coupled-device camera͒. We briefly describe the system integration of all components like liquid handling, thermostats, an x,y,z robot arm, and the glass fiber fluorimeter. The integrated glass fiber fluorimeter allows sensitive on-line measurements in 960 channels within 5 s. Two different screening procedures were carried out. In a first experiment PCR reactions were done in the presence of the known PCR inhibitor hematin and its suppressor transferrin. The system was used to titrate the suppressor with the inhibitor hematin in order to determine the maximum inhibitor concentration tolerated at a given suppressor concentration. We processed 96 PCR samples in parallel with 11 different concentration steps. In a second experiment the 960-channel glass fiber fluorimeter was used to monitor on line the amplification of the Q system in the presence or absence of an inhibitor ͑heparin͒. Since the doubling time of Q RNA variants is about 20 s, on-line detection is crucial for the experimental setup. The evolution of new RNA species adapted to high inhibitor concentrations could be proved by comparison of the fluorimetric signal and electrophoresis.
Modern microsystem application is concentrated on the development of microstructured sensors and actuators in integrated devices. Examples of that approach are microoptical components for endoscopic surgery, sensors and micropumps in integrated liquid analysers for pollution measurements.Often microsystems replace normal systems like commercially available piston pumps by silicon made liquid pumps in the hope of reducing costs but there is a lack of finding new applications.In contrast our approach of combining special developed microcompartments constructed with transparent membranes or microsieves and microdosing systems based on the ink jet principle together with optical devices like CCD cameras allow to overcome a real bottleneck in the new field of evolutionary biotechnology, the problem of screening a huge number of samples at a reasonable price.The goal of this approach is to design new molecules like enzymes by means of Darwinian evolution i.e. mutation and selection. In applying the selection principle to self amplifying entities like cell populations, viruses or self-replicating molecules under controlled selection pressures there is an absolute need to process large numbers of these entities in parallel. Preferentially this can be done in arrays of different microstructured compartments. The selection process is
Bei einer 72j ährigen Patientin traten nach dreimonatiger Procainamid-(Novocamid® )Behandlung in Tagesdosen von viermal 250 mg Gelenkschmerzen und serologische Veränderungen auf, die für ein Lupus-erythematodes-Syndrom sprachen. Nach Absetzen der Behandlung und Einleitung einer Corticosteroidtherapie in mäßiger Dosierung verschwanden die klinischen Symptome und die pathologischen Laboratoriumsbefunde bis auf einen auch weiterhin positiven Nachweis antinukleärer Faktoren. Die immunhistologische Untersuchung einer Nierenbiopsie zeigte glomeruläre Ablagerungen von yG-und 1M-Globulin und von Komplement, wie sie auch bei der Lupusnephritis gefunden werden können. Lichtoptisch waren keine glomerulonephritischen Veränderungen nachweisbar. Die Typisierung der antinukleären Faktoren ergab ebenfalls 1G-und yM-, aber keine 1A-Eigenschaf ten.Während Hydralazin, Diphenyihydantoin und Isoniazid als auslösende Faktoren eines Lupus-erythematodes-disseminatus-Syndroms geläufig sind (1), wurden seit der Erstbeschreibung durch Ladd 1962 (12) lediglich etwas über 30 Fälle mitgeteilt, die durch Procainamidmedikation induziert waren (5, 9, 13, 14). Diese relativ kleine Zahl überrascht bei der weiten Verbreitung des Medikamentes und dem häufigen Auftreten von zumindest monosymptomatischen Erythematodes-Manifestationen nach Gabe von Procainamid (7). Es soll daher ein weiterer Fall unter besonderer Berücksichtigung immunologischer Begleitphänomene mitgeteilt werden. Kasuistik Familienanamnese: Der Vater der am 4. 2. 1897 gebotenen Patientin A. R. (Hausfrau) war »Rheumatiker«, 74jährig an Arteriosklerose, die Mutter war im gleichen Alter an Tuberkulose gestorben. Eine elfjäh-
Plasma cyclic AMP was measured in different vessels in seventeen volunteers before and after stimulation with terbutaline. Differences between arterial blood and blood from the hepatic vein, right ventricle, inferior vena cava and a cubital vein could not be demonstrated. Only in the renal vein was the concentration of cyclic AMP decreased. Our results indicate that cyclic AMP is not generated from any specific isolated organ and that changes in cyclic AMP after subcutaneous injection of terbutaline reflect a general influence of this drug.
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