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31.
The feasibility of in vitro interleukin 2 (IL-2) activation and expansion of mononuclear cells (MNCs) derived from adult patients with acute myelogenous leukemia (ANLL) was studied. Patients' natural killer (NK) and lymphokine-activated killer (LAK) cell activity was compared with that of normal donors in terms of: (a) cytolytic activity (four- hour 51Cr release assay) against an NK-sensitive target (K562), NK- resistant targets (Raji/Daudi), and fresh/cryopreserved autologous and allogeneic leukemic blasts; (b) proliferation and expansion in culture with 1,000 U/mL recombinant IL 2 (rIL 2); and (c) the cell surface phenotype of the cultured cells. In 21 of 24 patients with active disease (AP) MNCs derived from the peripheral blood (PBL) or bone marrow (BM) could be cultured and expanded in the presence of rIL 2. These cultures initially contained between 30% and 50% blasts, and during 2 to 4 weeks of culture destruction of blasts and enrichment of up to 60% in cells with the morphology of large granular lymphocytes (LGLs) was observed. Expansion in culture varied between two- and 100- fold. MNCs from all patients in remission (RP) could be activated by rIL 2 and expanded up to 30-fold after 1 to 3 weeks in culture. NK activity of fresh PBLs from AP was significantly lower than in normal controls, whereas NK activity of RP was within the normal range. High levels of postactivation NK and LAK activity on K562/Raji/Daudi and on fresh/cryopreserved leukemic blasts was generated in approximately 50% of cases of AP and in most RP. Cell surface phenotype studies showed that cultured cells derived from ANLL patients were significantly enriched (up to 40%) in NKH-1 (Leu 19) positive cells, with RP LAK cells also expressing a high proportion of CD16 positive cells (up to 40%). This study has shown that it is feasible to activate and significantly expand killer cells derived from active disease and remission ANLL patients during 1 to 3 weeks culture with IL 2 with good maintenance of cytolytic activity. Both initial NK activity and LAK generation was optimal in remission patients. Based on data from this study, a clinical protocol has been developed for treatment of early relapse ANLL patients with LAK cells cultured for 1 to 3 weeks and systemic IL 2. 相似文献
32.
We report the successful long-term engraftment of normal male donor bone marrow (BM) transfused into noncytoablated female mice, challenging the assumption that "niches" need to be created for marrow to engraft. We have used chromosomal banding and Southern blot analysis to identify transplanted male marrow cells, and shown the long-term stability of the chimeric marrows. Balb/C, BDF1, or CBA-J female hosts (no irradiation) received for 5 consecutive days 40 x 10(6) male cells (per day) of the same strain, and repopulation patterns were observed. Parallel studies were performed using tibia/femur equivalents of normal marrow or marrow from Balb/C mice pretreated 6 days previously with 150 mg/kg 5-fluorouracil (5-FU). Chromosome banding techniques showed that 5% to 46% of marrow cells were male 3 to 9 months posttransplant with normal donor marrow. Southern blot analysis, using the pY2 probe, showed continued engraftment at 21 to 25 months posttransplant, ranging from 15% to 42% male engrafted cells in marrow. Normal donor male marrow engrafted significantly better than 5-FU-pretreated male marrow as shown 1 to 12 months posttransplant in non-cytoablated female recipients. Percentages of male engrafted cells in BM ranged from 23% to 78% for recipients of normal donor marrow and from 0.1% to 39% for recipients of 5-FU marrow. Mean engraftment for 6 mice receiving normal marrow was 38%, whereas that for 6 mice receiving post-5-FU marrow was 8%, as assayed 1 to 3 months posttransplant. At 10 to 12 months, mean engraftment for the normal donor group was 46%, compared with 16% for the 5-FU group. The patterns of engraftment with normal and 5-FU marrow were similar for spleen and thymus. These results show that long-term chimerism can be established after transplantation of normal donor marrow to normal nonirradiated host mice and indicate that marrow spaces do not have to be created for successful engraftment. They suggest that transplanted marrow competes equally with host marrow for marrow space. Finally, these data show that post-5-FU Balb/C male marrow is markedly inferior in the repopulation of Balb/C female host marrow, spleen, and thymus, and suggest that this population of cells may not be the ideal population for gene transfer studies. 相似文献
33.
34.
P Laws A Barton RB Warren 《Journal of the European Academy of Dermatology and Venereology》2010,24(11):1270-1277
Psoriasis is commonly associated with a co‐existent arthritis known as psoriatic arthritis (PsA). Although there is some treatment overlap for psoriasis and psoriatic arthritis, it is possible that dermatologists may not diagnose or treat appropriately patients who are developing psoriatic arthritis at an early stage of the disease process when joint damage may be preventable. In this article we review the criteria for diagnosis of this sero‐negative arthritis, look at the clinical indications for referral to a rheumatologist and discuss evolving treatment options relevant to both conditions. 相似文献
35.
36.
New quinolones--a fresh answer to the pneumococcus 总被引:1,自引:0,他引:1
37.
38.
Tang RB Wang HY Lu HY Xiong J Li HH Qiu XH Liu HQ 《第二军医大学学报》2005,26(8):880-880
There have been extensive observations that RNA containing repetitive elements accumulates in transformed cells and tumor tissues. In the present study, we first obtained result consistent with previous observations by in situ hybridization. 相似文献
39.
Khan RB Boop FA Onar A Sanford RA 《中国神经肿瘤杂志》2006,4(2):142-142
OBJECT: The goals of this study were to define the incidence of seizures in children with low-grade tumors, study seizure outcome after lesionectomy in these children, and identify risk factors for poor seizure outcome, METHODS: The authors performed a retrospective chart review of children who harbored low-grade brain tumors, experienced seizures, and were treated in a single institution, Statistical analyses included step-wise as well as single-variable binary logistic regression analyses. 相似文献
40.
Ki-ras mutations are an early event and correlate with tumor stage in transplacentally-induced murine lung tumors 总被引:2,自引:2,他引:2
Leone-Kabler S; Wessner LL; McEntee MF; D'Agostino RB Jr; Miller MS 《Carcinogenesis》1997,18(6):1163-1168
A previous study from this laboratory demonstrated that treatment of
pregnant mice with 3-methylcholanthrene (MC) caused lung tumors in the
offspring at 1 year after birth, the incidence of which correlated with
fetal inducibility of Cyp1a1. Analysis by PCR amplification and allele-
specific hybridization (ASO) of paraffin-embedded tumors generated from
that study revealed the presence of point mutations in exon 1 of the Ki-
ras gene. This work has now been expanded by PCR amplification and ASO
analysis of 31 additional lesions. Point mutations were found in 37 of the
47 (79%) lesions analyzed in this and the previous study, the majority of
which were G-->T transversions in the first or second base of codon 12.
The mutational spectrum appeared to be dependent on the relative stage of
differentiation of the lesion, as both the incidence of mutation and type
of mutation produced correlated with malignant progression. Mutations
occurred in 60% of the hyperplasias, 80% of the adenomas and 100% of the
adenocarcinomas. In the lesions with mutations, GLY12-->CYS12
transversions occurred in 100% of the hyperplasias, 42% of the adenomas and
14% of the adenocarcinomas. The GLY12-->VAL12 transversions occurred in
none of the hyperplasias, 42% of the adenomas and 57% of the
adenocarcinomas. The remaining mutations, which consisted of ASP12
transitions and ARG13 transversions, occurred only in adenomas (17%) and
adenocarcinomas (29%). Between this study and our previous analyses, the
identity of the mutations obtained by ASO were confirmed by sequence
analysis of eight of the 37 lesions that harbored mutations at the Ki-ras
gene locus. There were no differences in the type or incidence of mutations
relative to the metabolic phenotype or sex of the mice. These data suggest
that mutational activation of the Ki-ras gene locus is an early event in
transplacental lung tumorigenesis, and that the type of mutations produced
by exposure to chemical carcinogens can influence the carcinogenic
potential of the tumor. This may have prognostic significance in
determining the malignant progression of the neoplasm.
相似文献