Cholinesterases of heart muscle. Characterization of multiple enzymes using kinetics of irreversible organophosphorus inhibition.

Cholinesterases of porcine left ventricular heart muscle were characterized with respect to substrate specificity and inhibition kinetics with organophosphorus inhibitors N,N'-di-isopropyl-phosphorodiamidic fluoride (Mipafox), di-isopropylphosphorofluoridate (DFP), and diethyl p-nitro-phenyl phosphate (Paraoxon). Total myocardial choline ester hydrolysing activity (234 nmol/min/g wet wt with 1.5 mM acetylthiocholine, ASCh; 216 nmol/min/g with 30 mM butyrylthiocholine, BSCh) was irreversibly and covalently inhibited by a wide range of inhibitor concentrations and, using weighted least-squares non-linear curve fitting, residual activities as determined with four different substrates in each case were fitted to a sum of up to four exponential functions. Quality of curve fitting as assessed by the sum of squares reached its optimum on the basis of a three component model, thus, indicating the presence of three different enzymes taking part in choline ester hydrolysis. Final classification of heart muscle cholinesterases was obtained according to both substrate hydrolysis patterns with ASCh, BSCh, acetyl-beta-methylthiocholine and propionylthiocholine, and second-order rate constants for the reaction with organophosphorus inhibitors Mipafox, DFP, and Paraoxon. One choline ester-hydrolysing enzyme was identified as acetylcholinesterase (EC 3.1.1.7), and one as butyrylcholinesterase (EC 3.1.1.8). The third enzyme with relative resistance to organophosphorus inhibition was classified as atypical cholinesterase.     

Das Verhalten des Druckes in der Herzwand

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Das Verhalten von Blutdruck und Stromzeitvolumen in der Pfortader bei intraabdomineller Drucksteigerung

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Effects of CNS temperature on generation and transmission of temperature signals in homeotherms a common concept for mammalian and avian thermoregulation

Neurophysiological studies on avian hypothalamic thermosensitivity have presented evidence for a higher Q₁₀ of cold than of warm signal transmission in the CNS of birds. An identical temperature dependence of central cold and warm signal transmission in mammals is suggested by considerations on the phylogeny of temperature regulation. By taking into account the experimental evidence for the existence of thermosensory afferents in the CNS of mammals and birds, being differently developed in the various sections of the neural axis and exerting quantitatively different influences on the various thermoregulatory effectors, a common concept of homeothermic thermoregulation is proposed resting on the same basic assumptions for mammals and birds. The great diversity of negative as well as positive feedback effects of CNS temperature displacements on homeothermic thermoregulation, which is particularly expressed in avian autonomic and behavioral thermoregulation and, further, certain pathophysiological conditions of disturbed thermoregulation could be accounted for by assuming quantitatively different contributions of the central thermosensory inputs to thermoregulatory effector control, but maintaining the Q₁₀ values of hypothalamic warm and cold signal transmission constant. The proposed model, while basically additive in its mathematical design, meets a number of properties described by multiplicative models of thermoregulation. It additionally generalizes these models by predicting that changes of hypothalamic temperature modify the sensitivities with which any thermoregulatory effector responds to any thermosensory input.Dedicated to Professor Dr. Dr. h. c. Rudolf Thauer on the occasion of his 75th birthday     

Klinische Beurteilung von Coronardilatatoren

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The clinical evaluation of coronary dilators

     

Interstitial loss and gain of sequences on chromosome 22 in meningiomas with normal karyotype

In nearly half of sporadic low grade meningiomas no chromosome aberration can be detected. In the majority of the other half chromosome 22 is lost. In higher grade meningiomas this loss is followed by characteristic secondary chromosome aberrations. Regarding the molecular findings in Schwannomas, homozygous loss or mutation of the NF2 gene located on chromosome 22, was supposed also to be the primary event in meningioma development. However, in nearly all high grade but in only a minority of low grade meningiomas the loss of the NF2 protein is observed. Therefore, both the hypothetical combined heterozygous loss of or inactivation of two or more tumour suppressor genes (at least one of them located on chromosome 22) or the homozygous loss of a regulatory gene on chromosome 22 different from NF2 was discussed. In search for microdeletions or/and structural recombinations of chromosome 22 we investigated primary cell cultures of 43 meningiomas by conventional G-banding (26 without, 17 with loss of chromosome 22). Twenty-seven tumours were analysed with spectral karyotyping (SKY) and 16 with fluorescence in situ hybridisation (FISH) with DNA probes for the chromosomal regions of 22q11.2, 22q11.23q12.1, 22q12.1 and 22q13.3. SKY analysis confirmed G-banding data for chromosome 22 and could specify marker chromosomes and translocations containing material from chromosome(s) 22. Confirming our assumption microdeletions on chromosome 22 were detected by FISH in 6/8 cytogenetically non-aberrant meningiomas. Surprisingly, in 2/8 cases we observed gains of the 22q13.3 and in 2/8 gains of the 22q12.1 region. Here we present first evidence for an uncommon mechanism during early meningioma development at least for a meningioma subgroup: i) duplication and translocation of sequences from chromosome 22 to different chromosomes. ii) deletion of the original sequences on chromosome 22, resulting in disomy again (only visible as translocation in metaphase FISH). iii) loss of chromosome 22.