高+Gx对猴肝细胞c-fos表达的影响

目的:观察航天应急返回过程中高正加速度( Gx)对肝脏细胞c-fos基因表达的影响．方法:选用♂猕猴(共9只)为对象,随机分为4组,对照组承受 1Gx,300 s的超重作用;实验组根据承受过载峰值的大小分为3个亚组,其承受过载峰值分别为 15Gx,200 s; 18Gx, 165 s; 21Gx,140 s．观察高 Gx对猴肝脏细胞c-fos基因表达的影响．结果:实验组肝脏细胞胞质呈现不同程度的水肿及泡状变性,c-fos基因表达明显增强,呈弥漫性细胞质内棕黄色着色;肝细胞c-fos基因表达程度随超重剂量的增加有增强趋势．对照组肝脏组织病理学改变程度明显较实验组轻微,c-fos基因表达亦明显减弱．结论: Gx可引起猴肝脏组织细胞c-fos基因表达增强,提示有早期肝脏组织损伤．     

Chromosomal abnormalities identify high-risk and low-risk patients with acute lymphoblastic leukemia

The importance of banded chromosome analyses in predicting long-term outcome in acute lymphoblastic leukemia (ALL) was evaluated in this follow-up study of 329 patients from the Third International Workshop on Chromosomes in Leukemia. Patients were divided into ten groups according to pretreatment karyotype: no abnormalities, one of the following structural abnormalities [the Philadelphia chromosome, translocations involving 8q24,t(4;11), 14q+, 6q-] or, in the remaining cases, modal number [less than 46, 46, 47 to 50, greater than 50]. Achievement and duration of complete remission (CR) and survival differed among chromosome groups (P less than .0001). Karyotype was an independent prognostic factor for duration of first CR and survival, even when age, initial leukocyte count (WBC), French-American-British (FAB) type, and immunologic phenotype were considered. Among adults, prolonged remission and survival were uncommon in all chromosome groups. Only in the normal karyotype group was median survival even two years. Among children, striking differences in long-term remission and survival were seen depending upon karyotype. Children in the greater than 50 group did best, with 70% remaining in first CR for a median duration in excess of five years. Children in the 47-50, 6q-, and normal karyotype groups also had prolonged survivals. In contrast, certain translocations [t(9;22)(q34;q11), t(4;11)(q21;q14-23), t(8;14)(q24;q32)] identified children who had short survivals, even in the presence of favorable prognostic factors including a low WBC, L1 morphology, and non-T, non-B immunologic phenotype. We conclude that chromosome analysis is required at diagnosis in patients with ALL, and that children with these specific translocations should be managed as having high-risk ALL.     

Rapid engraftment by peripheral blood progenitor cells mobilized by recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in nonhuman primates

We have previously shown that administration of low-dose recombinant human stem cell factor (rhSCF) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) to baboons mobilizes greater numbers of progenitor cells in the blood than does administration of rhG-CSF alone. The purpose of the present study was to determine whether marrow repopulating cells are present in the blood of nonhuman primates administered low-dose rhSCF plus rhG-CSF, and if present, whether these cells engraft lethally irradiated recipients as rapidly as blood cells mobilized by treatment with rhG-CSF alone. One group of baboons was administered low-dose rhSCF (25 micrograms/kg/d) plus rhG- CSF (100 micrograms/kg/d) while a second group received rhG-CSF alone (100 micrograms/kg/d). Each animal underwent a single 2-hour leukapheresis occurring the day when the number of progenitor cells per volume of blood was maximal. For baboons administered low-dose rhSCF plus rhG-CSF, the leukapheresis products contained 1.8-fold more mononuclear cells and 14.0-fold more progenitor cells compared to the leukapheresis products from animals treated with rhG-CSF alone. All animals successfully engrafted after transplantation of cryopreserved autologous blood cells. In animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells, we observed a time to a platelet count of > 20,000 was 8 days +/- 0, to a white blood cell count (WBC) of > 1,000 was 11 +/- 1 days, and to an absolute neutrophil count (ANC) of > 500 was 12 +/- 1 days. These results compared with 42 +/- 12, 16 +/- 1, and 24 +/- 4 days to achieve platelets > 20,000, WBC > 1,000, and ANC > 500, respectively, for baboons transplanted with rhG-CSF mobilized blood cells. Animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells had blood counts equivalent to pretransplant values within 3 weeks after transplant. The results suggest that the combination of low-dose rhSCF plus rhG-CSF mobilizes greater numbers of progenitor cells that can be collected by leukapheresis than does rhG-CSF alone, that blood cells mobilized by low-dose rhSCF plus rhG-CSF contain marrow repopulating cells, and finally that using a single 2-hour leukapheresis to collect cells, the blood cells mobilized by low-dose rhSCF plus rhG-CSF engraft lethally irradiated recipients more rapidly than do blood cells mobilized by rhG- CSF alone.     

Moderate Dose Escalation for Advanced Stage Hodgkin's Disease Using the Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone Scheme and Adjuvant Radiotherapy: A Study of the German Hodgkin's Lymphoma Study Group

The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide,vincristine, procarbazine, and prednisone) regimen, a rearranged andaccelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has beenshown to be effective and safe in a previous pilot study for advanced stage Hodgkin's disease (HD). The present study aimed to determine amaximum practicable dose of three drugs, ie, etoposide, adriamycin, andcyclophosphamide, for which acute toxicities were acceptable and toassess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study.Radiotherapy was given in 44 patients (73%) after chemotherapy toinitial bulk lesions and residual disease. Granulocyte-colonystimulating factor (G-CSF) was given from day 8 to prevent prolongedneutrocytopenia and severe infections. The intended doses ofadriamycin, etoposide, and cyclophosphamide in the BEACOPP schedulecould be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m². The major toxicities were leukocytopenia andthrombocytopenia with considerable heterogeneity between individualpatients. Of 60 patients, 56 (93%) achieved a complete remission (CR).At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95%confidence interval 83% to 99%) and 90% (82% to 98%). Theseresults show that a moderate dose escalation of adriamycin,cyclophosphamide, and etoposide of the baseline BEACOPP regimen isfeasible. The escalated BEACOPP regimen shows very encouraging resultsin advanced stage HD and is now being compared in a randomized phaseIII study with BEACOPP at baseline dose level.     

DNA methylation profiles in the human genes for tumor necrosis factors alpha and beta in subpopulations of leukocytes and in leukemias.

The genomic sequencing technique has been applied to assess the state of methylation in the DNA from human leukocyte subpopulations from healthy individuals and in the DNA from several individuals with myeloid or lymphatic leukemias or non-Hodgkin lymphomas. Leukocyte populations were purified by the high-gradient magnetic cell sorting technique. In the human tumor necrosis factor alpha (TNF-alpha) gene segment between nucleotides 300 and 1150, the specific methylation profile in the DNA from human granulocytes and monocytes is maintained in three cases of myeloid leukemia. In one such case, all 5-methyl-2'-deoxycytidine residues have been replaced by cytidine. In a chronic lymphatic T-cell leukemia, all 5-methyl-2'-deoxycytidine residues have been substituted by cytidine. In normal B lymphocytes, in two cases of chronic lymphatic B-cell leukemias and two cases of non-Hodgkin lymphomas, all 5'-CG-3' sequences in this gene segment are devoid of methylation. In the TNF-beta gene, DNA methylation is decreased in several examples of acute or chronic myeloid leukemias in comparison to normal human granulocytes or monocytes, whose DNA is almost completely methylated between nucleotides 700 and 900. In human T and B lymphocytes, the main producers of TNF-beta, in three instances of chronic lymphatic leukemias and two cases of non-Hodgkin lymphomas, all 5'-CG-3' sequences are unmethylated in this region. The DNA from the human HeLa cell line is highly methylated at all 5'-CG-3' sequences in the TNF-alpha and -beta genes. The TNF-alpha gene is transcribed in the cells of one case of acute myeloid leukemia in which the analyzed region of the TNF-alpha gene is completely unmethylated. The TNF-beta gene is not transcribed in any of the malignant cells tested.     

Cloning and expression of methicillin resistance from Staphylococcus epidermidis in Staphylococcus carnosus.

A 6.2-kilobase chromosomal DNA fragment from a methicillin-resistant Staphylococcus epidermidis strain was cloned into Staphylococcus carnosus by using staphylococcal plasmid pCA44 as the vector. The recombinant plasmid obtained, pBBB21, conferred methicillin resistance on its host and was responsible for the synthesis of a low-affinity penicillin-binding protein (PBP), PBP 2'. PBP 2' determined by the S. epidermidis DNA and expressed as a membrane-bound PBP in S. carnosus reacted with monoclonal antibodies directed against PBP 2' of Staphylococcus aureus origin, and the cloned S. epidermidis DNA hybridized to the methicillin (mec)-specific DNA from S. aureus. These findings point to a common origin of the methicillin resistance determinant in staphylococci.     

不同胰岛素促泌剂单药治疗对2型糖尿病患者死亡率和心血管风险的影响

研究纳入丹麦1997～2006年间107806例起始胰岛素促泌剂或二甲双胍单药治疗的2型糖尿病患者(年龄>20岁,没有使用过胰岛素单药和联合治疗)其中9607例患者既往存在心肌梗死史.随访时间3.3年,每3个月为一个区间,收集不同胰岛素促泌剂或二甲双胍的处方,如果某区间无处方量则以之前最多3个处方量的区间 作为参考.