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R Leff

Publications and source records attributed to R Leff.

6 recordsLinked to original sources
PubMed1994

A motif in human histidyl-tRNA synthetase which is shared among several aminoacyl-tRNA synthetases is a coiled-coil that is essential for enzymatic activity and contains the major autoantigenic epitope.

In myositis, disease-specific autoantibodies may be directed against an aminoacyl-tRNA synthetase, usually histidyl-tRNA synthetase. To explore the basis for this phenomenon, we have made recombinant histidyl-tRNA synthetase in the baculovirus system. It was enzymatically active and recognized by human autoantibodies. A truncated protein lacking the first 60 amino acids was inactive as an antigen and as an enzyme. This region is within the first two exons, is predicted to have a coiled-coil configuration, and is found in some other synthetases but not in Escherichia coli or yeast histidyl-tRNA synthetase. Circular dichroism showed that the peptides from this region (amino acids 1-60 and 1-47) have the predicted high alpha-helical content, but smaller fragments (1-30, 14-45, and 31-60) do not. The peptides with a high alpha-helical content could inhibit autoantibodies almost completely, whereas the smaller peptides were unable to do so. The amino acid sequence of this coiled-coil domain in human histidyl-tRNA synthetase resembles the sequence of the extended this coiled-coil arm near the NH2 terminus of bacterial seryl-tRNA synthetase as well as similar regions in some eukaryotic aminoacyl-tRNA synthetases, raising the possibility that this domain serves a similar tRNA-stabilizing role and has been preserved from a common ancestor.

Amino Acid Sequence↗
PubMed1982

The effects of diazoxide upon fetal and maternal hemodynamics and fetal brain function and metabolism.

The effects of maternal infusion of Diazoxide (D) were evaluated in two groups of experiments: Nine ewes and their five nonhypoxic fetuses; the remaining four fetuses were excluded because of the development of hypoxia prior to the study. D was directly administered intravenously (IV) to the six fetuses. In group 1 maternal and fetal observations were made at 0, 5, 15, 30, and 45 minutes. A 60-minute observation was also made for the maternal infusion studies. Maternal infusion of 5 mg/kg maternal weight significantly reduced maternal pH from the control value at 5 minutes. Maternal metabolic acidosis was indicated by concomitant significant reductions in base deficit (BD) and total bicarbonate (HCO3), both of which remained low for all subsequent time periods. Maternal lactic acid concentration also increased at 15 minutes, although not significantly. Maternal PO2 also fell significantly at 5 minutes, remaining significantly low for the remaining observations. A profound maternal hypotension was elicited at 5 minutes. All following observations for maternal blood pressure (MBP) were also significantly low. Fetal carotid arterial (FCA) pH declined significantly from the control period value at 15 minutes, remaining significantly low for the remaining observations. FCA O2% saturation (O2%) also witnessed a significant decline from baseline for all observations. FCA serum lactate level rose at 15 minutes; however, this was not deemed significant. No significant changes were seen in fetal brain metabolic rate of oxygen or glucose. Fetal electroencephalogram (EEG) revealed a definite hypoxic change in a majority of cases. In group 2, the effects of a direct fetal IV administration of 30 mg D (mean dose = 7.97 mg/kg fetal weight) were studied in six experiments. No significant changes in fetal acid base status or fetal blood pressure (FBP) were witnessed for the 45 minutes under scrutiny. Fetal heart rate (FHR) showed a short transient rise from baseline at 5 and 15 minutes, returning to normal thereafter. A slight significant decrease in O2% saturation and O2 content were seen only for the 5-minute observation. There were no significant changes of fetal brain function and metabolism observed following D administration to the fetus. The significant fetal hypoxia and acidosis witnessed through the maternal infusion but not in the direct fetal bolus administration were probably owing to profound maternal hypotension resulting in deterioration of uteroplacental perfusion and fetal "gas exchange."

Animals↗