Array-CGH analyses of murine malignant lymphomas: genomic clues to understanding the effects of chronic exposure to low-dose-rate gamma rays on lymphomagenesis.

We previously reported that mice chronically irradiated with low-dose-rate gamma rays had significantly shorter mean life spans than nonirradiated controls. This life shortening appeared to be due primarily to earlier death due to malignant lymphomas in the irradiated groups (Tanaka et al., Radiat. Res. 160, 376-379, 2003). To elucidate the molecular pathogenesis of murine lymphomas after low-dose-rate irradiation, chromosomal aberrations in 82 malignant lymphomas from mice irradiated at a dose rate of 21 mGy/day and from nonirradiated mice were compared precisely by microarray-based comparative genomic hybridization (array-CGH) analysis. The array carried 667 BAC clones densely selected for the genomic regions not only of lymphoma-related loci but also of surface antigen receptors, enabling immunogenotyping. Frequent detection of the apparent loss of the Igh region on chromosome 12 suggested that most lymphomas in both groups were of B-cell origin. Array-CGH profiles showed a frequent gain of whole chromosome 15 in lymphomas predominantly from the irradiated group. The profiles also demonstrated copy-number imbalances of partial chromosomal regions. Partial gains on chromosomes 12, 14 and X were found in tumors from nonirradiated mice, whereas losses on chromosomes 4 and 14 were significantly associated with the irradiated group. These findings suggest that lymphomagenesis under the effects of continuous low-dose-rate irradiation is accelerated by a mechanism different from spontaneous lymphomagenesis that is characterized by the unique spectrum of chromosomal aberrations.

Mathematical analysis of urea rebound in long-term hemodialysis patients.

Quantifying hemodialysis (HD) treatment requires knowledge of the equilibrated concentrations of the post-HD small molecule rebounds. However, measurement of the equilibrated concentrations is only possible after resting in bed after HD for at least 30 min, and this is often impractical. Therefore, we have analyzed mathematically the time course of post-HD urea rebound, and from this, have derived a new formula for predicting its equilibrated concentration. The blood urea nitrogen (BUN) was measured at 10 time points (immediately following HD, and 0.5, 2.5, 5, 7.5, 10, 15, 20, 25, and 30 min post-HD) in 12 anuric HD patients. The absolute change in the urea rebound (DeltaeqBUN) was approximated (DeltaestBUN) using the equation: DeltaestBUN = b -[1-exp x (-c x time (min))] + a x time (min). After the good correlation between DeltaeqBUN and DeltaestBUN, we compared the value of DeltaeqBUN measured at 30 min (DeltaeqBUN(30)) with that calculated (DeltaestBUN(30)) using only four sample points (immediately following HD, and 2.5, 5 and 10 min post-HD). Based on this result, we tried to predict post-HD BUN at 30 min (estBUN(30)). This study was undertaken to determine whether estBUN(30) may be representative of the equilibrated BUN (eqBUN(30)), and to compare with Kt/V using estBUN(30) and eqBUN(30). There was a significant correlation between DeltaeqBUN and DeltaestBUN (0.97 < r < 0.99, P < 0.001). Thus, there was a significant positive linear correlation between eqBUN(30) and estBUN(30) (eqBUN(30): 25.7 +/- 2.25 mg/dL, estBUN(30): 26.3 +/- 2.31 mg/dL; r(2) = 0.99, P < 0.001). A Kt/V measurement was obtained with single pool model using BUN just after HD (Kt/V(sp)), eqBUN(30) (Kt/V(eq)), and estBUN(30) (Kt/V(est)), and with double pool model using Kt/V(sp) (Kt/V(dp)) and was compared with them. Though Kt/V(sp) was significantly higher than Kt/V(eq) (1.26 +/- 0.08 vs. 1.09 +/- 0.07, P < 0.001), there were no differences among Kt/V(eq), Kt/V(est) and Kt/V(dp) (Kt/V(est): 1.06 +/- 0.07, Kt/V(dp): 1.10 +/- 0.07) and all values were clinically acceptable. Furthermore, there was a significant positive linear correlation between Kt/V(eq) and Kt/V(est) (r(2) = 0.98, P < 0.001). In conclusion, we have devised the method to predict equilibrated BUN and calculate double pool Kt/V, which requires samples up to 10 min post-HD.

[Acute encephalopathy due to thiamine deficiency with hyperammonemia in a chronic hemodialysis patient: a case report].

Hemodialysis(HD) patients are at risk for thiamine deficiency because of low intake and accelerated loss of thiamine during HD. We report here an HD patient, an 82-year-old woman, who developed acute encephalopathy due to thiamine deficiency with hyperammonemia. She was admitted to Nishikawa Town Hospital due to pneumonia and was treated with ABPC/SBT for one week. While she was cured of pneumonia, she had a persistently poor appetite. On the twenty-fourth day after admission, HD with intradialytic parenteral nutrition(IDPN), which consisted of 10% glucose 500 ml, in order to correct her malnutrition, was started. She suddenly presented confusion, speech disturbance and ophthalmoplegia. HD with IDPN was stopped after two hours because of her symptoms. Laboratory studies disclosed plasma glucose of 186 mg/dl and serum ammonium of 155 micrograms/dl. Arterial blood gas analysis(inhaling 3 l/min O2) showed severe metabolic acidosis and respiratory acidosis (pH 7.138, pCO2 44.8 mmHg, pO2 108.9 mmHg, HCO3- 15.1 mmol/l). Her malnutrition, unexplained metabolic acidosis and neurological presentation raised the suspicion of acute encephalopathy due to thiamine deficiency. Fursultiamine 100 mg was administered intravenously. After two hours, metabolic acidosis disappeared (pH 7.437, pCO2 33.9 mmHg, pO2 161.0 mmHg, HCO3- 22.9 mmol/l), and she regained her clear consciousness and serum ammonium decreased at 16 micrograms/dl on the next morning. Serum lactate and thiamine level were shown later to be 57.5 mg/dl and 27 nmol/l, respectively. Her clinical course suggests that the glucose load including IDPN may have caused deterioration of the neurological disorder under the condition of thiamine deficiency. Furthermore, it is possible that a relationship exists between thiamine deficiency and hyperammonemia.