When a human being is placed for several days on a completely defined diet, consisting almost entirely of small molecules that are absorbed from the stomach into the blood, intestinal flora disappear because of lack of nutrition. By this technique, the composition of body fluids can be made constant (standard deviation about 10%) after a few days, permitting significant quantitative analyses to be performed. A method of temperature-programmed gas-liquid partition chromatography has been developed for this purpose. It permits the quantitative determination of about 250 substances in a sample of breath, and of about 280 substances in a sample of urine vapor. The technique should be useful in the application of the principles of orthomolecular medicine.

Abstract. Experiments on model peptides show that the rate of deamidation of asparaginyl residues depends strongly on the nature of neighboring residues. The natural distribution of glutaminyl and asparaginyl residues is ordered with respect to the biological lifetime of the peptides and the functional groups of the residues neighboring to glutaminyl and asparaginyl residues. The rates of deamidation of such amide peptides under physiological conditions could serve as useful timers of development and aging.The instability of the amino acids glutamine and asparagine with respect to hydrolytic deamidation of their functional side chains under relatively mild chemical conditions is well known. [1][2][3][4] The instability of glutaminyl and asparaginyl residues is a hazard during purification and primary structure determinations of peptides and proteins. In addition, now that Merrifield's solidphase peptide synthesis5-726 procedure has made the synthesis of peptides easily available to all laboratories, it seems likely that the differential stabilities of amide side chains during synthetic procedures will provide an additional problem.The experiments of T. Flatmark8-10'27 on the properties of the deamidated forms of horse heart cytochrome c show that variations occur in the rate of deamidation of different amides in the same protein molecule and that the deamidated cytochromes exhibit altered biological activity and structure. Deamidation has also been observed in numerous other proteins.11Why are these potentially unstable residues so widely distributed in nature? We suggest that controlled deamidation of glutaminyl and asparaginyl residues is a mechanism by which molecular and organismic development and aging are controlled.The rates of deamidation of glutaminyl and asparaginyl residues in proteins are probably determined by the primary and tertiary structures that govern distribution of amino acid residues surrounding the glutaminyl and asparaginyl residues in proteins. We have undertaken a study of the primary sequence dependence of deamidation of glutaminyl and asparaginyl residues in l)eptides.By comparing our results with the rates of deamidation of peptides of natural sequences and their corresponding proteins, we should also be able to make estimates of the tertiary structure dependence of deamidation. The results of our MAierrifield syntheses of the needed model peptides should aid in the prediction of difficulties during peptide synthesis and purification.

No abstract

No abstract

A case of fetal demise and maternal recovery after acetaminophen overdose is presented, to our knowledge the first reported. Fetal liver and maternal serum concentrations indicate overdose to be the cause of fetal death. Maternal disseminated intravascular coagulation (DIC) may have been related to maternal acetaminophen-induced liver disease alone or to a combination of liver disease and the presence of a dead fetus.