In vivo dynamics of stable chronic lymphocytic leukemia inversely correlate with somatic hypermutation levels and suggest no major leukemic turnover in bone marrow.

Although accumulating evidence indicates that chronic lymphocytic leukemia (CLL) is a disease with appreciable cell dynamics, it remains uncertain whether this also applies to patients with stable disease. In this study, (2)H(2)O was administered to a clinically homogeneous cohort of nine stable, untreated CLL patients. CLL dynamics in blood and bone marrow were determined and compared with normal B-cell dynamics in blood from five healthy individuals who underwent a similar (2)H(2)O labeling protocol. Average CLL turnover rates (0.08-0.35% of the clone per day) were approximately 2-fold lower than average B-cell turnover rates from healthy individuals (0.34-0.89%), whereas the rate at which labeled CLL cells in blood disappeared (0.00-0.39% of B cells per day) was approximately 10-fold lower compared with labeled B cells from healthy individuals (1.57-4.24% per day). Leukemic cell turnover variables inversely correlated with the level of somatic hypermutation of the CLL clone (IgVH mutations). Although CLL cells in bone marrow had a higher level of label enrichment than CLL cells in blood, no difference between proliferation rates and proapoptotic and antiapoptotic profiles of CLL cells from these compartments was observed. These data suggest that, in stable disease, there is a biological relationship between the degree of somatic hypermutation of the CLL clone and its dynamics in vivo. Furthermore, in contrast to lymph nodes, the bone marrow does not seem to be a major CLL proliferation site.

Short-term protein intake and stimulation of protein synthesis in stunted children with cystic fibrosis.

BACKGROUND: Stunted children with cystic fibrosis (CF) have less net protein anabolism than do children without CF, and the result is retarded growth in the CF patients. It is not known whether protein intake above that recommended by the Cystic Fibrosis Foundation would further stimulate whole-body protein synthesis. OBJECTIVE: We studied the effects of 3 amounts of protein intake on whole-body protein synthesis and breakdown by using isotopic infusion of [1-(13)C]valine and [(15)N(2)]urea in children with stable CF who required tube feeding. DESIGN: In 8 pediatric CF patients, we administered 3 randomly allocated isocaloric diets with normal (NP), intermediate (IP), and high (HP) amounts of protein (1.5, 3, and 5 g . kg(-1) . d(-1), respectively) by continuous drip feeding during a 4-d period at 6-wk intervals. Each patient acted as his or her own control. On the fourth day of feeding, whole-body protein synthesis and breakdown were measured. RESULTS: Protein synthesis was significantly higher in the HP group (x +/- SEM: 1.78 +/- 0.07 micromol . kg(-1) . min(-1)) than in the IP (1.57 +/- 0.08 micromol . kg(-1) . min(-1); P=0.001) and NP (1.37 +/- 0.07 micromol . kg(-1) . min(-1); P < 0.001) groups. There were no significant differences in protein breakdown. Net retention of nitrogen was significantly higher in the HP group (12.93 +/- 1.42 micromol . kg(-1) . min(-1)) than in the IP (7.61 +/- 1.40 micromol . kg(-1) . min(-1); P=0.01) and HP (2.48 +/- 0.20 micromol . kg(-1) . min(-1); P < 0.001) groups. CONCLUSION: In stunted children with CF requiring tube feeding, the highest stimulation of whole-body protein synthesis was achieved with a short-term dietary protein intake of 5 g . kg(-1) . d(-1).

Adiponectin and glucose production in patients infected with Plasmodium falciparum.

Infections are often complicated by an increase in glucose production due to stimulation of the secretion of glucose counter-regulatory hormones and cytokines. Adiponectin, a fat-derived hormone with insulin-sensitizing properties, could play a regulatory role in the degree of stimulation of glucose production by the infectious agent. Therefore, we investigated the possible correlation between glucose production and plasma adiponectin levels in 25 subjects: 7 patients with cerebral malaria, 6 with uncomplicated malaria, and 12 matched controls. Glucose production was significantly higher in patients with malaria compared to healthy controls (P < .001). Adiponectin levels were not different between the patients with malaria and the control group. However, patients with cerebral malaria had significantly higher values for adiponectin than the patients with uncomplicated malaria (P < .005). Glucose production and gluconeogenesis were positively correlated to plasma adiponectin in the patients (r = 0.835, P < .001 and r = 0.846, P < .001, respectively), whereas these correlations were absent in the controls (r = -0.329, NS and r = -0.028, NS, respectively). In conclusion, adiponectin levels were not different between patients with malaria and their matched controls. However, patients infected with Plasmodium falciparum who have higher glucose production also have higher adiponectin levels. In healthy subjects such a correlation was not found. As adiponectin is known to inhibit glucose production, stimulation of adiponectin secretion during infection could be intended to restrain the glucose production stimulating properties of hormones and cytokines secreted during infection.