Korrelation zwischen der Blutkörperchensenkung und Plasmaproteinen

Zusammenfassung Die BKS und 12 Plasmaproteine von 21 Kranken mit unterschiedlichen Krankheiten wurden statistisch miteinander verglichen. Dabei ergaben sich positive Korrelationen zwischen der BKS und dem sauren content/h156pvp544610171/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₁-Glykoprotein und der BKS und dem content/h156pvp544610171/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₁-Antitrypsin, eine negative Korrelation zwischen der BKS und dem Transferrin. Außerdem korrelierten das saure content/h156pvp544610171/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₁-Glykoprotein und das content/h156pvp544610171/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₁-Antitrypsin sowie das saure content/h156pvp544610171/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₁-Glykoprotein und das Transferrin miteinander. Bei der Deutung dieser Ergebnisse müssen einerseits Gemeinsamkeitskorrelationen in Betracht gezogen werden, zum anderen die Möglichkeit, daß zwischen bestimmten Proteinmustern und der BKS Zusammenhänge bestehen.     

β-Adrenergic receptor coupled-adenylate cyclase of human fat cell ghosts

Summary The effects of beta-adrenergic agonists such as isoproterenol, norepinephrine and epinephrine upon the adenylate cyclase activity of human fat cell ghosts were tested, each alone and in combination with the beta-blocking agent propranolol. Saturating concentrations of these agents showed a 2–6.5-fold increase of enzyme activity without addition of any artificial cofactors. Isoproterenol was more potent in stimulating the enzyme system than epinephrine and nor-epinephrine. Propranolol caused a dose-dependent rightward shift of the log-dose response curve of these beta-adrenergic agonists. The assay of human fat cell adenylate cyclase in vitro may provide a simple and convenient assay system for the screening of beta-adrenergic drugs of potential therapeutic importance.Herrn Prof. Dr. Dr. h.c. G. Schettler zum 60. Geburtstag gewidmet     

TGF-β1 Null Mutation Leads to CD154 Upregulated Expression in Affected Tissues

The TGF-content/kj40086rr5641j37/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">1(–/–) mouse is a murine model for systemic autoimmune disease. The aim of this study is to elucidate the immunological mechanism that leads to multifocal tissue inflammation and autoantibody production in TGF-content/kj40086rr5641j37/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">1(–/–) mice. Heart, lung, liver, and salivary gland from TGF-content/kj40086rr5641j37/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">1(–/–) were assessed for CD154 expression by RT-PCR and immunohistochemistry. Compared to wild-type littermates, CD154 expression was elevated in all tissues studied. Furthermore, IL-12 mRNA was expressed in the salivary gland and heart of TGF-content/kj40086rr5641j37/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">1(–/–) mice and not in wild-type littermates. This suggests that the CD154 pathway is activated in these tissues. This shows that TGF-content/kj40086rr5641j37/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">1 regulates CD154 expression leading to spontaneous IL-12 production and autoimmunity.     

Morphine-6beta-glucuronide modulates the expression of inducible nitric oxide synthase

The immunomodulatory effects of morphine are well established; however, suprisingly little is known about the immunomodulatory properties of the major metabolites of morphine. The present study tests the hypothesis that expression of inducible nitric oxide synthase (iNOS) is modulated by the administration of the morphine metabolite, morphine-6content/w545540m7h27u0j5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-glucuronide. The initial study using rats shows that morphine-6content/w545540m7h27u0j5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-glucuronide administration (0, 1.0, 3.163, 10 mg/kg s.c.) results in a pronounced reduction in lipopolysaccharide (LPS)-induced expression of iNOS (inducible nitricoxide synthease) in spleen, lung, and liver tissue as measured by western blotting. Morphine-6content/w545540m7h27u0j5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-glucuronide also produces a reduction in the level of plasma nitrite/nitrate, the more stable end-product of nitric oxide degradation. In a subsequent study, administration of the opioid receptor antagonist, naltrexone (0.1 mg/kg) prior to the injection of morphine-6content/w545540m7h27u0j5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-glucuronide (10 mg/kg) blocks the morphine-6content/w545540m7h27u0j5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-glucuronide induced reduction of iNOS expression and plasma nitrite/nitrite levels indicating that the effect is mediated via the opioid-receptor. This study provides the first evidence that morphine-6content/w545540m7h27u0j5/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-glucuronide alters the expression of iNOS.     

Acidic ATP activates lymphocyte outwardly rectifying chloride channels via a novel pathway

Using whole-cell patch-clamp techniques we found that ATP activated an outwardly rectifying current in Daudi human B lymphoma cells under acidic conditions. The substitution of Cl^– for gluconate^– shifted the reversal potential, while Cl^– channel blockers, 4,4content/2aefe9xhw86h6amd/xxlarge8217.gif" alt="rsquo" align="BASELINE" BORDER="0">-diisothiocyanostibene-2,2content/2aefe9xhw86h6amd/xxlarge8217.gif" alt="rsquo" align="BASELINE" BORDER="0">-disulfonic acid (DIDS) and 9-anthracene carboxylic acid (9-AC), blocked the current, indicating that ATP induces this current by activating the outwardly rectifying chloride channel (ORCC). The effect of ATP on ORCC was mimicked by ADP, but not by other P2 receptor agonists such as ATPcontent/2aefe9xhw86h6amd/xxlarge947.gif" alt="gamma" align="MIDDLE" BORDER="0">S (a poorly hydrolyzable analog of ATP), 2content/2aefe9xhw86h6amd/xxlarge8217.gif" alt="rsquo" align="BASELINE" BORDER="0">,3content/2aefe9xhw86h6amd/xxlarge8217.gif" alt="rsquo" align="BASELINE" BORDER="0">-O-benzoyl-4-benzoyl-ATP (BzATP), and UTP. The ATP-induced ORCC current was completely blocked by 100 content/2aefe9xhw86h6amd/xxlarge956.gif" alt="mgr" align="MIDDLE" BORDER="0">M suramin (a P2 receptor antagonist), and was partially blocked by 100 content/2aefe9xhw86h6amd/xxlarge956.gif" alt="mgr" align="MIDDLE" BORDER="0">M pyridoxal-phosphate-6-azophenyl-2content/2aefe9xhw86h6amd/xxlarge8217.gif" alt="rsquo" align="BASELINE" BORDER="0">,4content/2aefe9xhw86h6amd/xxlarge8217.gif" alt="rsquo" align="BASELINE" BORDER="0">-disulfonic acid tetrasodium (PPADS), which is another P2 receptor antagonist. Neither inactivation of G proteins nor elimination of extracellular Ca²⁺ affected the ATP-induced current, indicating that G protein-coupled P2Y receptors and Ca²⁺-permeable P2X receptors are not involved. Based on the pharmacological profile and the fact that acidic conditions are required for ATP to activate the ORCC, we suggest that acidic ATP activates the lymphocyte ORCC via a novel pathway, which is not associated with any previously described purinergic receptors.     

Adjustment of metabolism,catecholamines and β-adrenoceptors to 90 min of cycle ergometry

Adrenaline infusion of 0.1 content/p458t4180832p787/xxlarge956.gif" alt="mgr" align="MIDDLE" BORDER="0">g · kg^–1 · min^–1 in healthy volunteers results in an increase of hepatic glucose production, an increase of the absolute number of occupied content/p458t4180832p787/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptors and specific changes in metabolism. To compare these effects with the changes induced by an endogenous catecholamine release, we investigated healthy volunteers during cycle ergometry. After fasting at least 14 h seven healthy subjects exercised for 90 min at an intensity of 20% below their individual anaerobic threshold. The rate of glucose production as well as the turnover rates of alanine and leucine were calculated using stable isotope tracers. High and low affinity content/p458t4180832p787/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenergic binding sites on lymphocytes were determined by an equilibrium binding assay with (–)¹²⁵ Iodocyanopindolol. After 90 min of cycling the rate of appearance of glucose increased significantly from means of 2.0 (SD 0.2) to 2.65 (SD 0.50) mg · kg^–1 · min^–1 with unchanged blood concentrations of glucose and lactate. The flux of the amino acids alanine and leucine decreased significantly from means of 0.91 (SD 0.21) to 0.62 (SD 0.14) mg · kg^–1 · min^–1 and from 0.40 (SD 0.05) to 0.32(SD 0.04) mg · kg^–1 · min^–1, respectively. The mean free fatty acid concentration increased significantly from 0.65 (SD 0.33) to 1.27 (SD 0.45) mmol · l^–1 during the endurance trial. The increase of glucose turnover and the decrease of amino acid flux point to a metabolic shift towards enhanced utilization of free fatty acids. Adrenaline and noradrenaline concentrations showed a moderate but significant increase from means of 0.61 (SD 0.20) to 0.99 (SD 0.36) nmol · l^–1 and from 2.27 (SD 0.75) to 3.46 (SD 0.38) nmol · 1^–1, respectively. The number of high affinity content/p458t4180832p787/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenergic binding sites per cell (content/p458t4180832p787/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptors) nearly doubled from 770 (SD 130) to 1490 (SD 150) during 90 min of cycling. The observed endogenous plasma catecholamine concentrations were not sufficient to change significantly the relative receptor occupancy. This would seem to indicate that the aerobic exercise induced effects depended more on the absolute number of occupied content/p458t4180832p787/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptors than on their relative receptor occupancy. When compared to the results of the adrenaline infusion experiment the increases of the hepatic glucose production and the increase of content/p458t4180832p787/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptors were very similar in both groups despite ten times higher adrenaline plasma concentrations in the infusion group. This would seem to indicate that content/p458t4180832p787/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptors mediated effects do not correlate with catecholamine plasma concentrations.     

Inhibition of ω-conotoxin-sensitive Ca2+ channel currents by internal Mg2+ in cultured rat cerebellar granule neurones

The effects of changing the intracellular concentrations of either free Mg²⁺ ions ([Mg²⁺]_i) or Mg²⁺-bound adenosine triphosphate ([Mg · ATP]_i) on Ca²⁺ channel currents were assessed in cultured rat cerebellar granule neurones using the whole-cell patch-clamp technique. Raising [Mg²⁺]_i from 0.06 mM to 1.0 mM inhibited Ca²⁺ channel currents by approximately 50%. The action of content/v821331000248726/xxlarge969.gif" alt="ohgr" align="BASELINE" BORDER="0">-conotoxin GVIA (content/v821331000248726/xxlarge969.gif" alt="ohgr" align="BASELINE" BORDER="0">-CgTX), a selective inhibitor of content/v821331000248726/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">Ncontent/v821331000248726/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0">-type Ca²⁺ channels was also investigated. With increasing [Mg²⁺]_i, the proportion of current irreversibly blocked by content/v821331000248726/xxlarge969.gif" alt="ohgr" align="BASELINE" BORDER="0">-CgTX was reduced, and was negligible (approximately 5 pA of current) in the presence of [Mg²⁺]_i values of 0.5 mM or greater. Block of the content/v821331000248726/xxlarge969.gif" alt="ohgr" align="BASELINE" BORDER="0">-CgTX-sensitive current accounted for the reduction in total current by concentrations of [Mg²⁺]_i to 0.5 mM. Raising [Mg²⁺]_i had no effect on the rate of decay of Ca²⁺ currents, but did produce a negative shift in current activation, possibly due to a non-specific interaction with negative surface charge. Altering [Mg · ATP]_i from 0.3 to 5.0 mM caused a twofold increase in the size of currents without affecting the proportion of current sensitive to content/v821331000248726/xxlarge969.gif" alt="ohgr" align="BASELINE" BORDER="0">-CgTX. [Mg²⁺]_i was also effective in inhibiting the Ca²⁺ channel current following potentiation by increasing [Mg · ATP]_i. These data suggest that content/v821331000248726/xxlarge969.gif" alt="ohgr" align="BASELINE" BORDER="0">-CgTX-sensitive current in these cells is selectively inhibited by internal Mg²⁺ whereas both content/v821331000248726/xxlarge969.gif" alt="ohgr" align="BASELINE" BORDER="0">-CgTX-sensitive and -resistant components of current are potentiated by internal Mg · ATP. The mechanism by which Mg²⁺ inhibits content/v821331000248726/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">Ncontent/v821331000248726/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0">-type channels is unclear, but may involve an open channel block.     

Sequence analysis of cDNAs for the human and bovine ATP synthase β subunit: mitochondrial DNA genes sustain seventeen times more mutations

We have cloned and sequenced human and bovine cDNAs for the content/nrl2000534646340/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0"> subunit of the ATP synthase (ATP-synß), a nuclear DNA (nDNA) encoded oxidative phosphorylation (OXPHOS) gene. The two cDNAs were found to share 99% amino acid homology and 94% nucleotide homology. The evolutionary rate of ATPsynß was then compared with that of two mitochondrial DNA (mtDNA) ATP synthase genes (ATPase 6 and 8), seven other mtDNA OXPHOS genes, and a number of nuclear genes. The synonymous substitution rate for ATPsynß proved to be 1.9 × 10^–9 substitutions per site per year (substitutions × site^–1 × year^–1) (SSY). This is less than 1/2 that of the average nDNA gene, 1/12 the rate of ATPase 6 and 8, and 1/17 the rate of the average mtDNA gene. The synonymous and replacement substitution rates were used to calculate a new parameter, the content/nrl2000534646340/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">selective constraint ratiocontent/nrl2000534646340/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0">. This revealed that even the most variable mtDNA protein was more constrained than the average nDNA protein. Thus, the high substitution mutation rate and strong selective constraints of mammalian mtDNA proteins suggest that mtDNA mutations may result in a disproportionately large number of human hereditary diseases of OXPHOS.     

Microwave Spectroscopy of Myocardial Ischemia and Infarction. 2. Biophysical Reconstruction

The proposed dielectrical relaxation model of the myocardium in the microwave spectrum has been verified both on test solutions and on normal canine myocardium. Furthermore, the model was utilized to reconstruct the changes in tissue properties (including myocardial bulk resistance and water content) following myocardial acute ischemia and chronic infarction. It was shown that the reconstructed myocardial resistance and water content correlate dynamically with the process of the development of acute myocardial ischemic injury. In chronic cases the reconstructed resistance and water content of infarcted myocardium are significantly different from that of normal myocardium: the resistance is lower and water content is higher than in normal myocardium. © 2000 Biomedical Engineering Society. PAC00: 8764-t, 8719Xx     

Localisation of CEA, β-HCG,SP1, and keratin in the tissue of lung carcinomas

Summary One hundred and twenty seven cases of lung tumors were studied by the immunoperoxidase technique for the presence of CEA andcontent/t86227n566273674/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-HCG. Twenty-nine of these tumors were additionally stained for keratin and SP1. CEA and SP1 could be demonstrated in 80% of the studied cases, whilecontent/t86227n566273674/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-HCG was found in only 9%. SP1 revealed an almost identical staining pattern to CEA and keratin was found only in squamous cell carcinomas. The tissue positivity of none of these three markers correlated with tumor size, lymphnodal involvement or histological type.This study was supported by content/t86227n566273674/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">Deutsche Stiftung für Krebsforschung - Dr. Mildred Scheel-Stiftungcontent/t86227n566273674/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0">