FREE AMINO ACIDS IN BLOOD. II 385 
very frequent intervals would be necessary to determine the exact nature and signif- 
icance of these changes. 
DISCUSSION 
The findings in patients with chronic granulocytic leukemia and the patient with 
polycythemia make it apparent that there are certain deviations from the normal 
free amino acid patterns in plasma and cells. These deviations are variable and the 
free amino acid levels may be well within the normal range on many occasions. As 
has been noted above, there is a definite tendency for patients with chronic granulo- 
cytic leukemia and polycythemia to show elevations of all free amino acids on some 
occasions and on other occasions the plasma glutamic acid level may be elevated with- 
out any appreciable change in the other free amino acids. Many of the plasma 
samples had a glutamine level that was at the lower limit seen in any normal indi- 
vidual on a number of occasions, and the impression is thus gained that, except 
when there is an elevation of total free amino acids, glutamine tends to be somewhat 
reduced in the plasma of patients with granulocytic leukemia. Quantitative values 
are also in agreement with this concept (see Figs. 377 and 378 of part VI). 
The most marked and consistent deviations from normal were observed in three 
humans and a dog that had in common the somewhat unusual finding of go°%, or 
more neutrophilic polymorphonuclear leukocytes in the peripheral blood. In these 
cases the plasma glutamic acid level was distinctly elevated; leukocytes and platelets 
showed the elevation of glutamic acid and a very low glutamine level. The erythro- 
cytes from the three patients did not show the glutamine and glutamic acid changes 
seen in the plasma, leukocytes, and platelets, but the dog erythrocytes showed the 
changes clearly. The urine did not appear to reflect the changes seen in the blood. 
It is to be noted that, although rare, granulocytic leukemia has been encountered in 
dogs by other investigators?%> 24, 
It is of particular interest that where morphologically similar (and almost identical) 
leukocytes could be compared from normal individuals and patients with granulocytic 
leukemia and polycythemia, the leukemic cells proved to be distinctly different from 
normal. Leukocytes from other types of leukemia may be abnormal, but it is not 
possible to obtain morphologically similar cells from normal individuals for direct 
comparison. That the changes seen in the polymorphonuclear leukocytes are not 
specific for leukemia is indicated by the fact that similar findings were obtained in 
the plasma, leukocytes, and erythrocytes of a patient with reticulum cell sarcoma?. The 
finding of an elevated plasma glutamic acid level is in keeping with previous reports 
of WHITE ef al.2-", and the low glutamine level in some of the white cells is in keep- 
ing with the findings of RoBERTS AND FRANKEL! with transplantable tumor cells. 
It is perhaps surprising that patients with such large increases in the myeloid 
series of cells do not always show distinctly abnormal plasma free amino acid levels. 
The myeloid system is one of the major organs of the body in these patients. The 
absence of such changes can be explained in part by 7m vitro studies (reported in 
part I). Very little change in the free amino acid pool of myeloid cells is noted when 
blood is allowed to stand for as long as 4 h at room temperature. This indicates that 
the cells do not degrade free amino acids rapidly. The major tendency to produce a 
deviation from the normal amino acid levels of plasma would be by the uptake of 
amino acids by the cells or the metabolism of other substances. This uptake is limited 
References p. 447/448 
