Relationship of deoxycytidine kinase and cytoplasmic 5'-nucleotidase to the chemotherapeutic efficacy of 2-chlorodeoxyadenosine

The agent 2-chlorodeoxyadenosine (2-CdA) has chemotherapeutic activity in hairy cell leukemia (HCL) and in refractory chronic lymphocytic leukemia (CLL). The cytotoxic activity of 2-CdA requires the intracellular accumulation of 2-CdA nucleotides. Deoxycytidine kinase (dCK) and cytoplasmic 5'-nucleotidase (5'-NT) are the principal enzymes that phosphorylate 2-CdA and dephosphorylate 2-CdA 5'-monophosphate, respectively. The net accumulation of 2-CdA nucleotides may therefore depend on both dCK and 5'-NT. The purpose of the present experiments was to determine if there is a relationship between pretreatment levels of dCK and 5'-NT in HCL and in CLL cells, and the clinical outcome of 2- CdA treatment. As measured by a direct immunoassay for dCK in 25 CLL patients, and by a 5'-NT activity assay in 23 patients, mean dCK levels were significantly higher in 2-CdA responders than in nonresponders (P < .01), whereas mean 5'-NT levels were significantly lower in 2-CdA responders than in nonresponders (P < .05). Mean dCK levels were higher in six HCL 2-CdA responders than in one nonresponder, whereas mean 5'- NT levels were lower in the 2-CdA responders than in the nonresponder. These results suggest that both dCK and 5'-NT are determinants of 2-CdA responsiveness.     

Partial flip angle MR imaging

Theoretical analysis predicts that performing magnetic resonance (MR) imaging with partial (less than 90 degrees) flip angles can reduce imaging times two- to fourfold when lesions with elevated T1 values are being examined. This time savings occurs because repetition time (TR) is reduced when imaging is performed with partial flips. Partial flip MR imaging can also improve signal-to-noise ratio (S/N) in fast body imaging. For this study, analytical tools were used to predict image contrast and S/N for short TR, partial flip sequences. Experimental implementation of the short TR, partial flip sequences that analytical work had predicted would be optimal supported the analytical predictions and demonstrated their validity. Partial flip MR imaging is applicable to reducing imaging time only when the ratio of signal differences to noise exceeds threshold values in conventional MR images. Partial flip sequences can be used to advantage in MR imaging of both the head and the body, and the observed effects are predictable through theoretical analysis.     

Deficiency of methylthioadenosine phosphorylase in human leukemic cells in vivo

Cells from 20 patients with leukemia and 9 with solid tumors were assayed for the enzyme methylthioadenosine phosphorylase, which function in both purine and polyamine metabolism in rapidly dividing cells. As determined by autoradiography of viable cells, and by direct enzymatic analysis, samples from one individual with pre-T-cell acute lymphoblastic leukemia and one with common acute lymphoblastic leukemia were methylthioadenosine phosphorylase deficient. In contrast, other leukemias of similar antigenic phenotype, as well as normal peripheral blood lymphocytes, thymic lymphocytes, and normal bone marrow cells, had substantial methylthioadenosine phosphorylase activity. This evidence suggests that the complete absence of methylthioadenosine phosphorylase distinguishes some leukemic cells in vivo from their nonmalignant counterparts.     

Evaluation of three oral rehydration solutions designed for use in developed communities

One hundred and sixteen children (less than 2 years old) admitted to a London hospital with acute gastroenteritis were randomized to receive either an oral rehydration solution (ORS) with low sodium and high glucose concentration (Na+ 35, glucose 200 mmol/L), an ORS with a high sodium but low glucose concentration (Na+ 60, glucose 111 mmol/L), or an ORS containing glycine and a glucose polymer (Na+ 50, glucose 50, glycine 50 mmol/L). Clinical, biochemical and haematological features of the three groups were similar on admission. Rotavirus was common (31%); the majority of children had minimal dehydration or acid-base disturbance. The clinical outcome, including ORS intake, prevention of dehydration, rehydration, and duration of hospital stay was similar in the three treatment groups. All initial electrolyte abnormalities were corrected; no child developed hypernatraemia or hyponatraemia. At 24 h, the mean serum urea was higher in those who received the ORS containing glycine than in other groups, and it had not fallen significantly since admission. Eighteen per cent of children had carbohydrate intolerance: four children with greater than or equal to 2% reducing substances in their stool had all received ORS with a high glucose content and had numerous watery green stools containing rotavirus. All ORS solutions were safe and effective for rehydration and correction of biochemical abnormalities, however carbohydrate intolerance was more prevalent in children who received the ORS with a high glucose content.