C1 inhibitor hinge region mutations produce dysfunction by different mechanisms.

Heterozygosity for a mutant dysfunctional C1 inhibitor protein, a member of the serine proteinase inhibitor (serpin) superfamily, results in type II hereditary angioneurotic oedema. We identified a "hinge" region mutation in C1 inhibitor with a Val to Glu replacement at P14 Val-432. Recombinant C1 inhibitors P10 Ala-->Thr and P14Val-->Glu did not form stable complexes with fluid phase C1s or kallikrein. The P14 Val-->Glu mutant, however, was cleaved to a 96K form by C1s, while the P10 Ala-->Thr mutant was not. The recombinant P10 mutant also did not complex with C1s, kallikrein or beta-factor Xlla-Sepharose. The two mutations, therefore, result in dysfunction by different mechanisms: in one (P14 Val-->Glu), the inhibitor is converted to a substrate, while in the other (P10 Ala-->Thr), interaction with target protease is blocked.     

Purification of platelet-derived endothelial cell growth inhibitor and its characterization as transforming growth factor-β type 1

In 1986, Brown and Clemmons (Proc. natl Acad. Sci. USA83 (1986) 3321) showed that platelets contain a substance, platelet-derived growth inhibitor (PDGI), that inhibits in vitro endothelial cell replication. Although platelets are rich in transforming grwoth factor (TGF-), PDGI was considered not to be related to TGF-, on the basis of its reported properties (extraction from platelets at neutral pH, binding to heparin-Sepharose). However, we purified PDGI to near homogeneity and showed that on the basis of HPLC retention behavior, in vitro growth inhibitory activities with several cell types, receptor binding, and immunoneutralization of growth inhibitory activity with specific anti-TGF- type 1 antibodies, PDGI is most probably identical with TGF- type 1.     

Evaluation of the hepatotoxicological effects of a drug in an in vivo/in vitro model

Both in vivo and in vitro models have certain disadvantages for the study of the chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new approach based on an in vivo/in vitro model. After chronic in vivo treatment of rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits hepatotoxic properties in man) liver cells were isolated, and functional and metabolic disorders (metabolic utilization of fructose and protein biosynthesis) were studied to determine injury. The results showed no modification of blood parameters, but a direct relationship between the dose of Vindeburnol administered in vivo and the metabolic disorders observed in vitro, evidencing the high sensitivity and reliability of this model.     

Biosynthesis of 1-aminocyclopropanecarboxylic acid: Steric course of the reaction at the C-4 position

Summary Under the action of the appropriate synthase from ripe tomatoes a 11 mixture of (3S, 4R)-[3,4-²H₂] and (3R, 4S)-[3,4-²H₂]-(2S)-adenosylmethionine is transformed into a 11 mixture of the two meso forms of [²H₂]-1-aminocyclopropanecarboxylic acid, a result which proves the operation of an inversion mechanism and which is consistent with direct nucleophilic displacement of the leaving group in the substrate.     

The median procedure for n-trees

Let (X,d) be a metric space The functionM:X ^k 2 ^x defined by is the minimum } is called themedian procedure and has been found useful in various applications involving the notion of consensus Here we present axioms that characterizeM whenX is a certain class of trees (hierarchical classifications), andd is the symmetric difference metricWe would like to thank the referees and Editor for helpful comments     

Molt-induced muscle atrophy decreases the zinc content of the pectoralis of the Giant Canada Goose (Branta canadensis maxima)

Summary During molt-induced atrophy of the pectoralis muscle of the Giant Canada Goose (Branta canadensis maxima), the zinc content of the muscle was significantly reduced (p0.0139), though the concentration of zinc per unit weight of muscle appeared higher (p0.0232). Zinc lost from the muscle during molt could be utilized for growth of the new flight feathers.Acknowledgments. Funds for this study were obtained from an operating grant awarded to J. C. G. by the Natural Sciences and Engineering Research Council of Canada.     

Evolution of the atmosphere and oceans

The residence times of most constituents of the atmosphere and oceans are small fractions of the age of the Earth and, in general, their rate of output has been nearly equal to their rate of input. We are disturbing a number of these dynamic equilibria quite severely. The mineralogy of marine evaporites rules out drastic changes in the composition of sea water during the last 900 Myr. The chemistry of soils formed more than 1,000 Myr ago suggests that the atmosphere then contained significantly more CO2 and less O2 than at present. Hydrogen peroxide may well have been the principal oxidant and formaldehyde the main reductant in rain water between 3,000 and 1,000 Myr ago. Major changes in atmospheric chemistry since that time are almost certainly related to the evolution of the biosphere.     

Secular variation in carbon isotope ratios from Upper Proterozoic successions of Svalbard and East Greenland

Analyses of stratigraphically continuous suites of samples from Upper Proterozoic sedimentary successions of East Greenland, Spitsbergen and Nordaustlandet (Svalbard) provide an approximation to the secular variation in carbon isotope ratios during a geologically and biologically important period of change from around 900 million years ago to the beginning of the Cambrian period. Late Riphean carbonates and organic material show a stratigraphically useful pattern of enrichment in 13C relative to Phanerozoic or earlier Proterozoic samples. Isotopic compositions of isolated samples from other localities are consistent with a worldwide extended interval of enhanced organic burial and consequent net survival of oxidized material, probably O2, just before the initial radiation of metazoans.     

Storage of irradiated human blood; a source of error in quantitative chromosome analysis

Summary Human whole blood was irradiated with 2.5 Gy of 220 kVp X-rays and stored before culture with 9.7 M BrdU and 19.4 or 38.7 M BrdU for 0, 24, 48 and 72 h. The frequency of dicentrics and ring chromosomes was determined in cells staining as first division (M1) metaphases with the fluorescence plus Giemsa technique. Storage had no influence on the observed aberration yields in 44 h cultures containing 9.7 M BrdU. In 66 h cultures at 19.4 M BrdU the observed yields after 2 and 3 days' storage were significantly lower as compared to cultures from fresh blood. No storage effect was revealed in 66 h cultures containing 38.7 M BrdU. In cases where cytogenetic radiation dosimetry has to be carried out using blood samples which have been in transit for 2–3 days, the findings are of relevance for a correct determination of the chromosome damage in M1 cells.     

Determination of certain physical and chemical characteristics of the activating serum factor from preparturient women and women with habitual abortions

Summary Follow-up investigation of the blood sera from preparturient women and women with habitual, abortions showed the presence of a factor which has an activating effect on smooth muscle preparations because it causes the release of prostaglandins. Gel-chromatographic counter flow separation and microelectrophoresis of the blood sera have shown that the isolated serum factor is a water soluble glycopeptide with a molecular weight of about 2000.