Structure of Cu2(indomethacin)4 and the reaction with superoxide in aprotic systems

The copper complex of indomethacin (1-(p-chlorobenzoyl)-5-methoxy-2-methyl-indole acetate), a common anti-inflammatory drug, was prepared and characterized. Crystal structure determination revealed the dimeric form of the 1:2 complex, namely Cu₂(indomethacin)₄ · L₂, in the unit cell. Suprisingly, the copper-copper distance (263 pm) was very close to metallic copper (256 pm). The two coordination sites in the copper-copper axis can be readily replaced by superoxide. An intriguing similarity to Cu₂(acetate)₄ was seen.Due to the lipophilic nature of the indomethacin ligand, this copper complex reacted with superoxide in aprotic solvents. The superoxide dismutating activity was successfully demonstrated in Me₂SO/water and acetonitrile/water mixtures using the nitro-blue tetrazolium assay and pulse radiolysis. The second-order rate constant of 6 · 10⁹ M^?1 · s^?1 in strictly aqueous systems dropped only slightly to 1.1 · 10⁹ M^?1 · s^?1 when aprotic solvents were used. This is the fastest rate constant ever observed for a copper-dependent dismutation of superoxide. The KO₂-induced lipid peroxidation in both erythrocytes and liver microsomes was suppressed by 70% in the presence of 1 · 10^?10 mol · ml^?1 of Cu₂(indomethacin)₄. The inhibitory action dropped to 25% when Cu₂Zn₂superoxide dismutase was employed. The formation of copper · indomethacin in rat serum after administration of indomethacin was shown in vitro and in vivo.     

A novel role for interleukin 2 in antibody responses: down-regulation of T helper cell activation

This report provides new insights into the role of the T cell growth factor interleukin 2 (IL 2) for the regulation of antibody responses. Evidence is presented that IL 2 down-regulates T helper cell (Thc) activation but not Thc effector function, i.e., Thc-B cooperation. Thus, reagents which block the IL 2 pathway, e.g., cyclosporin A (CsA) or IL 2 receptor monoclonal antibodies (IL 2R Mab) enhanced Thc activation although T cell proliferation was blocked. In contrast, CsA or IL 2R Mab blocked Thc-B cooperation, suggesting that IL 2 is required for this step. The regulatory role of IL 2 was reconfirmed by the addition of exogenous IL 2 into the cultures which reversed the enhancing or blocking effect of CsA.     

SOS Chromotest study concerning some appreciation criteria of humic substances' genotoxic potency

The genotoxicity of 5 compounds: 2 fulvic acids, a trade humic acid, a synthetic humic material (SHM), and 2,5-dihydroxybenzoic acid, was assessed after chlorination, by means of the SOS Chromotest for tester strain E. coli PQ 37 without metabolic activation. Chlorination was carried out for humic material concentration of 0.5 mg total organic carbon per liter, and chlorine concentrations in the range of 0.1-2.0 chlorine equivalents per mole of carbon. Among all the considered criteria that can account for potent toxicity: chemical degradation determined by the UV absorption decrease, chlorine consumption, average molecular weight, only the polymerization index (O.D. 665 nm/O.D. 465 nm) can be related to the genotoxicity of humic samples. This latter criterion appears a possible predictor of genotoxic potency, revealed subsequent to the aqueous chlorination of humic materials. Looking at the various genotoxic activities of the tested compounds, SHM can be considered a better model of natural humic materials than the trade humic acid.     

Changes in the auditory system of locusts (Locusta migratoria and Schistocerca gregaria) after deafferentation

Deafferentation experiments during postembryonic development show morphological and/or physiological changes of receptor fibers and of identified auditory interneurons in the CNS of the locusts Locusta migratoria and Schistocerca gregaria after unilateral ablation of one tympanic organ either in the larva or the adult animal.

Assignment of the gene encoding the catalytic subunit Cβ of CAMP-dependent protein kinase to the p36 band on chromosome

Summary A cDNA for the human catalytic subunit (C) of cAMP-dependent protein kinase (PKA) has been cloned from a testis cDNA library. In the present study, we have determined the chromosomal localization of this gene using a cDNA for C as a probe. Southern blot analysis of genomic DNA from human/mouse cell hybrids revealed that the presence or absence of a 20-kbXbaI fragment, which hybridized with the C probe, was concordant with the presence of human chromosome 1.In situ hybridization to metaphase chromosome confirmed the somatic cell hybrid data and regionally mapped the C gene of PKA to the p36 band on chromosome 1.     

Isolation and regional localization of a large collection (2,000) of single-copy DNA fragments on human chromosome 3 for mapping and cloning tumor suppressor genes

Summary A collection of 2,000 lambda phage-carrying human single-copy inserts (> 700 bp) were isolated from two chromosome-3 flow-sorted libraries. The single-copy DNA fragments were first sorted into 3p and 3q locations and about 700 3p fragments were regionally mapped using a deletion mapping panel comprised of two humanhamster and two-human-mouse cell hybrids, each containing a chromosome 3 with different deletions in the short arm. The hybrids were extensively mapped with a set of standard 3p markers physically localized or ordered by linkage. The deletion mapping panel divided the short arm into five distinct subregions (A-E). The 3p fragments were distributed on 3p regions as follows: region A, 26%; B, 31%; C, 4%; D, 4% and E, 35%. We screened 300 single-copy DNA fragments from the distal part of 3p (regions A and B) with ten restriction endonucleases for their ability to detect restriction fragment length polymorphisms (RFLPs). Of these fragments 110 (36%) were found to detect useful RFLPs: 35% detected polymorphisms with frequency of heterozygosity of 40% or higher, and 25% with frequency of 30% or higher. All polymorphisms originated from single loci and most of them were of the base pair substitution type. These RFLP markers make it possible to construct a fine linkage map that will span the distal part of chromosome 3p and encompasses the von Hippel-Lindau disease locus. The large number of single-copy fragments (2,000) spaced every 100–150 kb on chromosome 3 will make a significant contribution to mapping and sequencing the entire chromosome 3. The 300 conserved chromosome 3 probes will increase the existing knowledge of man-mouse homologies.     

Seasonal variation in catabolic enzyme activities in breast muscle of some migratory birds

Summary Five bird species were examined in order to ascertain if any changes in flight muscle catabolism take place between breeding season and migration. Two different patterns were discovered. The first consists of a high oxidative capacity and a low glycolytic and anaerobic capacity during migration. The converse occurs during the breeding season, i.e. low oxidative, high glycolytic and anaerobic capacity. The pattern was found in those species that deposit large amounts of fat prior to migration. The second pattern was similar to the first, but there was no change in fatty acid oxidation capacity between breeding season and migration. The pattern was found in those species that do not deposit much fat towards migration. These changes are believed to reflect differences in migration strategy and differences in locomotory activity during different seasons. Deviations from these patterns are discussed.     

Isolation and characterization of a new thermophilic and autotrophic methane producing bacterium:Methanobacterium thermoaggregans spec. nov.

Methanobacterium thermoaggregans is a new thermophilic autotrophic rod-shaped methane producing bacterium. The organism likes to form aggregates during growth and utilizes only H₂ and CO₂ as substrates. Growth optimum is at 65°C with a doubling time of 3.5 h. Optimal growth occurs at pH-values between 7 and 7.5. The addition of yeast extract to the mineral salt medium stimulates growth. The DNA base composition is 42 mol% G+C. The organism was isolated from mud taken from a cattle pasture. Because of its optimal growth temperature and its tendency to form aggregates the nameMethanobacterium thermoaggregans is suggested.Abbreviations G+C Guanine+cytosine     

Duration of retained fetal membranes and subsequent fertility in dairy cows

Lactations from 1,111 heifers and 2,493 cows were evaluated for the effects of the duration of retained fetal membranes on subsequent fertility. Cows or heifers with metritis, ovarian cyst, both metritis and cyst, or neither were evaluated in separate strata in order to control for the effects of parity, metritis, and cyst on fertility. Duration of retention had no effect on fertility if an animal had metritis or cyst. There was a suggestion that retained fetal membranes in heifers free of metritis and cyst decreased conception rate at first service. In multiparous cows free of metritis and cyst there was a significant decrease in conception rate at first service when retention exceeded 5 days, and delays of +18 days to 1st service and +57 days to conception when retention exceeded 7 days.