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Biomedical subjects

E Lundgren

Publications and source records attributed to E Lundgren.

At least 163 records · Page 9Linked to original sources

Growth-state independent induction of specific proteins in Swiss 3T3 cells by interferon.

The early effects of interferon (IFN) on the pattern of protein synthesis in Swiss 3T3 mouse fibroblasts were investigated by two-dimensional gel electrophoresis of 35S-methionine labeled cell extracts. IFN induced within 4 h the synthesis of three proteins with molecular weights of 48, 49, and 50 kD. An increase in the rate of synthesis of a 31 kD protein was also found. These changes were observed after IFN treatment of exponentially growing cells, density-inhibited cells, serum-starved cells, and serum-stimulated quiescent cells. The same protein patterns were obtained from cells treated with IFN-alpha or IFN-beta. The IFN response was blocked by the addition of actinomycin D, implying de novo transcription of the corresponding species of messenger RNA.

Animals↗

Interferon-specific effects on protein synthesis in P3HR-1 cells.

The effect of interferon (IFN) on protein synthesis was studied in the Burkitt's lymphoma cell line P3HR-1 by [35S]methionine labelling of the cells, followed by two-dimensional gel electrophoresis of cell extracts. De novo synthesis of three proteins (mol. wts. 33 000, 62 000, and 98 000, respectively) and alterations in the rate of synthesis for a small number of additional proteins were observed during the first 12 h of treatment, while the rate of overall protein synthesis was unaffected. Treatment of P3HR-1 cells with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or hydrocortisone (HC), which induce similar changes in cell cycle distribution as does IFN, did not induce comparable changes in the rates of protein synthesis. Thus, the effects were specific for IFN and not induced by the change in cell cycle distribution per se, i.e., accumulation in G0. Treatment of cells with 2'-5' pA core did not mimic the effect of IFN at the translational level. A substrain of P3HR-1 cells, selected for resistance to the anti-proliferative effect of IFN, lacked six proteins found in the wild-type. The 62 000 mol. wt. protein was induced in this substrain as well as in native P3HR-1 cells on addition of IFN. The resistant substrain still developed an anti-viral effect in response to IFN. Thus, it seems as if the anti-proliferative and anti-viral effects of IFN, at least in some cells are mediated by different intracellular molecular mechanisms.

Burkitt Lymphoma↗

Establishment and characterization of a human EBV-negative B cell line (MN 60).

A permanent cell line, MN 60, was established from the peripheral blood of a patient with an acute lymphoblastic leukemia (ALL) classified morphologically as being of the L3 type. Cell growth started rapidly in vitro and no feeder cells were needed. Cells of the MN-60 line were identical to the original leukemic cells with respect to surface immunoglobulin (Ig) expression and karyotype, including the presence of four marker chromosomes [1q+, 6q-, t(8;14)]. Continuous proliferation was maintained in stationary suspension culture with a doubling time of 25 h. The cells were tumorigenic in athymic nude mice and had the capacity to form colonies in semi-solid medium in vitro. Monoclonal surface Ig (mu lambda) was demonstrated whereas no cytoplasmic immunoglobulin could be demonstrated. The MN-60 cells were Epstein-Barr virus (EBV) negative as evidenced by EBNA tests and by nucleic acid hybridization studies. The cells expressed HLA-A-C, HLA-DR. beta 2-Microglobulin and cALL, but not Fc gamma. C3, sheep and mouse red blood cell receptors. No reactivity was found with anti-glycophorin A or the anti-BL 38.13 monoclonal antibody. Cell growth was retarded in the G0/G1 phase of the cell cycle after incubation with leukocyte interferon, hydrocortisone, phorbol myristate acetate and dimethyl sulphoxide.

Adult↗

The impact of growth pattern on survival in non-Hodgkin's lymphomas classified according to Lukes and Collins.

203 cases of non-Hodgkin's lymphomas assigned as follicle centre cell (FCC) type according to the classification of Lukes and Collins (1975) were analyzed according to growth pattern. Nodular cases had a better prognosis than diffuse ones even within a certain cell type. The abundance of parafollicular lymphocytes was a better criterium of nodularity than prominence of venules. Degrees of nodularity was best scored according to distribution of diffuse and nodular areas. Prognosis was better with a higher degree of nodular growth even within a certain cytological cell type. Therefore it is proposed that scoring according to different degrees of nodularity has a high prognostic impact and could be an alternative to scoring according to cell type within the group of follicle centre cell lymphomas.

Humans↗

B-cell growth factor: distinction from T-cell growth factor and B-cell maturation factor.

A T-cell hybridoma was derived by somatic cell hybridization between concanavalin A-activated BALB/c spleen cells and the AKR thymoma BW 5147. Media conditioned by hybridoma cells, even at high dilutions (1:1,000) support the growth of lipopolysaccharide-stimulated B-cell blasts but not that of T-cell growth factor (TCGF)-reactive T-cells. This activity, herein designated B-cell growth factor (BCGF), has a Mr of approximately equal to 20,000 and it can readily be separated from TCGF (Mr approximately equal to 30,000) by gel filtration. BCGF is constitutively produced by the hybridoma cells, it is removed from conditioned media by incubation with target cells at +4 degrees C, and it is equally effective on B-cell blasts carrying different major histocompatibility complex and Ig haplotypes. BCGF shows no T-cell replacing factor (TRF) activity, and it is poor in supporting the development of Ig-secreting plaque-forming cells in B-cell blast cultures. Terminal maturation, however, can be induced in BCGF-dependent blasts by addition of conditioned media from normal helper T cell cultures, suggesting that two distinct factors are involved in the helper cell-dependent growth and maturation of B lymphocytes.

Animals↗

Growth inhibition by IFN achieved by collecting cells in G0.

The P3 HR-1 cell line was studied with respect to sensitivity to the growth inhibitory properties of Hu IFN-alpha (leukocyte interferon). Cells growth arrested at high density and diluted into fresh medium, were growth inhibited at the same time and to the same degree as exponentially growing cells. Thus, resting cells did not seem to be more sensitive to IFN than exponentially growing cells. The cells displayed the same sensitivity to IFN during all cell cycle phases and they were found to enter the G0 stage in a dose dependent manner following first order kinetics.

Burkitt Lymphoma↗

Selective effects of interferon on distinct sites of the T lymphocyte triggering process.

Lectin- and antigen-induced proliferation of murine T cells consists of two major events, namely, a rapid induction of susceptibility to growth factors and a later-occurring, accessory cell-dependent production of T cell growth factors (TCGF). The mechanism by which interferon (IFN) inhibits T cell responses was studied accordingly. A decrease of Con A-induced proliferation was observed in the presence of increasing amounts of IFN. The reduced proliferative response in such cultures was found to be due to an accumulation of cells in the G0/G1 phase of the cell cycle. Furthermore, the results show that IFN did not inhibit the early events in T cell triggering, because the acquisition of responsiveness of resting T cells to TCGF was unaltered in the presence of IFN, nor did it interfere with production of TCGF. In contrast, IFN was found to interfere with the TCGF-dependent T cell blast growth. Cytofluorometric analysis of the proliferative phase revealed that IFN exerts its effect on T cells, which have entered the proliferative cycle, by a postmitotic accumulation in G0/G1, thus reducing the proliferating population. The results demonstrate that IFN primarily affects the later phase of proliferative activity after T cell triggering, leaving the helper cell functions untouched.

Animals↗

Rapid induction of seven proteins in human lymphocytes by interferon; correlation to natural killer cell activity.

The early effects of interferon (IFN) on the synthesis of protein in human nylon wool-nonadherent lymphocytes have been stimulated by use of two-dimensional electrophoresis. IFN-alpha or -beta as well as Escherichia coli-produced IFN-alpha 2 induced the rapid formation of seven proteins (Mr 80, 75, 62, 53, 38, 36, and 33 kD). At least five proteins were expressed within 2 hr of incubation with IFN. The synthesis of the seven proteins seemed to require rapid transcription of new RNA, because actinomycin D markedly inhibited their formation only when added less than 30 min after IFN. A good correlation was found between the ability of actinomycin D to inhibit both the formation of new proteins and the augmentation of natural killer (NK) cell activity. Screening of a panel of 10 hematopoietic and two anchorage-dependent cell lines revealed that p62 and p38 were induced in most cell lines, whereas p80 and p33 were preferentially induced in lymphoid cell lines. Three proteins could not be induced by IFN in any of the 12 cell lines, and thus could represent molecules mediating differentiated functions, possibly involved in NK cell function.

Blood Proteins↗

Copper- and zinc-containing superoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues.

Copper- and zinc-containing superoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase form the primary enzymic defense against toxic oxygen reduction metabolites. Such metabolites have been implicated in the damage brought about by ionizing radiation, as well as in the effects of several cytostatic compounds. These enzymes were analyzed in 31 different human normal diploid and neoplastic cell lines and for comparison in 15 normal human tissues. The copper- and zinc-containing superoxide dismutase appeared to be slightly lower in malignant cell lines in general as compared to normal tissues. The content of manganese superoxide dismutase was more variable than the content of the copper- and zinc-containing enzyme. Contrary to what has been suggested before, this enzyme did not appear to be generally lower in malignant cells compared to normal cells. One cell line, of mesothelioma origin (P27), was extremely abundant in manganese-containing superoxide dismutase; the concentration was almost an order of magnitude larger than in the richest normal tissue. Catalase was very variable both among the normal tissues and among the malignant cells, whereas glutathione peroxidase was more evenly distributed. In neither case was a general difference between normal cells and tissues and malignant cells apparent. The myocardial damage brought about by doxorubicin has been linked to toxic oxygen metabolites; particularly, an effect on the glutathione system has been noted. The heart is one of the tissues which have a low concentration of enzymes which protect against hydroperoxides. However, the deviation from other tissues is probably not large enough to provide a full explanation for the high doxorubicin susceptibility. In the present survey, no obvious relationship between generally assumed resistance to ionizing radiation or to radical-producing drugs and cellular content of any of the enzymes could be demonstrated.

Catalase↗

Block of glioma cell line in S by interferon.

The human glioma cell line U-251 MG, with a well-characterized defect in growth control, was sensitive to the antiproliferative effects of human (fibroblast) interferon (IFN). IFN inhibited exponentially growing cells by increasing the number of cells in the S stage of the cell cycle. At the same time the number of cells in Go/G1 diminished. The rate of thymidine incorporation was decreased during the first cell cycle, with no prolongation of S. However, in synchronized cultures, the wave of cells with a S-phase content did not decrease over a time period several hours longer than the length of S measured by pulse labelling. Thus we conclude that, at a sufficient dose, the cells were unable to accomplish cell division as they prematurely stopped synthesizing DNA.

Antineoplastic Agents↗

Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenols and phenoxy acids: a case-control study.

A number of men with malignant lymphoma of the histiocytic type and previous exposure to phenoxy acids or chlorophenols were observed and reported in 1979. A matched case-control study has therefore been performed with cases of malignant lymphoma (Hodgkin's disease and non-Hodgkin lymphoma). This study included 169 cases and 338 controls. The results indicate that exposure to phenoxy acids, chlorophenols, and organic solvents may be a causative factor in malignant lymphoma. Combined exposure of these chemicals seemed to increase the risk. Exposure to various other agents was not obviously different in cases and in controls.

2,4,5-Trichlorophenoxyacetic Acid↗

Human interferon for clinical trials: removal of pyrogen by a simple two-step procedure.

Commonly used preparations of human interferon are pyrogenic when used in humans for clinical trials. We describe a simple two-step procedure for the purification of human fibroblast interferon, employing Blue Sepharose chromatography and high-speed centrifugation. Such preparations are devoid of pyrogenic activity in a rabbit test system and are much more suitable for use in human clinical trials than previously used preparations.

Animals↗

Clinico-pathologic correlation in non-Hodgkin's lymphoma. IV. Analysis of patients with clinically localized disease.

A retrospective analysis of 140 patients with non-Hodgkin's lymphoma in clinical stage I or II classified according to a modified LUKES & COLLINS scheme was performed. Three major groups were found according to cell type, with different clinical features: (1) Small cell lymphomas with a relatively favourable survival in spite of high relapse rates. (2) Large cell lymphomas with lower relapse rates, but short time between relapse and death, and unfavourable survival. (3) Mixed small/large cleaved follicular centre cell lymphoma which was most favourable with respect to relapse and survival. Nodular lymphoma had the same overall relapse rate as diffuse lymphoma, but had a significantly longer survival. Tumours stage I were associated with significantly longer relapse-free survival and survival than stage II. The importance of separating the majority of non-Hodgkin's lymphomas into three main groups according to cell type is emphasized. These major groups require different clinical approaches in terms of staging and treatment.

Adult↗