Die Wertigkeit der Adenosintriphosphatase Reaktion zur Diagnostik von essentiellen Paraproteinämien

Zusammenfassung Bei 26 Fällen mit essentieller Paraproteinämie wurde die cytochemische Aktivität der Adenosintriphosphatase (ATPase) in den Plasmazellen des Knochenmarks untersucht. 15 Fälle zeigten eine erniedrigte und 11 Patienten eine normale ATPase-Aktivität. Die Untersuchungen zeigen, daß die Erniedrigung der ATPase für die Diagnostik des Plasmocytoms nicht spezifisch ist.Herrn Prof. Dr. W. Hoffmeister, Mannheim, zum 65. Geburtstag.     

Veränderte Aktivitäten der Enzyme des Energiestoffwechsels in Thrombocyten von Patienten mit Lebercirrhose und Splenomegalie

Zusammenfassung 1. Die Aktivitäten von 28 Enzymen aus verschiedenen Abschnitten des Energiestoffwechsels wurden in isolierten Thrombocyten von 17 gesunden Menschen und 15 Patienten mit gesicherter Lebercirrhose gemessen.2. Die für Gewebe bekannte Proportionskonstanz der Enzymaktivitäten des zentralen Segmentes der Glykolyse (TIM, GAPDH, PGK, GPM und EN) findet sich auch in den Thrombocyten als Ordnungsprinzip. Die mitochondrial lokalisierten Enzyme NAD-spezifische Isocitratdehydrogenase und Glycerophosphatoxydase wurden erstmalig in Thrombocyten mit relativ hoher Aktivität nachgewiesen.3. Die Plättchen von Patienten mit Lebercirrhose und Milzvergrößerung infolge portaler Hypertension zeigten signifikant erhöhte Enzymaktivitäten in allen untersuchten Stoffwechselwegen, insbesondere der mitochondrial lokalisierten Enzyme. Funktionell bedeutsam erscheinen der ausgeprägte Anstieg der Mg⁺⁺-aktivierbaren ATPase, die gleichbleibende Aktivität der Fructose-6-Phosphatkinase und eine Verminderung der Lactatdehydrogenase. Bei der Patientengruppe mit Cirrhose ohne Milzvergrößerung lagen fast alle gemessenen Aktivitäten der Thrombocyten im Normbereich.4. Es wird ein Patient mit Lebercirrhose ohne Milzvergrößerung beschrieben, dessen Thrombocyten um den Faktor 8 höhere Aktivitäten fast aller gemessenen Enzyme aufwiesen. Auch in diesen Plättchen zeigte die Lactatdehydrogenase eine Aktivitätsverminderung gegenüber der Norm.5. Ein Enzymdefekt der Plättchen wie bei Thrombasthenie wurde bei Lebercirrhose nicht gefunden. Nach unseren Kenntnissen über die Enzymausstattung von Blutzellen handelt es sich bei den Thrombocyten mit höherer Enzymaktivität um eine jugendliche Zellpopulation. Die Pathogenese wird besonders hinsichtlich der Rolle der vergrößerten Milz diskutiert.

---

Summary 1. The activities of 28 enzymes from different pathways of energy producing metabolism were measured in the isolated platelets of 17 normal persons and 15 patients with proven cirrhosis of the liver.2. In mammalian tissues a constant proportion between the enzymes of the central segment of the glycolytic pathway (TIM, GAPDH, PGK, GPM, EN) has been described. This constant proportion has been demonstrated also in the platelets. The mitochondrially localized enzymes NAD-specific Isocitratdehydrogenase and Glycerophosphatoxidase have been measured for the first time in platelets with a high activity.3. The platelets of patients with liver cirrhosis and splenomegaly following portal hypertension showed significant higher enzyme activities in all investigated pathways, mainly in the citric acid cycle. Functionally important could be the marked increase of the Mg⁺⁺ activated ATPase, the unaltered activity of the Phosphofructokinase and a lowered activity of the Lactatdehydrogenase in these platelets. The patients with cirrhosis but without a large spleen had normal enzyme activities of the platelets.4. One patient is described with cirrhosis without splenomegaly who had an elevation of nearly all measured enzymes by a factor 8 in his platelets. The LDH showed a decreased activity.5. No enzyme defect in the platelets of cirrhotic patients as in thrombasthenia was found. Basing on our knowledge of the enzyme equipment of blood cells the conclusion is drawn that the platelets with higher enzyme content represent a young cell population. The pathogenesis is discussed with special reference to the role of the enlarged spleen.

---

---

Teilergebnisse wurden vorgetragen auf dem 2. Symposium der European Association for the Study of the Liver, Göteborg, 1967 und der 24. Tagung der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten, Hamburg 1967.     

Localization of CEA,HCG, Lysozyme,alpha-1-antitrypsin,and alpha-1-antichymotrypsin in gastric cancer and prognosis

Summary Carcinoembryonic antigen (CEA),-human chorionic gonadotropin (HCG), alpha-1-antichymotrypsin (ACT), alpha-1-antitrypsin (AAT) and Lysozyme (LYS) were traced by immunoperoxidase staining in gastric carcinomas. The immunohistological results were evaluated in relation to histological types (WHO and Laurén), stage of disease, grade and survival time. CEA was demonstrated in 96% of the tumours, HCG in 34%, ACT in 78%, AAT in 42%, and LYS in 71%. Comparing the staining patterns of the antigens and the intensity of staining some differences were notable. Except for signet-ring cell carcinomas, all of which were intensively positive, CEA expression decreased significantly with loss of differentiation. This observation was not seen with the other marker substances. None of the tested markers was characteristic for one particular histological type, nor could they be correlated with the tumour stage or grade. The marker positivity of CEA, ACT and LYS was not related to survival time. For HCG only, a correlation between tissue expression and a restricted survival time was established. Patients with AAT positive carcinomas had a significantly better survival probability.     

Quantitative Evaluation of the Blood-Brain Barrier Capacity to Form Dopamine from Circulating L-DOPA

The ability of the blood-brain barrier to form dopamine from increasing doses of systemically administered L-DOPA has been studied in rats by a combination of chemical determination of dopamine, and histo-chemical and cytofluorometric measurements of L-DOPA and dopamine. The break-through of L-DOPA from the circulation into the brain parenchyma via the enzymatic blood-brain barrier was estimated by comparing the amount of newly formed dopamine in the caudate nucleus-putamen and in the cerebellum. The capillaries were found to efficiently trap L-DOPA in their walls, and an upper limit was reached (at an administered i.p. dose of 100 mg/kg of L-DOPA). It could be estimated that approximately 3 % of the total dose of L-DOPA given was decarboxylated by the blood-brain barrier. The possible influence by the regional differences in perfusion of the two regions seen after administration of L-DOPA was ruled out in measurements of local cerebral blood flow using the ¹⁴C-ethanol technique.     

Die Häufigkeit synchroner Entladungen motorischer Einheiten im M. erector trunci des gesunden Menschen

Zusammenfassung An vier gesunden jugendlichen Versuchspersonen wurde für den Multifidus-Anteil des M. erector trunci die Häufigkeit synchroner Entladungen zweier differenter Faseraktionspontentiale bei ein- (rechts-) und beidseitiger Ableitung untersucht. Die Beobachtungen genügten den Bedingungen für eine statistische Auswertung. Die Häufigkeit synchroner Impulse wurde durch die prozentuale Differenz der errechneten (= zufälligen) abzüglich der gezählten (= beobachteter) Koinzidenzen ausgedrückt. Die so erhaltenen Mittelwerte (Synchronisationsraten) lagen — in Entsprechung zu den von Buchthal für die Extremitätenmuskeln erhobenen Werten — sowohl für die einseitigen wie für die beidseitigen Ableitungen zweier differenter Aktionspotentiale unter ±10%. Ein signifikanter Unterschied der Synchronisationsrate bei den einzelnen Versuchspersonen fand sich nicht, ebenso keine Beziehung zwischen der Häufigkeit synchroner Entladungen und der mittleren Frequenz. Für die ausgewerteten Beobachtungen wurde die AS-Dauer bei leichter Halteaktivität bestimmt. In einzelnen Fällen konnte eine vollkommene Synchronisation zweier Motoneuronen-Entladungen und eine Abhängigkeit der Aktionspotentiale vom Atemcyclus beobachtet werden.Mit 6 TextabbildungenDie Untersuchungen wurden mit Unterstützung der Deutschen Forschungs-gemeinschaft durchgeführt.     

Development of behavioral audition in the kitten

The present study reports the maturation of behavioral responses to several classes of auditory stimulation and defines both natural and artificial stimuli to which kittens respond. This development is discussed relative to the physical maturation of the external auditory canal and the pinna and the extant electrophysiological and neuroanatomical literature. The external auditory canal did not reach its maximum depth until 12 ± 3 days of age and this was followed by a gradual deepening of the external concavity resulting in the complex adult pinna being formed at around 31 days of age. All but two of the animals showed diffuse pinna movements to tactile, visual and olfactory stimulation on the first post-natal day. The kittens showed a definite response to auditory stimuli by 5 ± 1.5 days. In all cases, the early responses consisted of a general arousal, bouts of pinna movements and facial squints. In general the earliest responses were seen to the tape recorded natural stimuli. Seventy-five percent of the animals responded to all stimulus presentations by 7 days of age, but showed adult latencies only at 14 days. Some degree of spatial localization appeared as early as 10 days, but 75% of the subjects showed this at 16 days with adult latencies coming in at 26 days. It was within this latter period that the animals began to show habituation to the non-animal sounds. These results demonstrate, by using a battery of both natural and artificial auditory stimuli, a diffuse reactivity in the neonatal kitten which suggests that the immature auditory system is quite capable of mediating simple behaviors before central connections are either electrophysiologically or anatomically mature.     

Nutzung von Gen5 und Gen6 ts-Mutanten des Phagen T3 für die Anzeige von Hemmstoffen der DNS-Synthese

In an enzyme-specific drug screening system nalidixic acid and 3'FTdR, inhibitors of DNA synthesis, both reduce the growth of wild type and temperature-sensitive point mutants of phage T3 with different efficiencies. The wild type shows the strongest sensitivity against the drugs, while an exonuclease mutant is the most insensitive variant. The DNA polymerase mutants exhibit an intermediate degree of inhibition. The anthracycline antibiotics violamycin BI and adriblastin which preferentially inhibit RNA synthesis show the same degree of inhibition for all mutants. This is true also for the RNA synthesis inhibitor lambdamycin, which is identical with chartreusin. The protein synthesis inhibitors chloramphenicol and o-phenanthroline, a chelating agent, impair all mutants to the same extent. Our data confirm the hypothesis that structural variants of essential viral enzymes, when compared with the wild type should sensitivities against specific inhibitors and show that this T3 system could be used for the indication of specific inhibitors of DNA synthesis.     

Estimation of dynamical model parameters taking into account undetectable marker values

Background  

Mathematical models are widely used for studying the dynamic of infectious agents such as hepatitis C virus (HCV). Most often, model parameters are estimated using standard least-square procedures for each individual. Hierarchical models have been proposed in such applications. However, another issue is the left-censoring (undetectable values) of plasma viral load due to the lack of sensitivity of assays used for quantification. A method is proposed to take into account left-censored values for estimating parameters of non linear mixed models and its impact is demonstrated through a simulation study and an actual clinical trial of anti-HCV drugs.