Osborne W R, Hammond W P, Dale D C
J Lab Clin Med. 1985 Apr;105(4):403-9.
It appeared possible that abnormal purine or pyrimidine metabolism could cause cyclic hematopoiesis by analogy with the defective lymphopoiesis associated with inherited deficiencies of adenosine deaminase and purine nucleoside phosphorylase. Therefore, we examined erythrocyte purine and pyrimidine nucleotide levels, as well as plasma purine and pyrimidine nucleosides and bases in three patients and in normal controls. These studies showed that during neutropenia there was a significant elevation in the levels of guanosine triphosphate (P = 0.005) and adenosine triphosphate (P less than 0.001) in the patients' red cells not attributable to reticulocyte variation. Serial analysis of a patient's plasma showed a fivefold elevation of hypoxanthine (10.6 mumol/L) during neutropenia, with a return to normal values (1.4 mumol/L) as neutrophil numbers increased. Plasma inosine was also significantly elevated in comparison with normal control values (2.0 mumol/L vs. 0.8 mumol/L), whereas plasma and urinary uric acid were within the normal range. Serial analysis of red cells and plasma from two patients with chronic neutropenia showed no elevations of purine or pyrimidine metabolites. These results provide evidence of a link between abnormal concentrations of purine metabolites and cyclic hematopoiesis, and permit the speculation that aberrant purine metabolism is primarily related to the defective hematopoietic cell proliferation that is characteristic of this disease.
类似于与腺苷脱氨酶和嘌呤核苷磷酸化酶遗传性缺乏相关的淋巴细胞生成缺陷，异常的嘌呤或嘧啶代谢可能导致周期性造血。因此，我们检测了3例患者及正常对照者红细胞中的嘌呤和嘧啶核苷酸水平，以及血浆中的嘌呤和嘧啶核苷及碱基。这些研究表明，在中性粒细胞减少期间，患者红细胞中的三磷酸鸟苷水平显著升高（P = 0.005），三磷酸腺苷水平显著升高（P < 0.001），这并非由于网织红细胞变化所致。对一名患者血浆的系列分析显示，在中性粒细胞减少期间次黄嘌呤升高了5倍（10.6 μmol/L），随着中性粒细胞数量增加恢复到正常水平（1.4 μmol/L）。与正常对照值相比，血浆肌苷也显著升高（2.0 μmol/L对0.8 μmol/L），而血浆和尿尿酸在正常范围内。对两名慢性中性粒细胞减少患者的红细胞和血浆进行系列分析，未发现嘌呤或嘧啶代谢产物升高。这些结果提供了嘌呤代谢产物浓度异常与周期性造血之间存在联系的证据，并推测异常的嘌呤代谢主要与该疾病特征性的造血细胞增殖缺陷有关。
