S-oxalylglutathione is a substrate for gamma-glutamyltransferase (GGT). Implications for the role of GGT in cell proliferation

With glycylglycine or water as acceptor, bovine kidney gamma-glutamyltransferase catalyzes reactions of the known mammalian metabolite, S-oxalylglutathione, at rates comparable to those of L-gamma-glutamyl-p-nitroanilide, a known good substrate. N-Oxalyl-cysteinylglycine is the eventual product of the former reaction. Since oxalyl thiolesters are implicated as important cell proliferation inhibitors, it is proposed that this reaction plays a major role in controlling cell proliferation.     

Maleylated-BSA suppresses IFN-gamma-mediated Ia expression in murine peritoneal macrophages

Maleylated bovine serum albumin (maleyl-BSA) and other polyanionic polymers that are recognized by cell surface receptors on macrophages have been shown to induce chemotaxis, protease secretion, and tumoricidal function in this cell type. In this paper the effect of maleyl-BSA on Ia antigen expression has been evaluated. In a fashion similar to LPS, maleyl-BSA suppressed IFN-gamma-induced expression of Ia in a time- and dose-dependent manner. Also like LPS, maleyl-BSA stimulated the production and secretion of substantial amounts of PGE2 over a 24-hr period. This did not, however, appear to be the primary mechanism by which expression of Ia was suppressed, because co-treatment of the cells with indomethacin, which totally inhibited the production of PGE2, only minimally affected the suppressive activity. Surprisingly, the suppressive activity of both maleyl-BSA and LPS could be largely abrogated by co-treatment of the cells with cyclohexamide during the time period when Ia expression was sensitive to suppression. This effect was selective in that PGE2- or dibutyryl cyclic AMP-induced suppression of Ia expression was not affected by cyclohexamide treatment. The data support the concept that there are multiple molecular mechanisms involved in the negative regulation of IFN-gamma-induced Ia expression in macrophages. Such mechanisms may include, in addition to the synthesis of PGE2 and consequent elevation in intracellular levels of cyclic AMP, one or more proteins made early after treatment with either maleyl-BSA or LPS. Thus the function of some of these early gene products may be to regulate expression of functional genes such as that encoding Ia antigen.     

Determination of oxalyl thiolesters, N-oxalylcysteine and N-oxalylcysteamine in biological materials

A convenient method is described for the quantitative analysis of oxalyl thiolesters (OTEs), a newly discovered class of mammalian metabolites, in biological samples. By this particular technique the total concentration of all OTEs in the sample is determined. The method involves first reacting the biological material with cysteamine (2-aminoethanethiol) or cysteine under conditions that convert OTEs quantitatively to N-oxalylcysteamine (or N-oxalylcysteine), followed by reaction with monobromobimane to give a highly fluorescent derivative that is analyzed by reversed-phase ion-pair chromatography, with tetrabutylammonium ion as the counterion and N-(2-mercaptopropionyl)glycine as an internal standard. The method is capable of detecting as little as 0.6 pmol of the bimane derivative of the N-oxalyl compound in a single HPLC injection. The application of this method has led to the discovery that not only OTEs but also N-oxalylcysteine and N-oxalylcysteamine are normal mammalian metabolites. In various rat tissues the OTE concentration ranges up to 65 nmol/g (wet wt), the N-oxalylcysteine concentration is approximately 10 nmol/g, and the N-oxalylcysteamine concentration is 0-3 nmol/g.     

Experience with Coeliac Axis Compression Syndrome

Seven patients with “coeliac axis compression syndrome” are reported. Five were treated surgically, but only two did well. A survey of 200 healthy adults showed epigastric bruits in 6·5%; only one of these had dyspepsia, though dyspepsia was present in 12·5% overall.Caution is urged in attributing a causal relationship between coeliac axis compression and pain and in proceeding to arteriography when compression is suspected on clinical grounds.     

Anticipatory Smooth Eye Movements in Autism Spectrum Disorder

Smooth pursuit eye movements are important for vision because they maintain the line of sight on targets that move smoothly within the visual field. Smooth pursuit is driven by neural representations of motion, including a surprisingly strong influence of high-level signals representing expected motion. We studied anticipatory smooth eye movements (defined as smooth eye movements in the direction of expected future motion) produced by salient visual cues in a group of high-functioning observers with Autism Spectrum Disorder (ASD), a condition that has been associated with difficulties in either generating predictions, or translating predictions into effective motor commands. Eye movements were recorded while participants pursued the motion of a disc that moved within an outline drawing of an inverted Y-shaped tube. The cue to the motion path was a visual barrier that blocked the untraveled branch (right or left) of the tube. ASD participants showed strong anticipatory smooth eye movements whose velocity was the same as that of a group of neurotypical participants. Anticipatory smooth eye movements appeared on the very first cued trial, indicating that trial-by-trial learning was not responsible for the responses. These results are significant because they show that anticipatory capacities are intact in high-functioning ASD in cases where the cue to the motion path is highly salient and unambiguous. Once the ability to generate anticipatory pursuit is demonstrated, the study of the anticipatory responses with a variety of types of cues provides a window into the perceptual or cognitive processes that underlie the interpretation of events in natural environments or social situations.     

The reduction of alpha-ketocarboxylic acids and alpha-dicarbonyl compounds with titanium(III) chloride

Thirteen model alpha-ketocarboxylic acids and alpha-dicarbonyl compounds have been observed to be reduced by titanium(III) chloride. The products of these reactions were shown by melting (boiling) points, mixed melting points, derivatives, refractive indices, infrared, and NMR comparisons with authentic compounds or literature information to be the corresponding alpha-hydroxycarboxylic acids or alpha-hydroxyketones.     

Electrophoretic analysis of the estrogen receptor. Molybdate stabilization and identification of the classical estrogen receptor

Conditions are defined which permit analysis of estrogen receptors from the mammalian uterus by polyacrylamide gel electrophoresis, thereby solving a longstanding problem encountered in previous attempts at such analysis, namely the failure of a large portion of the receptor population to enter such gels. A paramount requirement for entry of the estrogen-receptor complex into polyacrylamide gels is its maintenance in an untransformed state which does not form aggregates that are excluded from these gels. Of the multiple estrogen-binding proteins separated, only one (relative mobility of 0.5-0.6) possessed the definitive characteristics of the classical estrogen receptor. The inclusion of molybdate in extraction buffers selectively enhanced receptor recovery and facilitated its separation. Moreover, the estrogen-receptor complex so resolved is separated from other types of estrogen-binding proteins present in the uterine cytosol. These findings show that the molybdate-stabilized estrogen receptor exists in a single discrete form, but otherwise exhibits multiple forms that are probably artifactual. Electrophoresis in discontinuous buffers, but not in a continuous buffer system, promoted aggregate formation. This finding has implications concerning the subunit structure of the untransformed receptor.