Control of Oxidative Damage in Rheumatoid Arthritis By Gold(I)-Thiolate Drugs

The roles of anti-arthritic gold(I)-thiolate drugs such as disodium aurothiomalate ('Myocrisin') in the modulation or promotion of oxygen radical-mediated oxidative damage in vivo ate reviewed. In particular, the precise molecular mechanisms by which these novel second-line agents exert their therapeutic effects are discussed in terms of (i) the direct and indirect control of enzymes involved in the generation or scavenging of reactive oxygen speices (ROS) such as superoxide ion, hydrogen peroxide and hydroxyl radical, (ii) the protection of proteins and relevant enzyme systems against attack by ROS and (iii) their direct involvement in the production (at appropriate 'target' sites) or scavenging of ROS in vivo. In addition, the role of the orally-effective gold(I)-phosphine complex auranofin in the control of oxidative damage in rheumatoid arthritis is also discussed.     

Synthesis of enantiomeric pureCis-dichloroplatinum(II) amino acid complexes

The reaction of potassium tetrachloroplatinate(II) with six representative sulfurcontaining amino acids, namely,d- andl-cysteine,d- andl-methionine and its methyl ester hydrochloride gives the corresponding enantiomerically purecis-dichloroplatinum(II) complexes. This represents the first reported series of well-characterized enantiomerically pure platinum(II) complexes for bothd- andl-amino acids. The spectroscopic properties, including IR,¹H-NMR, and¹³C NMR, of these complexes and their configuration are discussed.     

The temporal order of replication of murine immunoglobulin heavy chain constant region sequences corresponds to their linear order in the genome.

The time of replication during the S phase in a murine erythroleukemia (MEL) cell line was determined for immunoglobulin heavy chain constant region C alpha, C gamma 2b and C mu sequences whose boundaries are defined by EcoR1 restriction endonuclease sites (EcoR1 segments). Logarithmically growing cultures of MEL cells with an S phase of about 7.5 hours were pulse labelled with 20 micrograms/ml of 5-bromodeoxyuridine (BUdR). The cells were then fractionated by centrifugal elutriation into 10-12 distinct populations containing cells in different stages of the cell cycle. Flow microfluorimetric (FMF) analysis of DNA content, measurements of cell volume and autoradiography after 3H-thymidine pulse labelling were used to determine position in the cell cycle. Fractions were pooled to represent four selected intervals of S in which BU-DNA was synthesized for 2.5 hrs or less. Newly replicated DNA which had incorporated BUdR into one strand was isolated, cleaved with EcoR1, and separated on neutral Cs2S04 gradients. Equal amounts of BU-DNA replicated during these four intervals of S were electrophoresed in 0.8% agarose gels, transferred to diazotized aminobenzyloxymethyl paper and hybridized with 32p probes containing the C alpha, C gamma 2b and C mu genes and flanking sequences. The relative amounts of segments replicated were assessed by quantitation of the appropriate bands on the autoradiograms by microdensitometry. The results indicate that the 2.8 kb C alpha, 6.6 kb C gamma 2b and 12 kb C mu EcoR1 segments in these MEL cells replicated during defined intervals of the first half of the S phase. The order of replication of these EcoR1 segments as the cells proceeded through S was C alpha, C gamma 2b, C mu, corresponding to the linear order of the genes determined by restriction endonuclease mapping.     

Induction of peroxisome proliferation and increase of catalase activity in yeast,Candida albicans,by cadmium

The effects of cadmium on the growth rate, catalase activity, and peroxisome proliferation in yeast,Candida albicans, were evaluated. The yeast growth was markedly inhibited by 1 mM cadmium at the initial hours. The toxic effect of cadmium on the cell growth persisted. The catalase activity of the cells treated with 1 mM Cd²⁺ first decreased, and then rose at 24 h to about 2.6 times that of the controls. The average number of peroxisomes per cell in the yeast treated with 1 mM Cd²⁺ was about sixfold higher than the control groups. The proliferation of peroxisomes and the increase of catalase activity following cadmium toxicity gives credence to the hypothesis that cadmium toxicity is related to its potential to induce oxidative stress in cells.     

Preparation of NG-monoethyl-l-arginine

N^G-Monoethyl-l-arginine, a putative in vivo product after administration of the potent hepatocarcinogen l-ethionine to rats, has been chemically synthesized by coupling N-ethyl, S-methylthiopseudouronium iodide with α-amino-blocked l-ornithine. The structure of the compound as N^G-monoethyl-l-arginine was confirmed by ¹³C NMR. Its elution time on an automatic amino acid analyzer, R_f values using thin-layer chromatography, and isoelectric point have been compared with those of N^G-monomethyl-l-arginine.     

An evaluation of D-glucosamine as a gratuitous catabolite repressor of Saccharomyces carlsbergensis

Molecular Genetics and Genomics - Glucose represses mitochondrial biogenesis and the fermentation of maltose, galactose and sucrose in yeast. We have analyzed the effect of D-glucosamine on these...     

Electron cryomicroscopy structure of N-ethyl maleimide sensitive factor at 11 A resolution

N-ethyl maleimide sensitive factor (NSF) belongs to the AAA family of ATPases and is involved in a number of cellular functions, including vesicle fusion and trafficking of membrane proteins. We present the three-dimensional structure of the hydrolysis mutant E329Q of NSF complexed with an ATP-ADP mixture at 11 A resolution by electron cryomicroscopy and single-particle averaging of NSF.alpha-SNAP.SNARE complexes. The NSF domains D1 and D2 form hexameric rings that are arranged in a double-layered barrel. Our structure is more consistent with an antiparallel orientation of the two rings rather than a parallel one. The crystal structure of the D2 domain of NSF was docked into the EM density map and shows good agreement, including details at the secondary structural level. Six protrusions corresponding to the N domain of NSF (NSF-N) emerge from the sides of the D1 domain ring. The density corresponding to alpha-SNAP and SNAREs is located on the 6-fold axis of the structure, near the NSF-N domains. The density of the N domain is weak, suggesting conformational variability in this part of NSF.