The levels of cyclic GMP and glucose 1,6-diphosphate,and the activity of phosphofructokinase,in muscle from normal and dystrophic mice

A striking reduction in the levels of glucose 1,6-diphosphate and an increase in cyclic GMP were found in muscle from dystrophic mice. Concomitant to these changes, the allosteric activity of phosphofructokinase was found to be markedly reduced. These findings could offer an explanation for the observed reduction in glycolysis in the dystrophic muscle.     

Cellular changes in the bone marrow of Plasmodium berghei-infected mice: II. Blast transformation and phagocytosis

The present work is concerned with early cellular changes occurring during a malaria infection. Blast transformation by lymphoid cells and phagocytosis by adherent cells from the bone marrow was performed, using immune and nonimmune Balb/c mice. Nonadherent bone marrow cells from immune mice show an increased specific lymphoblast transformation. This increase was not observed during a lethal infection (PI). Adherent bone marrow cells were assayed for phagocytosis of parasitized (PE) or normal erythrocytes (NE). Cells from immune mice show an increase in phagocytosis of PE and NE. Cells from PI mice showed a decreased phagocytosis throughout the infection, beginning at Day 1 after challenge.     

The Promise of Pharmacogenomics in Reducing Toxicity During Acute Lymphoblastic Leukemia Maintenance Treatment

Pediatric acute lymphoblastic leukemia(ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2–3 years. While the primary drugs used in the maintenance phase, 6-mercaptopurine(6-MP) and methotrexate(MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity. For both drugs, pharmacogenomic factors have been identified that could explain a large amount of the variance in toxicity between patients, and may serve as effective predictors of toxicity during the maintenance phase of ALL treatment.6-MP toxicity is associated with polymorphisms in the genes encoding thiopurine methyltransferase(TPMT), nudix hydrolase 15(NUDT15), and potentially inosine triphosphatase(ITPA), which vary between ethnic groups. Moreover, MTX toxicity is associated with polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1(SLCO1B1) and dihydrofolate reductase(DHFR). Additional polymorphisms potentially associated with toxicities for MTX have also been identified, including those in the genes encoding solute carrier family 19 member 1(SLC19A1)and thymidylate synthetase(TYMS), but their contributions have not yet been well quantified. It is clear that pharmacogenomics should be incorporated as a dosage-calibrating tool in pediatric ALL treatment in order to predict and minimize the occurrence of serious toxicities for these patients.