Amino acid incorporation into protein by chloroplasts and chloroplast ribosomes is more sensitive to inhibition by chloramphenicol than amino acid incorporation into protein by cytoplasmic ribosomes (3,4). Chloramphenicol also inhibits the formation of some chloroplast enzymes without affecting cell division in Euglena (11) or leaf development in bean (8,9). Chloramphenicol also selectively increases the proportion of 70 S ribosomes present as polysomes (6). Chloramphenicol is bound to chloroplast 70 S ribosomes but not to 80 S cytoplasm ribosomes of Euglena (1). These observations have led to the conclusion that chloramphenicol inhibits protein synthesis by chloroplasts, but not protein synthesis by the cytoplasm, as was suggested by Stutz and Noll (13 lated bean leaves (8). The inhibition by chloramphenicol of lightdependent development of photosynthetic activity varies in approximately the same way as the inhibition by chloramphenicol of amino acid incorporation into protein by chloroplasts (Fig. 1, upper). Likewise, inhibition by chloramphenicol of chlorophyll accumulation during illumination of etiolated leaves varies in the same way as inhibition by chloramphenicol of amino acid incorporation into protein by plastids (Fig. 1, lower). These correlations are meaningful only if the concentration of chloramphenicol in leaves during greening is approximately the same as the concentration of chloramphenicol applied to the leaves. Therefore, the absorption of chloramphenicol by leaves was measured. Leaves were treated with chloramphenicol solutions according to the procedure which was used previously to determine the effect of antibiotic on the formation of photosynthetic activity and chlorophyll (8). The chloramphenicol content of leaves was determined as follows. The leaves were picked, rinsed thoroughly, blotted dry, weighed, and stored frozen. The frozen leaves were ground with water in a Tenbroeck homogenizer. Insoluble material was removed by centrifugation and was washed once. Extract and washing were combined and heated 5 min at 100 C. Coagulated protein was removed by centrifugation and the supernatant liquids were stored frozen. Extracts were assayed for chloramphenicol by measuring inhibition of growth of Escherichia coli ATCC 10536 turbidimetrically (2,14).3 Extracts of leaves had no effect on the growth of E. coli unless the leaves had been treated with antibiotic. Heating standard solutions of chloramphenicol for 5 min at 100 C had no effect on the inhibition of growth of E. coli by chloramphenicol.Five hours after leaves were placed in 100 Ag/ml chloramphenicol, the concentration of antibiotic in the leaves was about 50 Ag/g fresh weight of leaves (Table I). This result shows that the concentration of chloramphenicol in leaves reaches half the concentration applied, early in the greening process. Thus, chlorophyll accumulation and formation of photosynthetic ac3The following modifications were made in the assay procedure.
Observations on the course of 59 children who experienced 109 distinct episodes of CNS involvement by leukemia showed that: 1. This complication may be associated with all types of acute and subacute leukemia. 2. There is no single or combination of diagnostic criteria. Manifestations of increased CSF pressure, such as vomiting, headache, and papilledema are the most frequent clinical findings. However, it should be emphasized that CNS involvement may be associated with normal CSF findings. 3. CNS involvement may be present at the onset of leukemia or can occur at any time during the course. 4. Approximately 26 per cent of children with leukemia develop CNS involvement. 5. CNS involvement may occur when the disease is under apparently good therapeutic control as well as during relapse. 6. There is no relationship between the agents which had been previously used to treat the systemic disease and the later development of CNS involvement. However, the onset of CNS symptoms was less frequent when the systemic disease was under treatment with steroids. 7. The development of CNS involvement does not appear to shorten the survival time of patients with leukemia when treatment for CNS involvement is given.
The results of the first study of the Leukemia Chemotherapy Cooperative Study Group A for the evaluation of two treatment programs in acute leukemia are reported. The cases were accumulated in a period of 15 months. One hundred and twenty-five of the 168 patients started on the study were considered adequately treated and suitable for analysis. The 43 cases excluded from evaluation consisted of patients whose therapy was changed to steroids, those expiring while on treatment, and those lost for follow-up or drug errors. In 125 cases of previously untreated acute leukemia in children, no significant difference was seen in the percentage of complete remissions obtained when 6-mercaptopurine was used alone or when 6-mercaptopurine and azaserine were used in combination. The duration of the remissions obtained with the combined therapy was not significantly longer than when 6-mercaptopurine was used alone.
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