Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The conventional diffusion chamber (CDC) as described by Benestad (1970) had been modified to assay the colony forming capacity of RFM bone marrow and spleen cells in agar diffusion chambers (ADCs). The colonies are morphologically identical to those formed by the CFUc in agar culture in vitro and have an incidence of approximately 1 in 10(3) normal nucleated bone marrow cells, and 1 in 10(4) nucleated spleen cells. Comparison of the growth of normal bone marrow cells in CDCs and in ADCs suggests that cell proliferation in diffusion chambers may result from the same precursor cell as detected by colony formation in agar culture in vitro. This proposal is supported by the suicide of approximately 46% of the ADC colony precursor cells following incubation with (3)H-labelled thymidine.Colony formation by haemopoietic cells taken from leukaemic mice appears to be due to the proliferation of a remaining normal cell population alone, while the leukaemic cells in the inoculum form a background of uniformly distributed blast cells. In the case of leukaemic cell culture, there are differences in the results from CDCs and ADCs, and data from colonies in leukaemic ADC cultures are similar to those from normal ADC colonies. These comparisons imply that the ADC technique may be used to monitor the functional capacity of normal bone marrow, by its ability to form colonies, during the development of leukaemia. A humoral effect of a leukaemic environment on the growth of normal bone marrow cells in ADCs has also been detected.
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PMID:Quantitation of haemopoietic cells from normal and leukaemic RFM mice using an in vivo colony assay. 453

Low-density (less than 1.077 g/ml) marrow or blood cells from patients with acute or chronic leukemia release a high molecular weight substance called "leukemia-associated inhibitor" (LAI) that reduces the fraction of normal marrow CFU-c in S-phase as measured with the 3H-TdR suicide technique. LAI from conditioned media or 3M KCl extracts of subcellular fractions behaved homogeneously on gel chromatography, showing an apparent molecular weight greater than 500,000. However, ion-exchange chromatography and isoelectric focusing indicated considerable charge heterogeneity for LAI molecules. Results from SDS-polyacrylamide gel electrophoresis indicated that the biologic activity resides in a subunit of 150,000-170,000 daltons. The findings of marked affinity for Con-A-Sepharose, marked susceptibility to mild periodate treatment, partial susceptibility to protease digestion, and relative resistance to heating suggest that LAI is a glycoprotein. Data from radiolabeling of cell surface components and sucrose density gradient centrifugation are consistent with LAI being a peripheral cell membrane glycoprotein, which may suppress normal granulopoiesis in leukemia.
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PMID:Biochemical characterization of a leukemia-associated inhibitor (LAI) suppressing normal granulopoiesis in vitro. 624 96

A total of 3440 veterinary surgeons resident in Britain were followed up from 1949-53 until 1975. A roughly twofold increase in mortality from suicide was observed and also a decreased mortality from respiratory diseases. There was no excess of deaths from leukaemia or other cancers as recently reported from the United States and as implied by the hypothesis that veterinary surgeons are unusually exposed to oncogenic viruses.
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PMID:Mortality among British veterinary surgeons. 641 30

In the experimental rat leukemia system, induced by repeated 7,12-dimethylbenz(a)anthracene (DMBA) pulses, the sensitivity of the spleen colony-forming hematopoietic stem cells (CFU-s) to the cytocidal action of a challenging DMBA injection (35 mg/kg body weight) varied with the number of pulses already applied and the organ source of CFU-s (femoral bone marrow or spleen). Assessment of the fraction of DNA-synthesizing CFU-s with the [3H]thymidine suicide technique at the time of DMBA challenge and comparison with the 20-hr CFU-s reduction values by DMBA in vivo showed an inverse correlation (p less than 0.001). It was deduced, therefore, that S-phase CFU-s are relatively resistant to DMBA cytocide. Since initiation by chemical carcinogens has been shown to be relatively S-phase specific, S-phase-resistant cytocide would lead to a selection of initiated cells and, in the case of repeated applications, to a selection of cells with multiple successive initiation hits. Preferential differentiation and organ site of leukemia, as well as evolution in sequential morphological steps, fit this assumption.
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PMID:S-phase resistance of rat hematopoietic stem cells to 7,12-dimethylbenz(a)anthracene cytocide and its implications for leukemia development. 643 May 52

To evaluate the potential carcinogenic effects of formaldehyde, we examined the proportionate mortality experience of embalmers licensed to practice in California. Mortality was significantly elevated for total cancer, arteriosclerotic heart disease, and suicide, whereas significant deficits were noted in mortality from diseases of the respiratory and genitourinary systems. Deaths from cancers of the brain, colon, and prostate and leukemia were significantly higher than expected. No increased mortality was seen for cancers of the respiratory tract, including the nasal passages, where an effect might be expected based on animal studies. A parallel mortality survey of embalmers from New York State showed similar findings, with excesses of brain tumors, leukemia, colon cancer, arteriosclerotic heart disease, and cirrhosis. Further investigation is needed to determine whether any of these outcomes is related to formaldehyde exposure.
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PMID:Cancer and other causes of death among embalmers. 646 19

In South-East Scotland, 791 subjects treated with lithium for more than two months during 1967-76 were traced, using public and health service records; 751 were traced alive, 33 had died, and seven remained untraced. The standardised mortality rate was 2.83, and excess mortality was attributable to suicide (increased 36-times) and cardiovascular disease (increased 2.15-times); deaths from nephropathy, cancer or leukaemia were not increased. Comparison of the 33 deaths and 33 matched patients, selected from the 751 survivors, showed that patients dying on lithium were similar in most respects to survivors, but when first starting lithium, they had more signs of physical disease.
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PMID:Mortality of a lithium-treated population. 647 21

The generally accepted cell-killing effect of hydroxyurea (HU) on S-phase cells, as well as its potential to arrest cells at the G1/S boundary, hardly explain its benefit for application in human chronic myelogenous leukaemia. Studies were therefore performed in rat haemopoiesis in order to quantify the cell-killing effect on various phases of the cell cycle. For this purpose, the [3H]thymidine [( 3H]TdR) labelling index and the specific activity of [3H]TdR in the DNA-synthesizing fraction of cells were determined after a non-cytoreductive dose of 25 mg/kg HU, as well as a medium cytoreductive dose of 100 mg/kg. Furthermore, flow cytometric DNA histograms and absolute as well as differential cell counts of femoral bone marrow were performed after 100 mg/kg HU. The results indicate a predominant cell kill in G1 encompassing almost all 2c cells in the proliferative pool, while the S-phase fraction is not even reduced to half its initial value. The specific activity of [3H]TdR in cells synthesizing DNA, as well as the labelling index after HU show an initial dip and a tendency to recovery, as has been observed in many other cell systems. Instead of a complete restoration, however, there is a second depression of these parameters lasting for at least one cell cycle. The results are interpreted as a partly cell-cycle-dependent and partly independent action of HU in this cell system. The independent component may be attributed to the repeatedly described direct interference of HU with DNA. In rat haemopoiesis, therefore, this direct effect of HU on the DNA strands appears to be much more pronounced than in cell-culture systems and other mammalian tissues. In view of these findings, some caution should be taken in using HU for the determination of the S-phase fraction by way of a suicide experiment.
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PMID:Cell-cycle-dependent and -independent damage to rat haemopoiesis by hydroxyurea. 648 79

Previous studies have indicated that the generation time of human leukaemic cells is longer than that of normal haematopoietic cells. We have employed a modification of the thymidine (TdR)-suicide technique to measure directly the generation time of leukaemic progenitor cells capable of colony formation. The results obtained with two human leukaemic cell lines (KG-1 and HL-60) and with blast progenitor cells from two patients with acute myelogenous leukaemia indicate generation times ranging from 9 X 0-22 X 0 hr and S-phase durations ranging from 5 X 5-8 X 0 hr. Using the same technique, the generation time of normal bone marrow CFU-c was determined to be 9-11 hr. These findings suggest that the proliferation rate of human leukaemic blast progenitor cells is similar to that of normal haematopoietic stem cells.
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PMID:Generation time of leukaemic blast progenitor cells. 657 75

We assayed the number of multilineage myeloid progenitor cells (CFU-GEMM) in the blood and marrow of patients with newly diagnosed chronic granulocytic leukaemia (CGL). The mean number of CFU-GEMM in the blood was increased 600-fold and CFU-GEMM in the marrow was doubled in the CGL patients compared with normal. A complement-fixing monoclonal antibody with HLA-DR specificity inhibited the proliferation of CFU-GEMM from CGL blood to a greater extent than that of comparable cells in normal marrow. Using a hydroxyurea 'suicide' method we found that the proportion of CFU-GEMM in proliferative cycle was higher in CGL blood than in normal marrow. We conclude that (1) CFU-GEMM numbers are greatly increased in the blood of patients with CGL, (2) CFU-GEMM express HLA-DR antigens on their surface, and (3) the apparently increased expression of the antigen on CFU-GEMM from CGL blood in comparison with CFU-GEMM from normal marrow may parallel the relatively higher proportion of CGL CFU-GEMM in cell cycle.
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PMID:Antigenic expression and proliferative status of multilineage myeloid progenitor cells (CFU-GEMM) in normal individuals and patients with chronic granulocytic leukaemia. 658 Jul 19

The infusion of donor lymphocytes after allogeneic bone marrow transplantation is a promising therapeutic tool for achieving a graft versus leukemia (GvL) effect in case of leukemic relapse (1-7), and for the treatment of other complications related to the severe immunosuppressive status of transplanted patients, such as Epstein Barr virus-induced lymphoproliferative disorders (EBV-BLPD) (8) or reactivation of CMV infection (9). Although the delay in the administration of T lymphocytes is expected to reduce the risk of severe GvHD, this risk is still present at higher doses of donor T-cells. The transfer of a suicide gene into donor lymphocytes could allow the in vivo selective elimination of cells responsible for severe GvHD. Additionally, under appropriate conditions, it may allow in vivo modulation of donor anti-tumor responses, and to separate GvL from GvHD. Finally, crucial questions concerning survival and function of donor lymphocytes could be answered by their gene marking. Previous studies documented that T lymphocytes are suitable targets for gene transfer through retroviral vectors (10, 11). This protocol has been designed to evaluate in the contest of allogeneic BMT: 1--the safety of increasing doses of donor lymphocytes transduced with a suicide retroviral vector; 2--the efficacy in terms of survival and immunologic potential of donor lymphocytes after in vitro activation, gene transduction, and immunoselection; 3--the possibility of in vivo down regulation of GvHD by the administration of ganciclovir to patients treated by tk-transduced donor lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transfer of the HSV-tk gene into donor peripheral blood lymphocytes for in vivo modulation of donor anti-tumor immunity after allogeneic bone marrow transplantation. 754 81


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