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- Bergh, Gösta, et al.
(författare)
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Altered expression of the retinoblastoma tumor-suppressor gene in leukemic cell lines inhibits induction of differentiation but not G1-accumulation
- 1997
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Ingår i: Blood. - 1528-0020. ; 89:8, s. 2938-2950
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Tidskriftsartikel (refereegranskat)abstract
- The retinoblastoma tumor-suppressor gene, RB, has been implicated in tumor suppression, in regulation of the cell cycle, and in mediating cell differentiation. RB is necessary for hematopoiesis in mice, and aberrant RB-expression is associated with the progress and prognosis of leukemia. We have used antisense oligonucleotides, established clones stably expressing an antisense RB construct, and also established clones over expressing the retinoblastoma protein (pRb) to study the role of RB expression in monocytic differentiation induced by all-trans retinoic acid (ATRA) or 1-alpha-25-dihyroxycholecalciferol (Vit D3) in the monoblastic cell line U-937 and erythroid differentiation induced by transforming growth factor beta1 (TGFbeta1) and hemin in the erythroleukemic cell line K562. A reduction in pRb production in antisense RB-transfected U-937 clones was shown. Antisense oligonucleotides as well as expression of the antisense RB construct suppressed differentiation responses to ATRA or Vit D3, as judged by the capability to reduce nitro blue tetrazolium, by the appearance of monocyte-related cell surface antigens and by morphologic criteria. K562 cells showed decreased differentiation response to TGFbeta1, but not to hemin, when incubated with antisense oligonucleotides. U-937 antisense RB-transfected cells were also suppressed in their ability to upregulate levels of hypophosphorylated pRb when induced to differentiate. Although U-937 cells incubated with antisense oligonucleotides and clones expressing the antisense RB construct were hampered in their ability to differentiate on incubation with ATRA or Vit D3, the induced G0/G1-accumulation was similar to differentiating control cells treated with ATRA or Vit D3. Intriguingly, U-937 clones overexpressing RB were also inhibited in their differentiation response to ATRA or Vit D3 but not inhibited in their ability to respond with G0/G1 accumulation when induced with these substances. The results indicate that pRb plays a role in induced differentiation of U-937 cells as well as K562 cells involving mechanisms that, at least partially, are distinct from those inducing G1 accumulation.
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| 2. |
- Ehinger, Mats, et al.
(författare)
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Expression of the p53 tumor suppressor gene induces differentiation and promotes induction of differentiation by 1,25-dihydroxycholecalciferol in leukemic U-937 cells
- 1996
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Ingår i: Blood. - 1528-0020. ; 87:3, s. 1064-1074
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Tidskriftsartikel (refereegranskat)abstract
- Leukemic U-937 cells, which lack normal p53, were stably transfected with a temperature-sensitive mutant of p53 to investigate the consequences for growth and differentiation. On induction of wild-type p53 activity at the permissive temperature, some of these cells underwent maturation as judged by the capacity for oxidative burst and the appearance of monocyte related cell surface molecules. Moreover, wild-type p53-expressing cells were more sensitive than p53-negative control cells to induction of differentiation by 1,25-dihydroxycholecalciferol; a twofold to fourfold increase of the fraction of cells showing signs of terminal maturation was observed when wild-type p53-expressing cells were incubated with 1,25-dihydroxycholecalciferol at concentrations that only slightly affected control cells. Whereas wild-type p53 activity per se induced maturation of certain cells, other underwent cell death judging from the reduced capability to exclude trypan blue and the appearance of fragmented DNA in flow cytometric analysis. The p53-induced cell death could be inhibited by incubation with 1,25-dihydroxy-cholecalciferol, but not all-trans retinoic acid. Thus, 1,25-dihydroxycholecalciferol, seemed to increase the survival of wild-type p53-expressing cells and to cooperate with wild-type p53 to induce differentiation. The data imply that p53-mediated maturation in U-937 cells depends on optimal regulation of signals for differentiation, survival and proliferation, and suggest a role for p53 in the differentiation induction of leukemic cells.
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| 3. |
- Ehinger, Mats, et al.
(författare)
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Involvement of the tumor suppressor gene p53 in tumor necrosis factor-induced differentiation of the leukemic cell line K562
- 1995
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Ingår i: Cell Growth and Differentiation. - 1044-9523. ; 6:1, s. 9-17
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Tidskriftsartikel (refereegranskat)abstract
- The cDNA of the human wild-type p53 tumor suppressor gene was constitutively overexpressed in the leukemic cell line K562 (which lacks detectable amounts of p53 protein) in order to investigate the consequences for growth and differentiation. Several stable clones were established by transfection of the expression vector pc53SN3. Expression of p53 protein was characterized by biosynthetic labeling and immunoprecipitation with the monoclonal antibodies pAb 1801 (reacting with wild-type and mutant human p53), pAb 240 (reacting with mutant human p53) and pAb 1620 (reacting with wild-type human p53). All clones which were 1801+, 240-, 1620- or 1801+, 240-, 1620+ were defined as "wild-type-like p53-expressing" clones. Our results show that expression of p53 protein is compatible with continuous proliferation of K562 cells. The growth characteristics of wild-type-like p53-expressing clones did not differ from that of control clones. However, the former were more sensitive than p53-negative control clones to growth inhibition by tumor necrosis factor (TNF), a cytokine with a potential role in growth and differentiation of myeloid leukemic cells. In addition, a 2- to 4-fold increase of the amount of hemoglobin, a marker of erythroid differentiation, was observed when wild-type-like p53 protein-expressing clones were incubated with TNF. This suggests that differentiation is the mechanism responsible for the increased TNF sensitivity of these clones. Our results support a role for p53 in mediating growth inhibitory and differentiation inducing signals by TNF.
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| 4. |
- Ehinger, Mats, et al.
(författare)
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p53-dependent and -independent differentiation of leukemic U-937 cells : relationship to cell cycle control
- 1998
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Ingår i: Experimental Hematology. - 1873-2399. ; 26:11, s. 52-1043
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Tidskriftsartikel (refereegranskat)abstract
- Observations based on overexpression of the suppressor gene p53 or interference with endogenous p53 support a role for p53 in mediating not only growth inhibition and apoptosis but also differentiation. The aim of this study was to characterize the mechanisms of p53-dependent differentiation in the monoblastic leukemia cell line U-937. These cells were transfected with a mutant of the p53 gene expressing wild-type p53 at a permissive temperature. The results showed that wild-type p53 and interferon (IFN)-gamma were able to work synergistically to promote differentiation. This cooperative response was not associated with early G1 arrest of the cell cycle, indicating that p53 can mediate differentiation by mechanisms other than those used for mediating G1 arrest. The differentiation response to transfected p53 with or without INF-gamma was inhibited by cyclic adenosine monophosphate (cAMP)-inducing agents (dibutyryl cyclic adenosine 3':5'-monophosphate, forskolin, and 3-isobutyl-1-methylxanthine) in a dose-dependent manner. In contrast, the differentiation response of p53-negative U-937 cells to 1,25-dihydroxychole-calciferol or all-trans retinoic acid was enhanced by cAMP-inducing agents at optimal concentrations and inhibited at higher concentrations. In addition, 1,25-dihydroxycholecalciferol-mediated differentiation could be achieved in cells arrested in G1 by concomitant incubation with cAMP-inducing agents, indicating that differentiation can occur in the absence of proliferation. In conclusion, the results of this study indicate that p53-dependent and -independent differentiation can occur independently of cell cycle regulation.
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| 9. |
- Gullberg, Mats, 1953-
(författare)
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Health care professionals' self description
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the present thesis was to survey and analyse professional self of health care professionals, focusing on perceptions of self, and on their attitudes towards aspects of sense of responsibility.Studies were accomplished with quantitative techniques using questionnaires and/or instruments. A total of 803 respondents was included, and the first study (I) presented the development of the PSDF and comprised 30 registered nurses. The next study (II) examined results from 332 medical laboratory technologists who answered the PSDF. In the third study (III) 68 occupational therapists responded to the PSDF. The fourth study (IV) was a six-year follow-up of 43 registered nurses from the beginning of their training to three years after graduation, and they responded to the PSDF, the SRF and to the Form for ranked sources of encouragement. The fifth study (V) comprised four professional groups from a university hospital in Sweden (physicians, physiotherapists, registered nurses and enrolled nurses), and 312 responded to the set of forms (the PSDF, the SRF, and the Form for ranked sources of encouragement).The main theoretical approach was based on symbolic interactionism, where the self is a significant notion. Concepts on attitude, sense of responsibility and encouragement were important.The results showed that there are components of self description that is 'specific to one professional group, but also components that uncover similarities. Three important components of professional self were outlined; professional conduct, work ability and empathy. Important issues were also encouragement for work done, which influences the professional self, and that the positive attitudes to sense of responsibility showed similarities with characteristics of professional self.In conclusion, two propositions were addressed: that professionals' self description is composed of three meaningful dimensions; professional conduct, work ability and empathy, and that the professional self can be improved throughdevelopment of intrinsic attitudes and behaviours.
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| 10. |
- Götherström, Christine, et al.
(författare)
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Development of a tool for measuring the concept of good care among patients and staff in relation to Swedish legislation
- 1995
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Ingår i: International Journal of Nursing Studies. - 0020-7489 .- 1873-491X. ; 32:3, s. 277-87
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Tidskriftsartikel (refereegranskat)abstract
- An instrument for measuring the concept of good care, in relation to the Swedish Health and Medical Services Act, has been developed and tested in short-term care. The instrument comprises 14 statements on good care. The construct validity was estimated by factor analysis based on the results from 240 patients. Five factors explained 62% of the variance of the 14 variables and covered the following areas: information, security, accessibility, continuity, and influence and respect. Patients (n = 240) and registered nurses (n = 57) showed differences in estimations of the concept of good care on all factors. There were only minor differences, however, within the patient group and the nursing group, respectively, on comparing the two samples. The instrument needs further testing in different care conditions.
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