Das herzmuskeleigene Acetylcholin

Zusammenfassung Mit der in einer vorangegangenen Mitteilung angegebenen Methodik wurde der Gesamtgehalt der Herzmuskulatur an gebundenem Acetylcholin in /g Frischgewicht (ausgedrückt in Acetylcholinchloridäquivalenten) bestimmt.An 141 Froschherzen und 59 Rattenherzen fanden sich folgende Werte:Die Vorhofsmuskulatur von Rana temporaria enthält im Herbst 0,45 (± 0,158), im Frühwinter 1,40 (± 0,58) /g. Die Kammermuskulatur der gleichen Art enthält für Frühjahr, Sommer und Herbst im Mittel 0,34 (± 0,10) /g, ab Oktober steigen die Werte, wir fanden von Oktober bis Dezember 0,59 (± 0,25) /g. Die Werte von Herzbasis und Herzspitze von Rana temporaria zeigen eine große Streuung und keine signifikanten Unterschiede. Die Ventrikelmuskulatur von R. esculenta ergab im Durchschnitt von 30 Versuchen (Juli—Oktober) 0,62 (± 0,29) /g. Die Oktoberwerte sind gegenüber den Sommer- und Herbstwerten etwas erhöht. Im Gesamtdurchschnitt hat die Herzkammer von R. esculenta etwas mehr ACh als diejenige von R. temporaria.Die Vorhofsmuskulatur der Ratte zeigt mit 2,28 (± 0,547) /g Frischgewicht einen recht hohen ACh-Gehalt. Der Rattenventrikel besitzt rechts mehr ACh als links, der Wert der Muskulatur des rechten Ventrikels beträgt 1,30 (± 0,22) /g, derjenige des linken Ventrikels 0,73 (± 0,148) /g.     

A comparative immunohistological study of cerebellar enolases

Summary A comparative immunohistological study of the neurone-specific enolase and enolase, demonstrates the exclusive neuronal localization of enolase and its absence from glial cells. In contrast, enolase is located in astroglial cells. The validity of enolase as a neuronal marker and enolase as an astrocytic marker, is confirmed both by a double labelling technique, using antibodies to and to revealed with fluorescence or peroxidase in the same tissue sections, and by immunoelectronmicroscopy.     

Adjuvant-induced inflammatory disease in the rat: Plasma levels of peptide hydrolases and protease inhibitors reflect disease activity

Both during the primary (localized) inflammation and the development of the secondary (generalized) inflammation in adjuvant-treated rats, the plasma level of functional -macroglobulins increases while proteases (measured as peptide hydrolases) sharply decrease. The decreased peptide hydrolase levels during episodes when protease spillage into the bloodstream is elevated, suggests a more rapid clearance of -macroglobulin-protease complexes associated with inflammation.     

Increased levels of α6 integrins are associated with the metastatic phenotype of human breast cancer cells

Integrins play an important role in interactions between cells and the extracellular matrix, and thus have a potential role in metastasis. Expression levels of 6, 1 and 4 integrin sub-units were measured in a panel of human breast cancer cell lines by RT/PCR, immunoprecipitation and flow cytometry. All the lines expressed 6, with the highest levels in the MDA-MB-231 and MDA-MB-435 cells. These grew the most aggressively and were metastastic in nude mice. Low levels of 6 protein were measured in breast cancer cells that were poorly tumorigenic and non-metastatic in nude mice, and there was an inverse relationship between ER and 6 expression. RT/PCR revealed that all lines expressed the 2 isoforms of 6, with the 6A isoform generally more abundant than 6B isoform. Clones of MDA-MB-435 were isolated by sterile sorting for cells with high or low 6 expression, and two variants established from metastases in nude mice were found to differ in 6 expression. When injected into nude mice, the 6-high variants produced significantly more lung metastases than the 6-low variants. 1 was abundant in all lines, while 4 was not detected in MDA-MB-134 cells, and in the MDA-MB-435 cells an alternately spliced variant of 4 was identified. Sequencing of the alternate variant revealed a novel sequence from a splicing event in the cytoplasmic tail of 4. None of the cells with this variant mRNA expressed detectable levels of 4 protein. Our results suggest that high 6 expression in human breast cancer cells is associated with tumorigenicity and metastatic potential.     

Recommendations for the standardization of lead positions in surface electromyography

Summary Standardized lead positions for recording myoelectric signals are given for various muscles. The positions are given in terms of (1) the lead line connecting two anatomical landmarks and (2) the central lead point about which the electrodes are placed symmetrically on the lead line.This research was financially supported by the Sonderforschungsbereich 152 of the Deutsche Forschungsgemeinschaft     

SpecialEscherichia coli serotypes among enterotoxigenic strains from diarrhoea in adults and children

106 enterotoxigenicEscherichia coli strains from children and adults from many parts of the world were serotyped for O and H antigens. Some OH types,i.e. O6H16, O8H9, O15H11, O25H42, O78H11 and O78H12, were found repeatedly from different geographical locations. Some of these OH serotypes were only found rarely among more than 20000E. coli strains collected over many years from different locations and sources. It is suggested that these special OH serotypes represent clones which have been selected to the special conditions in the small intestine and selected to carry the plasmids necessary to provoke diarrhoea.     

Analysis of γδ+ T cells in peripheral blood of children with perinatal human immunodeficiency virus (HIV) infection

The present study examined CD8 antigen expression and variable (V) gene segment usage by T cell receptor (TCR)-⁺ lymphocytes in peripheral blood of symptomatic children with perinatal HIV infection. The relative number of ⁺, CD8⁺ T cells in most of the infected children was higher than that in uninfected children from HIV⁺ or HIV^– mothers and correlated with the immunodeficiency status of the patients. Infected infants and children over 1 year old also showed an increased proportion of V1-J1⁺ T lymphocytes. CD8 expression on those cells was higher in infected than in uninfected infants and children. Sequence analysis of the gene rearrangement of the predominant V1 family in peripheral blood of three HIV⁺ donors revealed extensive junctional diversity. These results suggest that the V skewing in the majority of HIV⁺ children reflects peripheral expansion of V1-J1⁺ T lymphocytes early in life, which might be involved in the mechanisms of HIV-induced immunodeficiency.     

Induction of β-family chemokines mRNA in human embryonic astrocytes by inflammatory cytokines

The cellular infiltration found during CNS inflammation consists of monocytes and activated T cells, suggesting the presence of cell-specific chemotactic signals during inflammatory responses. Astrocyte chemokine expression might contribute to site-specific leukocyte infiltration within the CNS. To investigate the factors that regulate astrocyte chemokine expression, we examined the ability of human fetal astrocytes to induce -family chemokine mRNA. Astrocyte-derived monocyte chemoattractant protein-1 (MCP-1), RANTES, macrophage inflammatory protein-1 (MIP-1), and MIP-1 mRNA were easily induced by lipopolysaccharide and/or the proinflammatory cytokines (IFN and/or TNF-), respectively. Addition of both IFN and TNF- together did not lead to an additive effect but resulted in the inhibition of MCP-1 and MIP-1 mRNA expression, indicating that interaction between chemokines and cytokines may play a key role in regulating the local immune response of resident and infiltrating cells at the site of lesion. Interestingly, ultraviolet light-inactivated measles virus, but not cytomegalovirus, strongly induced expression of MCP-1, RANTES, MIP-1, and MIP-1 mRNA in human embryonic astrocytes, especially MCP-1 and MIP-1. An association occurs between the -family chemokine expression in astrocytes and inflammatory factors/virus, suggesting a possible role for -family chemokines in the pathogenesis of CNS inflammatory disease.     

Prostacyclin acts in rat gastric (fundic) mucosa via the intracellular ‘second messenger system’

Using a specific radioimmunoassay technique it seems that Prostacyclin (PG-I₂) has a strong effect on the cyclic nucleotide content of the rat gastric (fundic) mucosa. 1 min after an intragastric application of 100 g/kg PG-I₂ the cAMP-content and in the 5th min the cGMP-content showed a highly significant decrease. It seems that the basic mechanism of action of PG-I₂ is a typical hit and run effect, acting on the intracellular second messenger system.     

3′-Deoxy-3′-fluoroinosine as a potent antileishmanial agent

We studied the antileishmanial activity of 3-deoxy-3-fluoroinosine (3-FI) againstLeishmania tropica andL. donovani. In in vitro cultivation, the EC₅₀ values (the concentration of drug necessary to inhibit the growth rate of cells to 50% of the control value) obtained for 3-FI against the promastigotes ofL. tropica andL. donovani were 2.3×10^–7 and 1.0×10^–6 M, respectively. It was less toxic toward mouse mammary-tumor FM3A cells, a model host; the EC₅₀ value was 1.9×10^–4 M. Leishmania promastigote metabolized 3-FI to 3-deoxy-3-fluoroadenosine 5-triphosphate (3-FATP) but FM3A cells did not. 3-FI was effective againstL. donovani amastigotes in J774.1 cells in an in vitro cultivation system under conditions similar to those used in the in vivo assay. 3-FI (50 mg/kg, given i.v.)showed a cytotoxic effect against the amastigotes ofL. donovani in mice.     

Antiandrogentherapie der pathologisch gesteigerten und abartigen Sexualität des Mannes

Zusammenfassung Mit 100 mg Cyproteronacetat (1.2-Methylen-6-chlor-^4,6-pregnadien-17-ol-3.20-dion-17-acetat) pro Tag per os konnten innerhalb von 10–14 Tagen Libido und Potenz hypersexuell bzw. abartig sexuell erregter Männer unabhängig vom Lebensalter in bisher 17 behandelten Fällen ohne Therapieversager und ohne wesentliche Nebenwirkungen gehemmt werden.

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Summary With 100 mg Cyproteroneacetate (1.2-methylene-6-chloro-^4,6-pregnadiene-17-ole-3.20-dione-17-acetate) orally applied per day libido and potency of men suffering from hyper- or abnormal sexuality were inhibited within 10 to 14 days independent from the age of the patients in 17 cases up to this time without any failure in therapy and without fundamental side effects.

     

Processing of binaural stimuli by cat superior olivary complex neurons

Summary A method was developed to record stereotactically from the cat Superior Olivary Complex (SOC) using glass micropipettes. Sound stimulation was given through a closed system that permitted independent variation of interaural time (time) and intensity (int) differences. The most common binaural units found (n = 34) were ipsilateral excitatory, contralateral inhibitory (EI¹), cells of the Lateral Superior Olive (LSO). Some Medial Superior Olive (MSO) cells and presumed MSO ascending afferents were found but, as noted by other authors, we found it difficult to obtain single unit recordings from this nucleus. The LSO EI cells were mostly sensitive to higher frequencies and showed Peristimulus Time Histograms (PSTHs) consisting of a sharp On response followed by a plateau when stimulated with Best Frequency (BF) tone bursts or noise bursts. This On response was sensitive to time and int such that ipsilateral time lead or intensity increase resulted in a stronger response. The response reached a minimum around zero time or int. No sharp peaks or dips were seen in the physiological range needed for localization, instead the response increased with increasing ipsilateral lead or intensity to the maximum values tested (2048 s time, 30 dB int). In the physiological range the time and int response were complementary (both increasing response as ipsilaterality was increased). Provided enough sound energy in the unit's sensitive region was present, the same time curves were produced when BF tone bursts, masked tone bursts, sharp onset tone bursts or noise bursts were used. Changing the time of the carrier of the tone burst alone had no effect (except for one cell with a BF of 560 Hz), only the relative time of arrival of the stimulus envelope seemed to be important. In contrast to these LSO EI cells MSO-type units showed EI or EE predominantly low frequency phase-locked responses. When stimulated with interaurally phase shifted (pha) BF tones the unit response was a cyclic function of pha. Some cells (all that were tested, n = 6 including the 560 Hz LSO EI cell) showed these cyclic responses when stimulated with noise bursts or non-BF tones. However, these characteristic delays were not necessarily in the physiological range, i.e. we could find no evidence that these units were responding to time/pha values corresponding to a particular sound source direction. In both LSO and MSO it seems that integration of information higher in the CNS from a population of these cells is necessary for unambiguous coding of sound source direction. The time intensity trading ratios measured in two MSO type cells (11 and 26 /dB) were clearly different to those measured in LSO EI cells (n = 6, 99–550 s/dB). These ratios correspond approximately to those of the psychophysical time and int images measured by Hafter and Jeffress (1968).Supported by the Deutsche Forschungsgemeinschaft (SFB 45)     

Effects of thalassaemic serum on the in vitro development of the malarial parasitePlasmodium falciparum

Sera from thalassaemic individuals were experimentally tested for their suppressive effects on the in vitro development of asexual stages ofPlasmodium falciparum. Cultures in sera collected from six patients who had classical haemoglobin H disease (-thal₁--thal₂) and six patients who had haemoglobin H disease with haemoglobin (Hb) Constant Spring (-thal₁-CS) showed a significantly higher degree of inhibition of parasite multiplication than cultures of thalassaemic erythrocytes in sera from healthy individuals. Similarly, sera from 12 patients with -thalassaemia/haemoglobin E (-thal-HbE) diminished parasite development in vitro. Schizonts ofP. falciparum cultured in erythrocytes from non-thalassaemic individuals containing normal Hb (₂₂) were also inhibited when thalassaemic serum was used in place of normal serum. The degree of inhibition was proportional to the concentration (vol/vol) of the thalassaemic serum.     

Rat Macrophage Inflammatory Protein-1α, a CC Chemokine, Acts as a Neutrophil Chemoattractant in Vitro and in Vivo

Recombinant rat macrophage inflammatory protein-1 (rMIP-1) at a concentration of 3 × 10^–8 M had strong neutrophil chemotactic activity, though the potency of rMIP-1 was less than that of cytokine-induced neutrophil chemoattractant (CINC)-1 at lower concentrations. In addition, rMIP-1 induced neutrophil chemotaxis in vivo when rMIP-1 was injected into the preformed air-pouch on the back of rats. The adhesion of rMIP-1-treated neutrophils to fibrinogen significantly increased, reaching a maximum adhesion at 10^–8 M. Stimulation of neutrophils with rMIP-1 induced a transient increase in intracellular free [Ca²⁺] dose-dependently. rMIP-1 still induced an increase in the intracellular [Ca²⁺] of rat neutrophils stimulated first with CINC-1, CINC-3 or C5a, suggesting that rat neutrophils have a specific receptor for rMIP-1. Supporting these findings, an additive increase in chemotactic potency was found when both rMIP-1 and CINC-1 were added to the lower wells of Boyden chamber in vitro. In addition, high levels of rMIP-1 were detected in the inflammatory site of air-pouch/carrageenan-induced inflammation in rats. Our results suggest that rMIP-1 acts as a neutrophil chemoattractant and, together with CINCs, plays an important role in infiltration of neutrophils into inflammatory sites in rats.     

Neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes: role of the α subunit in agonist sensitivity and desensitization

Neuronal nicotinic acetylcholine receptors (nAChRs) were expressed in Xenopus laevis oocytes after nuclear injection of complementary deoxyribonucleic acid (cDNA) expression vectors. The two receptor subtypes 4/n1 and 3/n1 were readily distinguishable from one another by ACh sensitivity and desensitization. 3/n1 receptors showed lower ACh sensitivity and stronger desensitization than 4/n1 receptors. Furthermore, although the current/voltage relationship was very similar in both receptor subtypes, the voltage dependence of desensitization was found to be strikingly different. As the n1 subunit was unchanged, the subunits must be responsible for these functional differences. Symmetric hybrid cDNAs, 43 and 34, were constructed and functional receptors were obtained by co-injection with n1. These hybrid receptors displayed an ACh sensitivity that was mainly defined by the extracellular sequence of the subunit. In contrast, no part of the subunit was found fully to determine desensitization.     

Immunohistochemical localization of αl-antitrypsin and αl-antichymotrypsin in salivary pleomorphic adenomas

Summary Immunohistochemical identification of l-antitrypsin (l-AT) and l-antichymotrypsin (l-ACh) in pleomorphic adenomas of salivary glands is reported in order to compare their distribution profiles with those of lysozyme and lactoferrin, already described elsewhere.Normal salivary glands indicated positive l-AT staining in ductal segments and had no l-ACh in any glandular cell. Pleomorphic adenomas displayed moderate positivity to l-AT staining in duct-like, tubular and glandular epithelia which was particularly intense in luminal cells. The limited number of tumour cells which showed duct-like structures with a single cellular layer arrangement, displayed the highest staining to l-ACh. Strongly l-AT positive tumour cells located on the inner side of luminal cavities were also markedly positive to l-ACh. Spindle shaped tumour cells existed outside tubular and ductal structures and were negative to l-AT and l-ACh.Distribution of l-AT in salivary glands was similar to that of lysozyme as is usual in ductal segments or their transformed cells, and occurrence of l-ACh localization rather resembled that of lactoferrin, with occurrence in acinar compartments and changed epithelia within acini.The biological role of a specific immunohistochemical distribution of l-AT and l-ACh in pleomorphic adenomas may be associated with a self regulating mechanism which inhibits degradation by tissue proteinases.     

Differential Regulation of IL-8 by IL-1β and TNFα in Hyaline Membrane Disease

Mechanisms that regulate cytokine-mediated inflammation in the lungs of preterm infants, including factors which regulate production of the chemokine IL-8, remain poorly defined. Sequential bronchoalveolar lavage samples were obtained from preterm newborns with hyaline membrane disease over a 28-day period. Bronchoalveolar lavage cell cytokine relationships were evaluated and the differential regulation of IL-8 by IL-1 and TNF was studied in a short-term culture system. In vivo, IL-8 and IL-l protein levels correlated closely with each other and with macrophage counts. In cell culture, exogenous anti-IL-1 antibody led to a 40% maximum inhibition (approximately) of IL-8 production by lipopolysaccharide stimulated lung inflammatory cells. Comparable amounts of exogenous anti-TNF antibodies achieved a 15% maximum inhibition (approximately) of IL-8 production. Anti-IL-1 and anti-TNF antibodies in combination did not inhibit IL-8 production beyond that achieved by anti-IL-l antibody alone. These results, in preterm newborns, support the concept of lung inflammation mediated in part by a macrophage, IL-1, and IL-8 cell cytokine pathway. The results also suggest that factors other than IL-1 and TNF regulate IL-8 expression in the lungs of preterm infants.     

δ-Aminolävulinacidurie Ein neues biochemisches und diagnostisches Kriterium der Bleivergiftung

Zusammenfassung Die Ausscheidung der -Aminolävulinsäure im Harn wurde bei 15 Bleivergiftungen und 140 Bleiarbeitern untersucht. Bei allen Bleivergiftungen fand sich eine beträchtlich vermehrte Ausscheidung von -Aminolävulinsäure. Von den 140 Bleiarbeitern zeigten 90 (=64%) eine pathologisch gesteigerte Ausscheidung von -Aminolävulinsäure. Weitere Untersuchungen sind notwendig, um die endgültige Zuordnung erhöhter -Aminolävulinsäurewerte zu Bleiaufnahme, Bleieinwirkung und Bleikrankheit zu klären. Die isolierte -Aminolävulinacidurie stellt ein neues biochemisches und diagnostisches Kriterium der Bleivergiftung dar. Sie kann als derzeit empfindlichster Indicator für die Bleiintoxikation gelten. Die -Aminolävulinacidurie wird auf einen toxischen Stoffwechselblock (Hemmung der SH-haltigen -Aminolävulinsäuredehydrase?) zwischen -Aminolävulinsäure und Porphobilinogen im Rahmen der Biosynthese des Protoporphyrins und des Hämoglobins zurückgeführt.Mit Unterstützung des Stifterverbandes für die Deutsche Wissenschaft und der Unterharzer Berg- und Hüttenwerke GmbH.     

Activated charcoal is as effective as fuller's earth or bentonite in paraquat poisoning

Summary In vitro investigations have shown that the adsorption capacity of activated charcoal (Kohle-Compretten, Ultracarbon, E. Merck, Darmstadt, FRG) is just as high as that of Fuller's earth (Surrey powder, Laporte Industries Ltd., Luton, GB) or Bentonite BP W.B. (Steetley Minerals Ltd., Milton Keynes, GB). Fuller's earth (Fullererde) from another manufacturer has had very poor adsorption properties and is thus not suitable for the treatment of paraquat poisoning. Animal experiments have shown that the curative effect of activated charcoal given 0.5, 1, 2, and 3 h after ingestion of 200 and 300 mg paraquat/kg body weight is equally as good or even better than that of Fuller's earth or Bentonite BP W.B.. Activated charcoal is a substitute of equal value to these mineral soils.     

The role ofγδ T cells in the normal and disordered immune system

Summary A small population of T cells does not express the conventional T cell receptor characterized by the and polypeptide chains (TCR) but instead, two polypeptides termed and (TCR). This alternative receptor is able to recognize antigen. It appears early in T cell ontogeny, but its role in the thymus prior to the availability of TCR remains unclear. In selected sites such as skin or gut TCR predominates in mice which might suggest a role of T cells in the first line of defense against infection, T cells secrete lymphokines and display cytotoxic activity. However, their activation requirements may differ from what is known for T cells since MHC-nonrestricted and also CD4 and CD8 negative T cells have been described. Preferential activation by mycobacterial antigens possibly indicates a special repertoire of the T cells. In various diseases slightly increased numbers of T cells were found, but these preliminary studies have not yet provided evidence for a major pathogenetic role of T cells.List of abbreviations C constant region (immunoglobulin or TCR gene segment) - CD4 cluster of differentiation 4 (mainly on helper cells) - CD8 cluster of differentiation 8 (mainly on cytotoxic cells) - D diversity region (immunoglobulin or TCR gene segment) - DNA desoxyribonucleic acid - IL2 interleukin 2 - J joining region (immunoglobulin or TCR gene segment) - kD kiloDalton - MHC major histocompatibility complex - NK natural killer (cells) - RA rheumatoid arthritis - TCR T cell receptor - V variable region (immunoglobulin or TCR gene segment)