In patients with cystinosis, the concentration of free cystine in leukocytes was 80 times greater than normal, and six times the normal content for their parents. This is the first demonstration of an abnormality in heterozygotes for this rare inherited disease of childhood. Three-quarters of the cystine was recovered in the granular fraction of cystinotic leukocytes.

The large amount of cystine compartmentalized in cystinotic leukocytes cosediments in isopycnic sucrose density gradients with dense lysosomal particles, within which it is presumably contained. Such cystine appears to be primarily noncrystalline in these organelles.

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A B S T R A C T The presence of collagen in lung is fundamental in normal lung structure and function. Methods have been developed to examine human fetal and adult lung collagen with respect to its composition and synthesis. The second trimester fetal lung has a large number of cells per unit lung mass (36.6±2.7 lsg DNA/mg dry wt) and relatively small amounts of collagen (17.0±5.3 Ag collagen/mg dry wt). The number of cells per unit lung mass in the adult lung (11.1±3.4 Ag DNA/mg dry wt) is 30% of the number of cells in the fetal lung, but the adult has 11 times more collagen (196±25 Ag collagen/mg dry wt).The composition of fetal lung collagen can be partially characterized by extraction with salt at neutral pH, acetic acid, or guanidine. The extracted chains, representing 10% of the total lung collagen, chromatograph as al and a2 chains, each with a mol wt of 100,000 and an animo acid composition characteristic for collagen but not specific for lung.Short-term explant cultures of fetal and adult lung synthesize a chains which can be isolated by ion-exchange chromatography. These chains, representing 30-40% of the total collagen synthesized by the explants, coelectrophorese with extracted collagen chains on acrylamide gels; they are destroyed by clostridial collagenase and they have a mol wt of 100,000.Although the composition of the collagen synthesized by these explants can be only partially characterized, the rate of synthesis of both collagen and noncollagen (1, 2).In the adult, the total amount of collagen and the concentration of collagen per unit lung mass remain constant (3). In the developing rabbit lung, there is a rapid accumulation of the amount of collagen per unit lung mass so that the adult rabbit lung has six times more collagen than the early third trimester rabbit fetal lung (4). This rapid accumulation of collagen is preceded by a shift in emphasis in the types of proteins synthesized by lung cells, manifested by an increase in the rate of incorporation of amino acids into collagen compared to noncollagen lung proteins. As the rabbit matures, the relative rate of collagen synthesis returns to a low level which continues throughout life (4). Analysis of the collagen synthesized by neonatal rabbit lung suggests there are probably four types of collagen present (5).