Veränderungen von Spontanaktivität und Reizantwort retinaler und geniculärer Neurone der Katze bei fraktionierter Injektion von Pentobarbital-Na (Nembutal)

Zusammenfassung 1. Die Veränderungen der spontanen und Reaktionsaktivität von Neuronen des Tractus opticus und der Radiatio optica wurden bei fraktionierter Injektion von Pentobarbital-Na (Nembutal) untersucht. Dabei wurden in 5 min-Abständen jeweils 5 mg Nembutal injiziert und die mittlere Entladungsrate, das Intervall- und Poststimulushistogramm aufgenommen.2. Die Spontanaktivität der meisten retinalen Neurone zeigte bei Nembutaldosen zwischen 5 und 30 mg eine Zunahme der mittleren Entladungsrate, bei Experimenten mit geringer Spontantätigkeit bereits in der Kontrolle wurde von Anfang an eine Aktivitätsminderung beobachtet. Über 30 mg fällt die mittlere Entladungsrate bei allen Neuronen ab. Nach jeder Einzelinjektion kommt es zu einem mehrphasischen Verlauf der Entladungstätigkeit mit initialer Zunahme, sekundärer überschießender Verminderung und langsamer Erholung in einen steady state. Bei post-geniculären Neuronen fehlt die initiale Aktivitätssteigerung.3. Retinale Ganglienzellen zeigen bei niedrigen und mittleren Barbituratdosen charakteristische Veränderungen des Entladungsmusters mit gruppierten Entladungen und multimodalen Intervallverteilungen. Dabei sind die kürzesten Intervalle bei allen Neuronen mit 4–5 msec außerordentlich konstant und dosisunabhängig. Die längeren Intervalle (15–35 msec und Vielfache) sind variabler und dosisabhängig. Die beobachteten Vorzugsintervalle werden durch die supra- und subnormale Phase der Neurone nach dem Aktionspotential erklärt (delayed depolarization und polarizing afterpotential).4. Die Reaktion auf Lichtpunktreize im rezeptiven Feldzentrum zeigt eine stärkere Verminderung der späten tonischen als der initialen phasischen Reizantwort. Bei on-Zentrum-Neuronen tritt mit abnehmender steady-state-Aktivität eine off-Erregung in Erscheinung, die vor der Narkose zwar bereits vorhanden, aber nicht erkennbar war. Off-Zentrum-Neurone zeigen nur eine leichte Verminderung der off-Aktivierung. Die Reaktionen geniculärer Neurone wurden stärker vermindert als die von retinalen Neuronen.5. Die Bedeutung peripherer und allgemeiner neuronaler Faktoren für die Interpretation von Narkoseeffekten wird hervorgehoben.Die Arbeit wurde mit Unterstützung der Deutschen Forschungsgemeinschaft durchgeführt (Cr 30).     

Medikamentöse Therapie tachykarder Herzrhythmusstörungen

Zusammenfassung Tachykarde Herzrhythmusstörungen lassen sich im wesentlichen auf eine Störung der Erregungsbildung — Fokusgenese — oder der Erregungsleitung — begünstigend für eine Kreiserregung —, zurückführen. Antiarrhythmika wirken diesen beiden entscheidenden Störungen entgegen. Auf Grund ihrer Hauptwirkung auf das Aktionspotential isolierter Herzmuskelzellen in therapeutischen Dosen lassen sich die Antiarrhythmika in 4 Gruppen einteilen. Beim Menschen läßt die schwerpunktmäßige Beeinflussung der Erregungsleitung in den verschiedenen Anteilen des Erregungsleitungssystems Anwendungsschwerpunkte begründen und Nebenwirkungen voraussagen. Die Antiarrhythmikawirkung auf die elektrophysiologischen Vorgänge am kranken menschlichen Herzen sind bisher noch unzureichend untersucht, so daß für die klinische Therapie letztlich die Empirie, d.h. die systematische therapeutische Anwendung entscheidet. Für die wichtigsten Antiarrhythmika haben sich so bevorzugte Indikationen ergeben. Unter bestimmten Voraussetzungen ist in der Klinik aber auch eine <img src="/content/p3476h7766642357/xxlarge8222.gif" alt="ldquor" align="MIDDLE" BORDER="0">pathogenetisch differenzierende<img src="/content/p3476h7766642357/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0"> Therapie möglich, wenn auf Grund der bekannten spezifischen Wirkung eines Antiarrhythmikums ein Rückschluß auf die Pathogenese möglich wird; so u.a. beim Ansprechen auf Kalziumantagonisten, Typ Verapamil, die offenbar spezifisch auf sogenannte slow response Aktionspotentiale wirken. Vorbestehende TU-Abnormitäten im EKG weisen auf eine inhomogene Repolarisation als prädisponierenden Faktor für ventrikuläre Tachykardien durch Kreiserregung hin. Beim akuten Herzinfarkt kommt es zu wechselnden elektrophysiologischen Voraussetzungen für die Entstehung von Herzrhythmusstörungen, die eine therapeutische Beeinflussung durch ein einziges Antiarrhythmikum unwahrscheinlich erscheinen lassen. In der Hospitalphase ist eine ausreichend dosierte prophylaktische Gabe von Lidokain sinnvoll, in der prähospitalen Phase ohne Überwachungsmöglichkeit jedoch von zweifelhaftem Wert. Die prophylaktische Gabe von Betarezeptorenblockern kann in der posthospitalen Nachbehandlungsphase das Risiko des plötzlichen Herztodes um 50% senken. Auch bei anderen Risikopatienten mit ventrikulären Herzrhythmusstörungen ist eine konsequente antiarrhythmische Behandlung notwendig.</blockquote>     

Peripheral blood neutrophil production of interleukin-1 receptor antagonist and interleukin-1β

Journal of Clinical Immunology - The objective of this study was to characterize interleukin-1 receptor antagonist (IL-1ra) and interleukin-1β (IL-1β) production by human peripheral blood...     

Primary sequence and functional expression of a novel β subunit of the P-ATPase gene family

The cortical collecting tubule (CCT) of the mammalian kidney reabsorbs sodium and potassium, processes that are mediated by Na/K-ATPase and H/K-ATPase. CCT is also an important site for proton secretion, which is driven, in part, by H/K-ATPase. Na/K-ATPase and H/K-ATPase are members of the ion-motive P-ATPase gene family. They are closely related plasma membrane proteins which consist of <i><img src="/content/m831t1383v15m8k5/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> heterodimers. The urinary bladder of the toad <i>Bufo marinus</i> is the amphibian counterpart of mammalian CCT. We have previously characterized a ouabain-resistant Na/K-ATPase [see ref. 17], from TBM cells, a clonal cell line derived from the toad bladder, which expresses transepithelial sodium transport. In the present study, we report the primary sequence and functional expression of a novel <i><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> subunit (<i><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> <sub>bladder</sub>=<i><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> <sub>bl</sub>) isolated from a toad bladder epithelial cell cDNA library. The deduced polypeptide is 299 amino acids in length and has a predicted molecular mass of 33 kDa. The <i><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> <sub>bl</sub> protein exhibits 35% amino acid identity to the previously characterized <i><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> <sub>1</sub> of <i>B. marinus</i> Na/K-ATPase and 39% identity with <i><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> <sub>3</sub> of <i>B. marinus</i> Na/K-ATPase. It shares 38% identity with the mammalian <i><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> gastric H/K-ATPase and 52% with the mammalian <i><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> <sub>2</sub> Na/K-ATPase. Northern blot analysis shows that a 1.4×10<sup>3</sup>-base mRNA is expressed at a high level in bladder epithelial cells and eye and at a trace level in kidney; it is not detectable in significant amounts in the stomach, colon and small intestine. The <i><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> <sub>bl</sub> subunit can associate with the <i><img src="/content/m831t1383v15m8k5/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"></i> <sub>1</sub> subunit of <i>B. marinus</i> Na/K-ATPase to form a functional sodium pump in the <i>Xenopus laevis</i> oocyte. Our data indicate that, in addition to the known <i><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> <sub>1</sub> and <i><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> <sub>3</sub> isoforms, a third distinct isoform of the <i><img src="/content/m831t1383v15m8k5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"></i> subunit is present in the bladder epithelium. This new isoform could be functionally associated with <i><img src="/content/m831t1383v15m8k5/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"></i> subunits of either Na/K- or H/K-ATPase.     

Translocation (1;22)(p36;q11.2) with concurrent del(22)(q11.2) resulted in homozygous deletion of <Emphasis Type="Italic">SNF5/INI1</Emphasis> in a newly established cell line derived from extrarenal rhabdoid tumor

Malignant rhabdoid tumor (MRT) is a highly malignant pediatric cancer, which arises in various sites such as the kidney, brain, and soft tissues. Cytogenetic studies have revealed alterations of 22q11 in MRT. Recently, deletions and mutations of the &lt;i&gt;SNF5/INI1&lt;/i&gt; locus in 22q11.2 have been reported in MRT, suggesting that &lt;i&gt;SNF5/INI1&lt;/i&gt; is a tumor suppressor gene for MRT. Here we report our molecular cytogenetic study for a newly established cell line from extrarenal MRT with t(1;22)(p36;q11.2). Consequently, the reciprocal translocation was associated with the interstitial deletion of a small segment including &lt;i&gt;SNF5/INI1&lt;/i&gt;, and another, chromosome 22, showed terminal deletion, the breakpoint of which was located 70–80 kb centromeric to &lt;i&gt;SNF5/INI1&lt;/i&gt;, resulting in homozygous deletion of &lt;i&gt;SNF5/INI1&lt;/i&gt; in this cell line.     

Long-Term Follow-Up of the Changes in Circulating Cytokines, Soluble Cytokine Receptors, and White Blood Cell Subset Counts in Patients with Rheumatoid Arthritis (RA) After Monoclonal Anti-TNFα Antibody Therapy

To investigate the mechanism of the long-lasting efficacy of chimeric monoclonal anti-TNF&lt;img src="/content/kh2q2087t4mut036/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"&gt; antibody (cA2) therapy for rheumatoid arthritis (RA), eight patients with refractory RA were treated with a single infusion of cA2 and the changes in circulating cytokines (IL-1, IL-6, TNF&lt;img src="/content/kh2q2087t4mut036/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"&gt;, and IL-10), soluble cytokine receptors (TNF-RI, RII, and sIL-6R) and peripheral white blood cell (WBC) subset counts were followed up long-term (12 weeks) after cA2 therapy in them. Significant clinical responses (&gt;20% improvement according to Paulus' criteria) were observed just after cA2 infusion and lasted more than 4 weeks in all patients, as reported elsewhere. Moreover, five of the eight patients showed prolonged clinical responses (&gt;12 weeks). The elevated serum IL-6 and sTNF-RI (or RII) levels before treatment rapidly decreased after treatment. The serum IL-10 levels also significantly elevated before treatment. The elevations of serum IL-10 levels were augmented after treatment and stayed higher than the baseline in four patients with prolonged clinical responses. No significant TNF&lt;img src="/content/kh2q2087t4mut036/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"&gt;, IL-1&lt;img src="/content/kh2q2087t4mut036/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0"&gt; and -&lt;img src="/content/kh2q2087t4mut036/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"&gt;, or sIL-6R were detected in the sera of the patients before treatment and during the whole study period. On the other hand, peripheral lymphocytes as well as total WBC and neutrophils increased for 4 weeks after treatment. However, thereafter, only the lymphocyte count decreased gradually and stayed below the baseline long-term (12 weeks). FACS analysis revealed the predominance of T lymphocytes in the decrease in lymphocyte counts. These results suggest that the augmentation of IL-10 production and the decrease in T cells might partly contribute to the long-lasting efficacy of cA2 treatment in RA.     

Effects ofβ 2-adrenergic agonists on isolated guinea pig lung mast cells

The mast cell protective effects of the newly developed long-acting&lt;i&gt;&lt;img src="/content/x633l755hv724t70/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"&gt;&lt;/i&gt; &lt;sub&gt;2&lt;/sub&gt;-adrenergic salmeterol and formoterol were compared with those of conventionally used&lt;i&gt;&lt;img src="/content/x633l755hv724t70/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"&gt;&lt;/i&gt; &lt;sub&gt;2&lt;/sub&gt;-adrenergic, non-specific &lt;img src="/content/x633l755hv724t70/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"&gt;-agonists, disodium cromoglycate (DSCG) and theophylline. With the exception of DSCG, all the test agents inhibited ovalbumin-induced histamine release from enzymically dispersed guinea pig lung mast cells in a dose-dependent fashion. At the maximum concentration tested, theophylline produced the highest level of protection, inhibiting up to 90% of ovalbumin-induced histamine release whereas DSCG produced only 10% inhibition. The maximum inhibition produced by all the&lt;i&gt;&lt;img src="/content/x633l755hv724t70/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"&gt;&lt;/i&gt; &lt;sub&gt;2&lt;/sub&gt;-adrenergic tested was around 45%. While salmeterol was equipotent with salbutamol, formoterol was at least a 100-fold more potent. Hence the present study confirmed the previously reported mast cell stabilizing actions of conventional&lt;i&gt;&lt;img src="/content/x633l755hv724t70/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"&gt;&lt;/i&gt; &lt;sub&gt;2&lt;/sub&gt;-adrenergic and extended the observation to the newly developed long-acting analogues.     

Interaction of sensory and cognitive processes during visual recognition: The role of the associative areas of the cerebral cortex

The first part of the present study used a model of Alzheimer&lt;img src="/content/j743157634700t64/xxlarge8217.gif" alt="rsquo" align="BASELINE" BORDER="0"&gt;s disease in two groups of animals (three monkeys in each), given injections of neurotoxins (monkeys of group I) and physiological saline (monkeys of group II). Before injections, all monkeys were trained to discriminate stimuli containing different types of information (spatial frequency grids and geometrical figures of different colors and with different spatial relationships between objects) and to perform spatial selection. The dynamics of impairments in the characteristics of working memory were identified using delayed differentiation tasks in monkeys of both groups before injections and every two months after injections. Quantitative measures of impairments were made using the entropy of visual recognition, which characterizes uncertainty in decision-taking. The development of Alzheimer&lt;img src="/content/j743157634700t64/xxlarge8217.gif" alt="rsquo" align="BASELINE" BORDER="0"&gt;s disease in rhesus macaques was characterized by a deficit of working memory, resulting from lesions to the two component processes of memory. Impairments of the first of these in monkeys of group I were manifest as a significant increase in entropy, which is associated with correct decision-taking. The magnitude of the increase depended on the type of visual information. Impairments of the second component were characterized by increases in entropy associated with refusals to take decisions and were independent of the delay duration and the type of visual information. Monkeys given injections of physiological saline showed no significant changes in these characteristics. The features of working memory were also studied in the second part of the investigation, using four groups of Rhesus macaques: intact, those with bilateral extirpation of the sulcus principalis or field 7 or both: degradation again identified two components. Entropy associated with this was increased significantly for most of the stimuli tested on monkeys of all extirpation groups as compared with intact animals. Significant differences were found in these characteristics for a number of stimuli, which depended on the location of the structures removed. The characteristics of impairments of the components of working memory resulting in the development of Alzheimer&lt;img src="/content/j743157634700t64/xxlarge8217.gif" alt="rsquo" align="BASELINE" BORDER="0"&gt;s disease showed that the cholinergic mechanisms responsible for sensory processing differ from those involved in decision-taking. The structural-functional organization of the interaction of sensory and cognitive processes controlled by the motivation and attention systems is discussed, as is the role of the associative areas of the cortex.Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 89, No. 10, pp. 1226–1239, October, 2003.