Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase with reduced affinity for PP-ribose-P in four related males with gout

Summary A family is described in which four affected males, spanning two generations, have hyperuricemia and gout accompanied by hematuria but are without severe neurologic involvement. The affected males were found to have markedly reduced levels of erythrocytic hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity; these were 5–12% with hypoxanthine and 0.5–3% with guanine as compared to controls. Erythrocytic adenine phosphoribosyltransferase (APRT) was approximately three-fold elevated in the affected individuals.The residual HGPRT activity in affected males enabled characterization of some of the properties of this mutation. The apparent Michaelis constants (km) for both hypoxanthine and guanine were essentially unchanged, whereas the km for PP-ribose-P was approximately 10–20-fold elevated for all four affected males. The enzyme was more sensitive to product inhibition by IMP and GMP than controls, and exhibited greater thermal lability at 65°C than found with control lysates.     

Effect of limited knee-flexion range on peak hip moments of force while transferring from sitting to standing

The hypothesis that limiting the knee-flexion range increases the peak hip-extension moment while transferring from sitting to standing was tested by filming (100 fps) ten normal human volunteers. With the knees flexed 105 degrees from full extension (0 degrees) the mean (+/- 1 S.D.) peak hip-extension moment was 142 (+/- 37) Nm. With the knees flexed only 75 degrees subjects threw their arms and trunks forward to a greater extent, with a peak moment of 253 (+/- 65) Nm (p less than 0.0001). If the peak moments rise to a similar degree in patients with arthritis and limited knee-flexion range, they may accelerate hip joint damage or the loosening of hip endoprostheses.     

Quantification of Intact Cytokinin Glucosides in Datura innoxia Crown Gall Tissue by Desorption Chemical Ionisation Mass Spectrometry

Cytokinin glucosides are routinely quantified as their aglycones produced by enzymic or chemical hydrolysis. It is, however, important to be able to measure their levels per se. The present paper illustrates the use of desorption chemical ionisation mass spectrometry coupled with stable isotope dilution for the determination of intact, underivatized N- and O- glucosyl conjugates of cytokinins in Datura innoxia crown gall tissue. A total of six glucosyl conjugates were determined; the two N-glucosides, zeatin-7-glucoside and zeatin-9-glucoside, were present in higher quantities than the O-glucosyl derivatives of zeatin, dihydrozeatin and their ribosides.     

The influence of foot position on standing balance

To test the hypothesis that variations in foot position would significantly affect standing balance, we studied ten normal subjects on a Kistler force platform which measured the travel and center of pressure displacement. With the feet together there was substantially more mediolateral (ML) travel than with the axes of the feet 15, 30 or 45 cm apart and the mean ML position of the center of pressure was displaced toward the right; there was no consistent effect on anteroposterior (AP) travel or position. As the right foot was placed 10 and 30 cm forward or back, the least amount of ML and AP travel occurred with the feet even or at 10 cm either direction; the mean AP and ML position moved toward the foot which was placed more posteriorly. Of the five foot angles ranging from toes-out 45 degrees to toes-in 45 degrees, the extent of ML and AP travel was lowest in the toes-out 25 degrees position and greatest in the toes-in 45 degrees position; the mean AP and ML position was farthest forward and to the right with toes-in 45 degrees. These findings have implications for the prosthetic replacement of the lower limbs, sports, ergonomics and postural sway studies.     

Enzymic synthesis,chemical characterisation and Sda activity of GalNAcß1-4[NeuAcα2-3]Galß1-4GlcNAc and GalNAcß1-4[NeuAcα2-3]Galß1-4Glc

The tetrasaccharides GalNAcß1-4[NeuAc2-3]Galß1-4Glc and GalNAcß1-4[NeuAc2-3]Galß1-4GlcNAc were synthesised by enzymic transfer of GalNAc from UDP-GalNAc to 3-sialyllactose (NeuAc2-3Galß1-4Glc) and 3-sialyl-N-acetyllactosamine (NeuAc2-3Galß1-4GlcNAc). The structures of the products were established by methylation and¹H-500 MHz NMR spectroscopy. In Sd^a serological tests the product formed with 3-sialyl-N-acetyllactosamine was highly active whereas that formed with 3-sialyllactose had only weak activity.     

Differential efficiency of mutagenesis at three genetic loci in CHO cells by a benzo[a]pyrene diol epoxide

The formation of DNA adducts by the ultimate carcinogen 7r,8t-dihydroxy-9t,10t-oxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene (BPDE-I) has been implicated in the process of carcinogenesis. In a line of Chinese hamster ovary (CHO) cells designated AT3-2 and in two derivative mutant lines, UVL-1 and UVL-10, originally selected for hypersensitivity to UV-irradiation, we have measured the formation of BPDE-I: DNA adducts and the production of biological damage. The quantity and quality of BPDE-I: DNA adducts formed initially in the 3 cell lines are identical over a wide range of BPDE-I doses. However, the UVL lines are unable to remove adducts from their DNA, while the AT3-2 cells remove about 50% of the BPDE-I: DNA adducts in a 24-h incubation. Correlated with this, the UVL lines are more sensitive to the lethal effects of BPDE-I than are the AT3-2 cells. Mutant frequencies were measured at the aprt, hprt and oua loci and were found to increase linearly with BPDE-I: DNA adduct formation at doses which gave greater than 50% survival. At the hprt and oua loci, the efficiency of mutation induction was similar for AT3-2 and UVL-10 cells. UVL-1 cells showed slightly higher (within a factor of 2-3) mutant frequencies in response to BPDE-I compared to AT3-2 at these two loci. However, at the aprt locus the repair-deficient cells were much more highly mutable (9-15-fold) than the repair-proficient AT3-2 cells. Based on the measured average level of adduct formation, it is calculated that 15% of the BPDE-I: DNA adducts in the aprt gene are converted into mutations. However, the possibility exists that the aprt locus is subject to higher levels of modification by BPDE-I than is the bulk DNA, which would lead to an artifactually high apparent conversion frequency.