Retrospective analysis of clonality and detection of residual disease in myeloid leukemia by FISH on long-term stored bone marrow smears

Abstract Background. Fluorescence in situ hybridization (FISH) has allowed the detection of numerical chromosomal aberrations in interphase nuclei on fresh or frozen smears of leukemia.
Methods. To analyze clonality and residual disease in myeloid leukemia retrospectively, we applied FISH to bone marrow smears stored at ambient temperature for up to 9 years.
Results: When hybridization efficiency was investigated on stored control smears from patients without hematological malignancy, more than 96% of nuclei showed the expected number of signals using DNA probes specific for chromosome 7, X or Y. In combination with cell morphology, we observed much higher hybridization efficiency in blasts and granulomonocytic cells compared with lymphoid and erythroid cells. On the basis of good hybridization efficiency for old smear specimens, we applied FISH to stored bone marrow smears of myeloid leukemias, in which either loss of chromosome 7 or loss of sex chromosomes had been verified previously by conventional cytogenetics (one patient with chronic myelomonocytic leukemia (CMML) and four with acute myeloid leukemia (AML; three M2 and one M7)). As a result, the loss of chromosome was detected in blasts from all patients and was observed in mature granulocytes, except in M7. In the CMML patient and one AML (M2) patient with t(8;21), lymphoid and erythroid cells also showed the loss of chromosomes, suggesting that it should occur at stem-cell level. A high amount of residual disease was detected in the morphological remission samples in one AML (M2) patient after induction therapy. The patient eventually succumbed to relapse.
Conclusion Thus, the present FISH technique is useful to analyze the clinical significance of clonality and the residual disease in myeloid leukemia, retrospectively.     

Changes in levels of serum erythropoietin, serum iron and unsaturated iron binding capacity during chemotherapy for lung cancer

BACKGROUND: The serum erythropoietin level increases markedly during chemotherapy for leukemia. A number of hypotheses have been built for the mechanism, none of them satisfactory. Difficulty in evaluating bone marrow activity hampers the elucidation. Therefore, we focused on patients who had non-hematological cancer and no evidence of bone marrow suppression. METHODS: Twelve patients, who had lung cancer (four with small cell cancer and eight with non-small cell cancer) and who had not undergone any chemotherapy, were studied. During chemotherapy, we measured serum erythropoietin, serum iron, unsaturated iron binding capacity and hemoglobin concentration in these patients. RESULTS: The serum erythropoietin level before chemotherapy (10.8 +/- 7.4 mU/ml) was within the normal range but the peak values after the first treatment (73.4 +/- 90.4 mU/ml) increased in all patients. In the patients with small cell cancer, a transient but marked increase in erythropoietin value (204.6 +/- 167.3 mU/ml) was observed after each session of chemotherapy while hemoglobin concentration decreased gradually. Throughout treatments, elevation of the serum iron concentration and concomitant reduction of unsaturated iron binding capacity were observed after each session of chemotherapy. They regained their original values whilst the serum erythropoietin level decreased after each chemotherapy session was completed. CONCLUSIONS: It is suggested that the suppression of erythroid marrow by chemotherapeutic agents causes the changes in serum erythropoietin level during chemotherapy in patients with lung cancer.      

小柴胡汤对鼠实验性肝纤维化的影响

目的:探讨小柴胡汤对鼠肝纤维化的抑制作用及该抑制作用与活性伊东细胞间的相互关系。方法:分别腹腔注射二甲基亚硝基胺和猪血清复制两种肝纤维化动物模型并投予小柴胡汤观察其预防与治疗作用。结果:小柴胡汤可促进肝维生素 A 含量恢复;降低肝胶原含量和明显抑制肝前α-Ⅰ型胶原的基因表达;显著减少Ⅰ、Ⅲ型胶原在肝脏沉积,明显减少。α-平滑肌原纤维阳性的伊东细胞的数目。结论:小柴胡汤可防治鼠肝纤维化的发生与发展。     

D1 dopamine receptor activation reduces extracellular glutamate and GABA concentrations in the medial prefrontal cortex

The present study examined effect of administration of a selective D1 dopamine receptor agonist, SKF38393 on extracellular concentrations of glutamate (Glu) and gamma-aminobutyric acid (GABA) in mPFC, by using in vivo microdialysis. Perfusion with SKF38393 via a dialysis probe reduced concentrations of both Glu and GABA dose-relatedly, and these effects were prevented by co-perfusion with a D1 dopamine receptor antagonist, SCH23390 (40 microM). These results suggested that the dopaminergic hyperactivity may lead to the hypofunction of glutamatergic and GABAergic systems in mPFC via D1 dopamine receptor stimulation.     

Assessment of intestinal viability using a non-contact laser tissue blood flowmeter

BACKGROUND: Intraoperative assessment of small intestinal viability following ischemic insult from arterial occlusion has remained difficult. The purpose of the present study was to assess the applicability of non-contact tissue blood flowmeter (NCLBF) with regard to intraoperative assessment of intestinal viability. METHODS: Using the ischemia-reperfusion model of rabbits, the relationship between the records of NCLBF, pulse oximetry (PO), and histological grade and the comparison of accuracy of intestinal viability among NCLBF, PO, and fluorescein (FL) were examined. RESULTS: There was a significant relationship between NCLBF and the histological grade (coefficient-0.80, P <0.0001); however, PO was not related. The accuracy and sensitivity of bowel viability of NCLBF (76%, 88%) were better than those of PO (58%, 23%) and FL (48%, 4%), respectively (P <0.001). CONCLUSIONS: NCLBF is useful to assess intestinal viability, suggesting the possibility of clinical use.