Immunoelectron microscopic studies on centromere-kinetochore complexes detached from chromosomes

The centromere-kinetochore complexes of Chinese hamster ovary (CHO) cells were detached and separated from the condensed chromatin by treatment with hydroxyurea and caffeine. By labelling the complex for immunoelectron microscopy (immuno-EM) with a mixture of antibodies against centromere proteins (anti-CENP-A,-B, -C) in some cells, we could demonstrate complete detachment of the complexes. No remnants were left at the bulk of condensed chromatin in these cells. In some mitotic cells complex and chromatin were found side by side. It could be shown that the fine structure of the separated material of the complex differs significantly from that of the rest of chromatin. The complex consists of proteins and DNA. This leads us to suppose that the organization of chromatin in the centromere-kinetochore complex is different.     

Contrasting effects of hydroxyurea on cell growth and reduction in Epstein-Barr virus genomes in EBV-infected epithelioid cell lines vs Burkitt's lymphoma cell lines

Eliminating Epstein-Barr virus (EBV) genomes from infected cells is an intriguing theoretical strategy in therapy for EBV-associated malignant diseases. Respective patterns were characterized for hydroxyurea (HU)-promoted loss of EBV genomes from EBV-infected epithelioid cell lines derived from the noncancerous portion of gastric carcinoma tissues and Burkitt's lymphoma (BL) cell lines. Epithelioid cell lines GT38 and PN were less sensitivity to HU than BL cell lines Akata, Raji, and Daudi in terms of cell growth inhibition and cell cycle arrest. On passage in medium with 50 microM HU, the fraction of EBV nuclear antigen (EBNA)-positive cells was reduced substantially in the BL cell lines, but only slightly in the epithelioid cell lines. EBV DNA was reduced in Akata, Raji, and Daudi cells upon passage in 50 microM HU by 95%, 70%, and 50%, respectively, but by only 10% in GT38 cells, in which EBV DNA reduction was enhanced at increased concentrations of HU. This indicates that EBV genome is more easily lost from BL cell lines than from epithelioid cell lines upon culturing in HU. These findings support the view that the elimination of EBV could be therapeutically effective in EBV-associated BL by HU.     

姜黄素与羟基脲对K562细胞的体外联合作用

目的 了解姜黄素与羟基脲合用对人白血病Ｋ５６２细胞的体外作用。方法 采用ＭＴＴ法测定药物的体外杀伤作用,应用ＡＯ／ＥＢ荧光染料染色观察药物诱导细胞凋亡,金氏公式进行联合用药分析。结果 姜黄素５,１０ｕｇ／ｍｌ,羟基脲２５,５０ｕｇ／ｍｌ同时给药,对Ｋ５６２细胞可产生单纯相加的协同杀伤效果。姜黄素与羟基脲同时给药诱导Ｋ５６２细胞凋亡率高于羟基脲单独用药,低于姜黄素单独用药。结论 姜黄素与羟基脲同时联     

Early splenectomy and polychemotherapy versus polychemotherapy alone in chronic myeloid leukemia

The effect of early splenectomy and of polychemotherapy with hydroxyurea, busulfan, and alternate bimonthly courses of arabinosyl cytosine and vincristine plus prednisone, was evaluated in 139 previously untreated patients with chronic myeloid leukemia (CML), consecutively admitted to 18 hospitals from March 1973 to October 1974. Fifty-six patients were splenectomized and 83 patients were not splenectomized. Splenectomy did not influence the duration of chronic and blastic phase, and did not prolong survival. The prognosis of high risk patients was not improved. During the chronic phase, high platelet counts were more frequent in splenectomy group, and five patients developed thrombotic or thromboembolic complications, 5 to 19 months after the operation. The median survival of the whole group was 50 months, with 32 of 139 patients (actuarial proportion 30%) remaining alive 72 months after diagnosis, but the slope of the survival curve was similar to that of historical controls. The results of this trial suggests that new strategies should be developed for the therapy of CML.     

Higher executive abilities following a blood transfusion in children and young adults with sickle cell disease

Individuals with sickle cell disease (SCD) experience cognitive deficits; however, it remains unclear whether medical treatments for SCD improve cognition. Given that executive abilities are typically impaired in individuals with SCD, they were the focus of the current study. Our primary hypothesis was that executive abilities would be higher acutely soon after a blood transfusion in children and young adults with SCD. We used tests from the NIH Toolbox to assess executive abilities in 27 participants with SCD receiving chronic transfusion in comparison to 34 participants with SCD receiving hydroxyurea (HU) and 41 non‐SCD demographically matched controls, all of whom were tested at two time points. Participants in the transfusion group completed cognitive testing within 3 days after a transfusion (soon after transfusion) and then within 3 days before their next transfusion (long after transfusion) over an interval of 3‐7 weeks. We found that executive abilities were significantly poorer for the transfusion and HU groups than for the control group. In support of our primary hypothesis, executive abilities for the transfusion group were significantly better soon after a transfusion compared to long after a transfusion, χ²(1) = 17.8, P < .0001. Our results demonstrate that executive abilities were higher acutely following a blood transfusion. These findings have implications for daily functioning, medical decision making, and academic achievement in children and young adults with SCD.