Comparison of the inhibition of avian and mammalian bone alkaline phosphatases by levamisole and compound R8231

Summary Alkaline phosphatases from mammalian bone are inhibited much more than chick bone alkaline phosphatase by levamisole and compound R8231. Doses of R8231 (10^–4 to 10^–5 M) that almost completely inhibit mammalian alkaline phosphatases do not inhibit the growth of embryonic rat femurs in vitro. R8231 should be an excellent biological probe for the function of alkaline phosphatase in bone metabolism.Acknowledgments. This work has been supported by funds from the Medical Research Council.     

Biochemical compartmentation of fish tissues. II. Nonspecific phosphomonoesterases in brain.

The specific activities of acid and alkaline phosphatases in different regions of the brain of 9 nutritionally important fishes were worked out. The region consisting of pituitary, hypothalamus and thalamus showed the highest acid and alkaline phosphatase activities. Least activities of both the enzymes were found in the cerebellum and medulla oblongata. The piscivorous fishes contain the highest acid and alkaline phosphatase activity followed by cat fishes and major carps. The distributional pattern of these 2 enzymes in 4 regions of the brain of 9 fishes is the same.     

Dissociation-constants of metal-ion-complexes with alkaline phosphatase from pig kidney

Summary Using metal-ion buffers it was possible to remove Zn²⁺, Mg²⁺ and Mn²⁺ ions of pig kidney alkaline phosphatase reversibly. The dissociation constants obtained are K_EMg:4·10^–7 M, K_EMn:4·10^–8 M and K_EZn:8·10^–13 M (22°C, pH:9.6, :0.07).Acknowledgement: The authors thank Dr.H. U. Wolf for helpful suggestions and valuable discussion and MissH. Köth for technical assistance.     

9,10-Dihydroergotamine: Production of antibodies and radioimmunoassay

Summary Antibodies against 9,10-dihydroergotamine (DHE) were produced by immunizing rabbits with a conjugate of 6-nor-6-carboxymethyl-9,10-dihydroergotamine and bovine serum albumin. A highly specific and sensitive radioimmunoassay for DHE has been developed.We are greatly indebted to Dr.T. Fehr for the synthesis of 6-nor-6-carboxymethyl-9,10-dihydroergotamine, and to Dr.E. Schreier for providing us with 9,10-dihydroergotamine-[13-³H]-base of high specific activity.     

The influence of ingested fluoride on the ascorbic acid concentration in guinea-pig tissues

Summary Fluoride added to drinking water at concentrations of 50 and 70 ppm provided highly significant increases in the ascorbic acid concentration in tissues but was without effect on the serum alkaline phosphatase and cholesterol.JEWD was supported by a Beecham Products grant.     

Tyrosine phosphatase activity in mitochondria: presence of Shp-2 phosphatase in mitochondria

Tyrosine phosphorylation by unidentified enzymes has been observed in mitochondria, with recent evidence indicating that non-receptorial tyrosine kinases belonging to the Src family, which represent key players in several transduction pathways, are constitutively present in mitochondria. The extent of protein phosphorylation reflects a coordination balance between the activities of specific kinases and phophatases. The present study demonstrates that purified rat brain mitochondria possess endogenous tyrosine phosphatase activity. Mitochondrial phosphatases were found to be capable of dephosphorylating different exogenous substrates, including paranitrophenylphosphate, ³²P-poly(Glu-Tyr)_4:1 and ³²P-angiotensin. These activities are strongly inhibited by peroxovanadate, a well-known inhibitor of tyrosine phosphatases, but not by inhibitors of alkali or Ser/Thr phosphatases, and mainly take place in the intermembrane space and outer mitochondrial membrane. Using a combination of approaches, we identified the tyrosine phosphatase Shp-2 in mitochondria. Shp-2 plays a crucial role in a number of intracellular signalling cascades and is probably involved in several human diseases. It thus represents the first tyrosine phosphatase shown to be present in mitochondria.Received 17 May 2004; received after revision 20 July 2004; accepted 26 July 2004     

Acid and alkaline phosphatase heterogeneity in liver,heart and intestine of the adult chick

Summary The molecular heterogeneity of acid and alkaline phosphatase from chick liver, intestine and heart is demonstrated by polyacrilamide disc gel electrophoresis. Liver and heart show the same number of molecular forms of acid and alkaline phosphatases. In contrast, the intestine homogenate shows electrophoretic bands different in number and in gel position from those of the liver and of the heart.     

Wirkung der Glutaminsäure auf die experimentelle Isoniazid-Schädigung peripherer Nerven bei Ratten

Summary Glutamic acid does not, either in small or in large doses, inhibit the degeneration of the medullary sheath of peripheral nerves in rats, induced within 15 days by addition of 0.25% of isoniazid to their diet. The detoxicating effect of glutamic acid, as described byCedrangolo ¹, thus only applies to the general toxic symptoms of the acute INH-intoxication, as is the case for vitamins B₂, B₁₂, A, E, K, and niacinamide.     

Agglutininbildung durch verschiedene Proteinfraktionen vonSalmonella ballerup

Summary The author has examined the agglutinogenic property of nucleoprotein and its components, the nucleic acid and proteins fromS. ballerup. The nucleoprotein was obtained by the extraction of fresh bacteria desintegrated by means of glass powder at pH 8.4 and precipitated with acetic acid at pH 4.6, and its components by splitting the nucleoprotein with 0.5% sodium carbonate at pH 5.5. The protein component was separated from the nucleic acid by forming a chloroform-proteingel. The protein component was submitted to a further purification by dissolving at pH 7 and precipitating at pH 5.5. Rabbits to whom 4–8 mg of the substance were given in 10–12 doses were used for the immunization. The agglutinins were determined byHeidelberger andKabat's quantitative method with aS. ballerup suspension. The maximum quantity of agglutinin is shown in mg nitrogen per 1 cm³ of serum. In comparison with the results obtained by the immunization with whole germs, it follows that, by means of nitrogen compounds, the nucleoprotein has the most substantial agglutinogenic effect, and the nucleic acid the poorest one.     

Comportamento delle fosfatasi alcaline all'azione di alcuni veleni carioclasici

Summary The effect of an aqueous solution (6 · 10^–3 M) of mustard oil on phosphatases was tested in cymotoid oocytes by treatment either of fixed and sectioned ovaries or of fresh gonads. Nuclear and cytoplasmic mono- and diphosphatases are destroyed; nucleolar phosphatases on the contrary are unaltered or only slightly damaged.The authors put forward the hypothesis that nucleolar phosphatases have a different kind of enzymatic active groups which might have a low competition factor in regard to mustard oil. Possibly the caryoclasic action of this substance is due, at least in part, to the destruction of alkaline phosphatases which are necessary to mitotic processes.     

Bacterial endotoxin and impaired fetal development

Summary Small doses ofE. coli endotoxin given to pregnant mice on the 13th day of pregnancy caused only a mild maternal illness but induced resorption of approximately half the number of fetuses in each mouse. The remaining live fetuses developed normally and showed no evidence of retarded growth or malformations. The weights of their placentas and maternal spleens increased significantly. Endotoxin given on the 6th day of pregnancy caused a small reduction in fetal weights.Acknowledgments. I am indebted to Mrs.Heather Sandison for technical assistance and to Mr.M. J. R. Healy for statistical examination of the results. Dr.A. B. G. Lansdown kindly advized on the interpretation of histological findings.     

Phosphoprotein phosphatase activity of bovine intestinal alkaline phosphatase

The phosphoprotein phosphatase activity of a commercial preparation of bovine intestinal alkaline phosphatase (EC 3.1.3.1) was examined using phosvitin and dentine phosphoprotein as substrates. Over 90% and 70% of the phosphorus from dentine phosphoprotein and phosvitin were hydrolyzed in 2 h. The optimum pH of the enzyme for the dephosphorylation of phosvitin and dentine phosphoprotein was nearly 6. No protein phosphatase activity was observed when the alkaline phosphatases from bovine liver and pulp were investigated.     

Xanthindehydrogenase beim Wildtyp und bei den Mutantenwhite andbrown vonDrosophila melanogaster

Summary Mature larvae, one day and three days old pupae, one day and ten days old adultDrosophila melanogaster males were assayedin vitro for the enzyme, xanthinedehydrogenase. Very high enzyme activity was found in wildtype and bothw andbw throughout the period investigated. Also 6 days oldwhite flies proved to be able to form isoxanthopterin from 2-amino-4-oxypteridine in anin vivo assay. The results are discussed with regard to the absence of isoxanthopterin and uric acid inwhite andbrown imagines.

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Ausgeführt mit Unterstützung des Schweiz. Nationalfonds zur Förderung der wissenschaftlichen Forschung. Herrn Prof. Dr.E. Hadorn danke ich herzlich für die Förderung dieser Arbeit.     

Zeitbedarf der Längsteilung von miteinander verzwirnten Fadenmolekülen

Summary The time requirement is treated for a longitudinal fission by Brownian movement of a very long particle consisting of two or more filaments twisted a great number of times round each other to form a double spiral. It is shown that a comparatively swift disintegration is obtained by partial rotation or torsion round the axis of the spiral, resulting in a loosing of the spiral structure and subsequent separation of the constituents by translational Brownian movement. The time required to separate a double spiral consisting of about 900 turns of a height of 3.4 × 10⁻⁷ cm and a radius of 10⁻⁷ cm, thus having a length of 3 × 10⁻⁴ cm being realized approximately by deoxyribonucleic acid is found by this mechanism to be about 50 to 80 s. The time required to undo the same spiral by unwrapping it turn by turn would be about 150 days. The result of the considerations is related to observations published byAlexander andSteacy on deoxyribonucleic acid. An additional remark stresses the importance of stereochemical asymmetry for the practicability of the mechanism and therefore the importance of optical activity for the time requirement of such disintegrations or transformations of high polymer material occurring in living organisms.      

Die alkalische Phosphatase-Aktivität des Ratten-serums nach anaphylaktoidem Schock

Summary At seven different intervals after the elicitation of anaphylactoid shock (compound 48/80), determinations of alkaline phosphatase (AP) activity were carried out in rat serum. No significant increase could be detected. These findings exclude extrarenal factors as the cause for increased AP-activity in urine following anaphylactoid shock.     

Bestimmung der Transferrintypen bei Rindern durch vertikale Polyacrylamidgel-Elektrophorese

Summary 997 samples of cattle serum were separated by means of polyacrylamidgelelectrophoresis and the frequency of transferrin phenotypes were determined. The electrophoresis was carried out in outfit for vertical gel electrophoresis according toRaymond ². For better resolution of proteins 2 gels of different density were used for separation. The method offers the possibility to compare the samples directly.     

Der Sauerstoffumsatz der Leber von Ratten während der Höhenakklimatisation

Summary The O₂-consumption of liver tissue of male rats of different ages during the first 10 days at an altitude of 3540 m was significantly decreased on the 5th and 7th day. The deviation from the controls at ground level was – 19% in 40-day-old and – 30% in 11-month-old male rats.

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Auslandsstipendiat der Schweizerischen Regierung (1963–64). Für die Überlassung eines Laboratoriums und der Apparate möchte ich Herrn Prof.A. v. Muralt auch an dieser Stelle danken.

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Die Arbeit wurde unterstützt von der Max-Planck-Gesellschaft zur Förderung der Wissenschaften, Deutschland. Ein Teil der Versuchstiere wurde uns freundlicherweise von der Hoffmann-La Roche AG, Basel, durch Herrn Dr.Loosli, Füllinsdorf (BL) zur Verfügung gestellt.     

Development of thermoregulation in the newborn lesser bushbaby (Galago senegalensis moholi,Smith 1839)

Summary The temperature-regulating system in bushbabies operates from the 1st day of life. The postnatal metabolism decreases from the 5th (2.9 ml O₂/g·h) to the 140th day (0.7 ml O₂/g·h) to the level of the adults.This work was undertaken with the aid of the Deutsche Forschungsgemeinschaft and Prof. Dr. E.Kulzer.     

Diaquo-bis-(N-2-picolyloxamidato)-kobalt(II), eine Modellverbindung für die Struktur des Aktivzentrums einer alkalischen Phosphatase ?

Summary N-(2-picolyl)-oxamide, N,N-dimethyl-N-(2-picolyl)-oxamide and N-(2-picolyl)-oxamic acid form green Co(II)-complexes with an unfamiliar type of absorption spectrum. A similar spectrum is found, when Zn²⁺ in alcaline phosphatase is replaced by Co²⁺ via isomorphous substitution and it is suggested that the micro environments of the central atoms in both complexes are closely related. Possible structures of the complexes are discussed.

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Herrn Dr.Elschenbroich (Institut für Physikalische Chemie der Universität Basel) und Herrn Dr. E.König (Universität Erlangen) danken wir für die Aufnahme der ESR-Spektren bzw. die Durchführung der magnetischen Messungen.

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Die vorliegende Untersuchung ist ein Teil der vom Schweizerischen Nationalfonds zur Förderung der wissenschaftlichen Forschung unterstützten Projekte Nr. 4689.2 und 5035.2.     

Distribuzione di fosfatasi alcaline in gonadi di Crostacei isopodi in rapporto al ciclo degli acidi nucleici

Summary The distribution of alkaline phosphatases has been studied in male and female gonads of some isopod crustaceans by means of Gomori's reaction.Monophosphatases are found on all Feulgen-positive nuclear structures, in the nucleolus and in the cytoplasm of young oocytes. They disappear from the cytoplasm in auxocytosis, during yolk formation, although they persist in the germinal vesicle. The authors think that the cytoplasmic localization is coincident with ribonucleic acid distribution.From the experiments related in the following note, nucleolar phosphatases appear to be in some way different from the nuclear (sensu stricto) and cytoplasmic phosphatases.Diphosphatases do not follow so closely the nucleic acid localization. They are absent from cytoplasm; in the nucleolus they are not distributed uniformly but show characteristic structure; in the nucleus they are not localized in the chromosomes but homogeneously diffused.