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.     

A frameshift mutation in the gamma E-crystallin gene of the Elo mouse.

The murine Elo (eye lens obsolescence) mutation confers a dominant phenotype characterized by malformation of the eye lens. The mutation maps to chromosome 1, in close proximity to the gamma E-crystallin gene which is the 3'-most member of the gamma-crystallin gene cluster. We have analysed the sequence of this gene from the Elo mouse and identified a single nucleotide deletion which destroys the fourth and last "Greek key" motif of the protein. This mutation is tightly associated with the phenotype, as no recombination was detected in 274 meioses. In addition, the mutant mRNA is present in the affected lens, providing further support for our hypothesis that the deletion is responsible for the dominant Elo phenotype.     

Determination of erythrocyte pyrimidine 5′-nucleotidase activity by31P nuclear magnetic resonance: Comparison of normal controls and multiple sclerosis patients

Summary A technique to assay erythrocyte pyrimidine 5-nucleotidase activity in situ using³¹P nuclear magnetic resonance spectroscopy is presented. The assay is chemically specific, simple and applicable to untreated lysates. A comparison of enzyme levels in normal controls and in multiple sclerosis patients employing the assay yielded no significant differences between both groups. Difficulties encountered in the quantitative analysis of the assay using¹H-NMR spectroscopy are briefly discussed.     

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.     

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.     

Suitability of urethane anesthesia for physiopharmacological investigations in various systems Part 1: General considerations

Summary The suitability of urethane anesthesia for physiopharmacological investigations is reviewed. Total dose administered and route of administration are recognized as factors having a great influence on both resting parameters and biological responses to drugs. A peculiar characteristic of urethane is represented by its ability to induce a surgical plane of anesthesia without affecting neurotransmission in various subcortical areas and the peripheral nervous system. This makes urethane a suitable general anesthetic for studying neural function in both central and peripheral nervous systems and accounts for the preservation of a number of reflex responses in urethane-anesthetized animals.     

Novel rearrangement of purines

6-Trichloromethyl-9-methylpurine (1) rearranges to 6-dichloromethyl-9-methyl-8-oxopurine (2) in aqueous mild acidic solution. The rearrangement is rationalized in terms of a reaction involving protonation, covalent hydration, prototropic equilibrium and/or a hydride transfer. An alternative mechanism involving a "positive' halogen compound and hypochlorous acid as an intermediary is also proposed. Compound 1 condenses with 4,5-diaminopyrimidine to give the purine-pyrimidine Schiff base pair 4.     

Juvenile hormone titre and regulation in the cockroachDiploptera punctata

Summary Titres of juvenile hormone (JH) have been determined in both hemolymph and whole body extracts of femaleDiploptera punctata during the first gonotrophic cycle using a method employing gas chromatography/mass spectrometry for qualitative and quantitative analysis. JH III is the sole JH found in both adult and last instarD. punctata. Maximum values of 1500 ng/ml (6M) were observed at the middle of the gonotrophic cycle, when basal oocyte growth rate was greatest. Changes in rates of JH release in vitro by corpora allata paralleled closely the changes in JH titre, suggesting that biosynthesis is a major regulator of titre. JH levels per animal were calculated from observed JH titres, and at certain time points in the gonotrophic cycle JH levels obtained from analysis of whole bodies were significantly greater than those predicted from hemolymph titres. These results suggest the existence of a nonhemolymph JH pool inD. punctata. Decay in JH titre after allatectomy of 5 day females has also been studied. Following a rapid initial decline, the rate of decay slowed appreciably 4 h post-operation. Thus, use of a first-order rate constant to estimate half-life of JH significantly underestimated the longevity of the hormone. The apparent persistence of JH following allatectomy may be due to the existence of a nonhemolymph JH pool.     

Endorcine cells producing regulatory peptides

Summary Recent data on the immunologication of regulatory peptides and related propeptide sequences in endocrine cells and tumours of the gastrointestinal tract pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory beenrevised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptidesare the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, -MSH and CLIP (corticotropoin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenalin-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.     

Perennial N2 supersaturation in an Antarctic lake

The dry valleys of southern Victoria Land in Antarctica contain several closed basins in which perennially ice-covered lakes are found. One of the most unusual features of these lakes is the occurrence of high O2 concentrations in the water column; values ranging from slightly more than saturation to more than four times saturation have been reported. Recently, we considered a bulk O2 budget for Lake Hoare, Antarctica, which led us to suggest that biological processes alone were not sufficient to explain the observed elevated oxygen levels. Consequently, there must be a non-biological source of O2. We suggested that this source results from the exclusion of O2 during the freezing of aerated meltstream water at the bottom of the ice cover, and predicted that this physical mechanism should also enhance the other atmospheric gases. Here we report the results of a study which, for the first time, documents the supersaturation of N2 in a lake. Dissolved N2 levels of 145% and 163% were determined from samples taken just below the ice cover and at a depth of 12 m, respectively. The relatively importance of biological and abiological sources is reflected in the ratio of N2 concentration to O2 concentration. In Lake Hoare this ratio was 1.20 at ice/water interface and 1.05 at 12 m; considerably different from the ratio in equilibrium with air (approximately 1.8). Based on these results, we have determined that about half of the net O2 production in the lake is the result of biological processes.