No abstract

Recent findings in different mammalian species have demonstrated that XY embryos grow faster than XX embryos before the gonads are differentiated. In mice and cattle, accelerated development is already evident in XY blastocysts, while in the rat and in human fetuses a quantitative sex difference has been shown to be present before testicular differentiation has occurred. These data demonstrate that in these species the histological differentiation of the testis, which occurs early and rapidly, is preceded by an increased growth rate of the embryo. This may be expected to increase the probability of the gonad reaching the threshold for testis development, since it is known that developmental delay can result in ovarian differentiation. It is postulated that the fast development of the male may be an adaptation to the reproductive biology of eutherian mammals, in which development of both sexes occurs in the hormonal environment of the uterus. The question is raised as to a possible connection between sex-related growth and other sex differences, such as longevity.

A premature baby of 32 weeks gestation and weighing 1.7 kg (3 lb 12 oz), with a defect in each iris and anomalous genitalia, showed XXY triploidy on chromosome analysis. Extensive blood grouping was consistent with both digyny and diandry, but the former was more likely. Two abortuses, received as part of a survey of spontaneous abortions, revealed XXX triploidy on tissue culture. One showed a fusion defect of the neural tube; both showed late or defective fusion of the embryonic cleft of the iris. In both a small proportion of nuclei in the amnion showed two Barr bodies. In two cases in which measurements of nuclear volume were made this was about 50% greater than in diploid controls.

Dent & Rose (1951) using the technique of paper chromatography demonstrated that in the urine of patients with cystine stone formation, not only cystine, but also lysine and arginine were consistently present in abnormally large concentrations. By the methods used it was not possible to be certain whether or not ornithine was present in appreciable amounts, nor could satisfactory quantitative data for any amino-acid be obtained. Stein (1951), using the procedure of elution chromatography with an ion-exchange resin, studied quantitatively the amino-acid content of urine samples from five patients with cystine stone formation and was able to demonstrate in all of them abnormal amounts of cystine, lysine, arginine and ornithine. The average values for the 24 hr. excretion in these five patients were: cystine 0.73 g., lysine 1.8 g., arginine 0.83 g. and ornithine 0.37 g. Other amino-acids were not present in greater concentrations than occur in normal urine.Harris & Warren ( I Y53), estimating cystine polarographically, showed that among the relatives of patients with cystine stone formation many individuals occurred who, while being quite healthy, nevertheless excreted abnormal amounts of cystine. I n fact, among such relatives every degree of cystine excretion could be found between normal values and the very high value encountered in patients with cystine stone formation. Genetical analysis suggested that the people with moderately increased cystine output were only encountered in certain families. It was thought that these people were heterozygous for a gene which in homozygous form led to the very high cystine excretion found in patients with cystine stone formation.The present paper is concerned with the pattern of excretion of lysine and arginine among cystinuric patients and their relatives over the whole range of cystine excretion, from normal values to the values found in patients with stone formation. This investigation is a necessary preliminary to further studies on the underlying disturbances in physiological function in these individuals and to the progressive differentiation of the various genotypes involved. MATERIAL AND METHODSUrine samples from twenty-eight cystinuric patients and 121 of their relatives were st'udied. In many of these cases rnore than one specimen from the same individual has been examined. Urines from 250 unselected individuals were also examined. The urine samples were early morning specimens, preserved with thymol, and usually sent to the laboratory by post. They were kept frozen until the initial determinations were performed, and subsequently kept at 2°C.Cystine and creatinine were determined as in our previous work (Harris & Warren, 1953); lysine and arginine were determined microbiologically ; qualitative examination of the urines for amino-acids were carried out by two-dimensional paper chromatography (phenol-ammonia/ STEIN, W. H. (1953). A chromatographic investigation of the amino acid constituents of normal urine. STEIN, \V. H. & MOORE, S. (1951). Electrolytic desalting ...