Prostaglandin-like substances inPropionibacterium acnes. V. Activity profiles using cascade superfusion bioassay and platelet aggregation

Summary The activity spectrum of prostaglandin-like substances (PLS) fromP. acnes was investigated with cascade superfusion technique and by platelet aggregation assay. The biological activity of PLS resembles that of PGI₂: both relax bovine coronary artery, rabbit mesentric and coeliac arteries; both contract the rat stomach strip as well as both typically inhibit spontaneous movements of isolated guinea pig ileum. Also, similarly to PGI₂, PLS inhibits platelet aggregation regardless the inducer used. However, PLS possesses a specific antiaggregatory pattern on platelet, which indicates that these compounds are not indentical with primary prostaglandins or PGI₂.     

Evidence that the prostaglandin-like substances fromPropionibacterium acnes are not identical with PGE2

Summary The prostaglandin-like substances (PLS) isolated fromP. acnes were investigated by reversed phase chromatography and gas chromatography-mass spectrometry. These analyses demonstrated that PLS were not identical with PGE₂, which supports a concept of PLS as a potential mediator of the inflammatory process in acne vulgaris.     

Prostaglandin-like substances inPropionibacterium acnes II. Stimulatory effect on ovarian cyclic AMP

Summary The prostaglandin-like substances (PLS) fromPropionibacterium acnes increased the ovarian tissue levels of cyclic AMP (cAMP) approximately 2-fold. The lipid material extracted fromP. acnes thus behaved like PG's of the E-type, and since it is unlikely that other known stimulators of the ovarian cAMP system can be present in the bacterial lipid fraction, these experiments give further evidence in favour of the occurrence of PLS inP. acnes.     

Experimenteller Nachweis der autochthonen Automatie der Lymphgefässe

Summary It is shown that the peristaltic activity of the isolated mesenterial-lymph vessels of mammals (Cavia porcellus L.) is provoked by two different stimuli:1. by extension (internal pressure of the vessel: 2–25 cm H₂O); 2. by temperature (biokinetic Temperature-Space of 23°; between 22–45°C).Based on these experiments, the autochthonous automaticy of the lymph vessels has been proved.

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Meiner Assistentin, FrauDora Rathenow-Mercier, danke ich für hervorragende Mitarbeit, der Deutschen Forschungsgemeinschaft für die apparative Unterstützung.     

Prostaglandin-like substances in Propionibacterium acnes. III. Differential contractile effects on smooth muscle layers of the human utero-tubal junction.

The biological activity of a lipid fraction extracted from P. acnes was tested on isolated smooth muscle strips from the human utero-tubal junction. The bioassay experiments support the concept that prostaglandin-like substances (PLS) occur in P. acnes. However, in the bioassay system used, the effect of PLS was different from that of PGF2 alpha and PGI2 but similar, although not identical, to that of arachidonic acid and PGE2.     

The effect of acidic polysaccharides and prostaglandin-like substances isolated fromPropionibacterium acnes on granulocyte chemotaxis

Summary Three acidic polysaccharide (AP) fractions and the prostaglandin-like substances (PLS) isolated fromP. acnes were investigated regarding their chemotactic activities on polymorphonuclear leukocytes. Both AP's and PLS induced a significant chemotactic response, which suggests their involvement in inflammatory acne vulgaris.     

Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism

The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2 (ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined K_m values ranged from 0.05 to 0.3 μM and k_cat values from 2.3 to 17.6 min⁻¹, while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup. This mutation increased the retinoid activity up to 100-fold. The K_m values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic retinol oxidation at physiological concentrations. Received 12 October 2006; received after revision 6 December 2006; accepted 8 January 2007     

Kinetik der hepatischen Farbstoffaufnahme von Indocyaningrün. Einfluss von Bilirubin und Natriumglykocholat

Summary Kinetics of hepatic uptake of indocyanine green, a dye which is used for evaluation of liver function, were studied in the rat. The results indicate that the relationship between ICG-dose and initial hepatic dye uptake obeys Michaelis-Menten kinetics suggesting an interaction of the dye with a carrier or fixed site in the liver cell. Thus it was possible to calculate maximum ICG-uptake (v _max ) and the Michaelis constant (K _m ) of this transport system from several submaximal values.v _max was 7.65 (6-06-9.65)²² mg per 100 g liver/min and K _m 0.56 (0.31–0.81)²². Under the influence of substances which inhibit the elimination of dyes by the liver the parametersv _max and K _m showed changes which allowed characterization of the type of inhibition. While sodium glycocholate had no influence on maximum hepatic ICG-uptake and the Michaelis constant bilirubin caused a significant increase of K _m to 1.29 (0.68–1.90)²² without significantly changingv _max . These data suggest that bilirubin interferes with hepatic uptake of indocyanine green by competitive inhibition and that uptake of bile acids is dependent on a different mechanism.     

Gain of function of TMEM16E/ANO5 scrambling activity caused by a mutation associated with gnathodiaphyseal dysplasia

Mutations in the human TMEM16E (ANO5) gene are associated both with the bone disease gnathodiaphyseal dysplasia (GDD; OMIM: 166260) and muscle dystrophies (OMIM: 611307, 613319). However, the physiological function of TMEM16E has remained unclear. We show here that human TMEM16E, when overexpressed in mammalian cell lines, displayed partial plasma membrane localization and gave rise to phospholipid scrambling (PLS) as well as non-selective ionic currents with slow time-dependent activation at highly depolarized membrane potentials. While the activity of wild-type TMEM16E depended on elevated cytosolic Ca²⁺ levels, a mutant form carrying the GDD-causing T513I substitution showed PLS and large time-dependent ion currents even at low cytosolic Ca²⁺ concentrations. Contrarily, mutation of the homologous position in the Ca²⁺-activated Cl^? channel TMEM16B paralog hardly affected its function. In summary, these data provide the first direct demonstration of Ca²⁺-dependent PLS activity for TMEM16E and suggest a gain-of-function phenotype related to a GDD mutation.     

Cannflavin A and B,prenylated flavones fromCannabis sativa L.

Summary Two novel prenylat flavones, termed Cannflavin A and B, were isolated from the cannabinoid free ethanolic extract ofCannabis sativa L. Both compounds inhibited prostaglandin E₂ production by human rheumatoid synovial cells in culture.This communication is dedicated to the memory of the late Professor J. W. Fairbairn and the late Dr. J. T. Pickens. We are grateful to the Medical Research Council for a project grant and to Ms J. Elliot of King's College London for NMR spectra.     

Zur klinischen Bedeutung des autoradiographischen Verfahrens bei der Verwendung von kurzlebigen künstlichen radioaktiven Isotopen (Autoorganographie,Autoangiographie)

Summary The author demonstrates the possibility to realize on living human individuals big sizeautoradiographs afterintravenous injections of an artificial radioactive isotope of a relatively short activity. Strong preparations (100 millicuries) of radiozinc (Zn⁶³) in form of soluble oxide have been employed. These injections were performed on two patients suffering from general carcinosis. The humanauto-organographs (autohepatographs, automammographs, autonephrographs, etc.), as well as theautoangiographs of the blood vessels of the skin and the subcutaneous tissues, thus realized for the first time, are quite interesting. The possibilities of a clinical utilization of such autoradiographs are briefly discussed.     

Sopra un caso particolare della superficie F 4 (3) di M. Noether

Summary The Noetherian surfaceF ₄ ⁽³⁾ , which is represented on a plane by a linear ³ system ofC ₉(A ₁ ³ A ₂ ³ A ₃ ³ A ₄ ³ A ₅ ³ A ₆ ³ A ₇ ³ A ₈ ³ A ₉ ² A ₁₀), possesses generally only one linear pencil of elliptic cubics. IfA _i (i=1, 2, , 9) are the basis points of aHalphen pencil ofC ₉,A ₁₀ is infinitely near toA ₉, and in this caseF ₄ ⁽³⁾ is a not trivial example of such a surface with two pencils of elliptic cubics.     

Chromogranin A: a novel susceptibility gene for essential hypertension

Chromogranin A (CHGA) is ubiquitously expressed in secretory cells of the endocrine, neuroendocrine, and neuronal tissues. Although this protein has long been known as a marker for neuroendocrine tumors, its role in cardiovascular disease states including essential hypertension (EH) has only recently been recognized. It acts as a prohormone giving rise to bioactive peptides such as vasostatin-I (human CHGA_1–76) and catestatin (human CHGA_352–372) that exhibit several cardiovascular regulatory functions. CHGA is over-expressed but catestatin is diminished in EH. Moreover, genetic variants in the promoter, catestatin, and 3′-untranslated regions of the human CHGA gene alter autonomic activity and blood pressure. Consistent with these findings, targeted ablation of this gene causes severe arterial hypertension and ventricular hypertrophy in mice. Transgenic expression of the human CHGA gene or exogenous administration of catestatin restores blood pressure in these mice. Thus, the accumulated evidence establishes CHGA as a novel susceptibility gene for EH.     

The dimeric and co-operative myoglobin ofNassa mutabilis. A peculiar case

The myoglobin present in the radular muscle of the Prosobranchia sea snailNassa mutabilis is a peculiar case among myoglobins. It is a dimer showing co-operative oxygen binding equilibrium curves with pO_{2 1/2}=4.7 mmHg, invariant with pH, and n=1.6. Although the globin is composed of 147 amino acid residues, corresponding to a molecular mass of 15760 D, gel filtration chromatography of the native myoglobin indicate Mr=26000±2000 D. Similarly, acrylamide electrophoretic analyses in SDS and velocity sedimentation indicate a molecular mass of about 13000 D for the denatured globin. The molecule is highly unstable and forms slowly a chromogen when aged or immediately upon oxidation to the ferric state. The visible region of the absorption spectrum of the O₂ or CO liganded myoglobin derivatives indicate an altered heme environment. Circular dichroism analyses confirm this indication showing negative Cotton effects in all regions of the heme absorption spectra of the MbO₂ and MbCO derivatives. Interestingly, the CD spectrum of the oxidised met-form shows a positive band almost symmetrical with respect to that of the MbO₂ derivative. This is similar to what reported for the monomeric hemoglobin ofGlycera dibranchiata for which a reversed heme orientation was proposed. Detailed resonance Raman spectroscopic studies have permitted a more direct investigation of the interactions between the heme and the protein. The proximal Fe-Im bond shows a stretching mode frequency down shifted by 5 cm^–1 with respect to the corresponding band of horse heart myoglobin, in good correlation with the much higher instability ofNassa m. myoglobin and its much lower oxygen affinity. The unusual bond instability finds additional support in a kinetic study in which the myoblogin is mixed with CO in buffered solutions at different pH values. This approach gives evidence that the Fe-Im bond is broken upon lowering the pH, with a pK of 4.0±0.2, the highest among those of deoxy hemoproteins. The rupture of the proximal bond appears to occur with a proton-linked transition showing n=1.8±0.1, again indicating cooperativity between the two subunits. The vinyl and propionate heme substituents show resonance Raman spectroscopic bands indicating different modes of interaction with their environment with respect to other myoglobins. Most interestingly, the vinyl stretching mode frequency, typically a single band, appears split in two bands inNassa m. myoglobin. This splitting is evident in all the investigated derivatives of the myoglobin, indicating that vinyl 2 and 4 are not equivalent in this molecule. A similar splitting has been found so far only inChironomus t.t. hemoglobin.     

Enrichment of ligands with molecular dockings and subsequent characterization for human alcohol dehydrogenase 3

Alcohol dehydrogenase 3 (ADH3) has been assigned a role in nitric oxide homeostasis due to its function as an S-nitrosoglutathione reductase. As altered S-nitrosoglutathione levels are often associated with disease, compounds that modulate ADH3 activity might be of therapeutic interest. We performed a virtual screening with molecular dockings of more than 40,000 compounds into the active site of human ADH3. A novel knowledge-based scoring method was used to rank compounds, and several compounds that were not known to interact with ADH3 were tested in vitro. Two of these showed substrate activity (9-decen-1-ol and dodecyltetraglycol), where calculated binding scoring energies correlated well with the logarithm of the k _cat/K _m values for the substrates. Two compounds showed inhibition capacity (deoxycholic acid and doxorubicin), and with these data three different lines for specific inhibitors for ADH3 are suggested: fatty acids, glutathione analogs, and cholic acids.     

Does ammonium uptake influence xylem sap composition inPhaseolus vulgaris L. andGlycine max (L.) Merill?

The question of whether ammonium uptake influences the occurrence of ureides in legumes has been addressed in this study by investigating threeP. vulgaris genotypes as well as one cultivar ofGlycine max. All plants were raised in sand culture during the dry season in northern Thailand and irrigated daily with nitrogen-free nutrient solution, or the same solution containing 12 mol m^–3 nitrogen in the form of (NH₄)₂SO₄ or KNO₃, each treatment consisting of different proportions of either compound. Regression analyses of xylem sap composition relative to ammonium vs. nitrate supply of plants harvested at V4, R1 and R6 indicated close positive correlations of xylem amino nitrogen content and negative correlations with xylem nitrate content and ammonium supply. Statistically significant correlations between relative xylem ureide content and ammonium availability could be established for theP. vulgaris cultivar Brilliant up to stage R1, but not for the other plants investigated. It was concluded that at least for some genotypes of common bean a relationship exists between ureide production and ammonium uptake by the root system. Since the extent to which ureide production is stimulated remains quite small, its relevance to the xylem solute technique for measurement of N₂ fixation may be limited. Nevertheless, due to the possibility of large genotypic differences in the impact of ammonium on ureide production, this factor must be considered in calculations if N₂ fixation is to be determined in soils containing significant amounts of ammonium, e.g. in paddy fields.     

Über Struktur und Aktivität der den H2O2-Zerfall katalysierenden Cu2+-Komplexe. — VI. Differenzierung von nativer RNS und nativer DNS bzw. denaturierter DNS auf Grund der katalytischen Eigenschaften

Summary The catalysis of H₂O₂ decomposition by Cu²⁺-complexes of RNA and DNA has been investigated. It is shown that both complexes decompose H₂O₂, but only the Cu²⁺-RNA-system shows peroxidative activity too, e.g. only in this case the nucleotide bases are degraded. Thermal denaturation of DNA also leads to a Cu²⁺-complex with peroxidative activity, the latter being dependent on the degree of denaturation.

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V. Mitteilung:S. Petri, H. Sigel undH. Erlenmeyer, Helv. chim. Acta49, 1778 (1966).

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12. Mitteilung überMetallionen und H ₂ O ₂; 11. Mitteilung:H. Ch. Curtius, P. Anders, R. Zell, H. Sigel undH. Erlenmeyer, Helv. chim. Acta49, 2256 (1966).     

Temporal Aggregation in Dynamic Linear Models

One important aspect concerning the analysis and forecasting of time series that is sometimes neglected is the relationship between a model and the sampling interval, in particular, when the observation is cumulative over the sampling period. This paper intends to study the temporal aggregation in Bayesian dynamic linear models (DLM). Suppose that a time series Y_t is observed at time units t and the observations of the process are aggregated over r units of time, defining a new time series Z_k=Σ^r_i=1Y_rk+i. The relevant factors explaining the variation of Z_k can, and in general will, be different, depending on how the sampling interval r is chosen. It is shown that if Y_t follows certain dynamic linear models, then the aggregated series can also be described by possibly different DLM. In the examples, the industrial production of Brazil is analysed under various aggregation periods and the results are compared. © 1997 John Wiley & Sons, Ltd.     

Progesterone regulation of implantation-related genes: new insights into the role of oestrogen

Genomic profiling was performed on explants of late proliferative phase human endometrium after 24-h treatment with progesterone (P) or oestradiol and progesterone (17β-E₂+P) and on explants of menstrual phase endometrium treated with 17β-E₂+P. Gene expression was validated with real-time PCR in the samples used for the arrays, in endometrium collected from early and mid-secretory phase endometrium, and in additional experiments performed on new samples collected in the menstrual and late proliferative phase. The results show that late proliferative phase human endometrium is more responsive to progestins than menstrual phase endometrium, that the expression of several genes associated with embryo implantation (i.e. thrombomodulin, monoamine oxidase A, SPARC-like 1) can be induced by P in vitro, and that genes that are fully dependent on the continuous presence of 17β-E₂ during P exposure can be distinguished from those that are P-dependent to a lesser extent. Therefore, 17β-E₂ selectively primes implantation-related genes for the effects of P. H. Dassen, C. Punyadeera: These authors contributed equally. Received 18 December 2006; received after revision 6 February 2007; accepted 8 March 2007     

Specific reaction of aloe extract with serum proteins of various animals

Summary We found that aloe extract contains a lectin-like substance which reacts with serum proteins of various animals. Furthermore, in human serum 2 proteins,a ₂-macroglobulin anda ₁-antitrypsin, were shown to be reactive with aloe extract.