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Biomedical subjects

K Nilsson

Publications and source records attributed to K Nilsson.

At least 343 records · Page 19Linked to original sources

Accessory function of human tumor cell lines. I. Production of interleukin 1 by the human histiocytic lymphoma cell line U-937.

The established human histiocytic lymphoma cell line U-937 spontaneously produced a factor with biological activity similar to that ascribed to interleukin 1 (IL 1). Actually, supernatants from U-937 cells promoted proliferation of thymocytes initiated by concanavalin A (Con A) and replaced the requirement of accessory cells for activation of highly purified circulating T lymphocytes induced by Con A. Phorbol myristate acetate (PMA) significantly increased the titers of the helper factor produced by U-937 cells as compared to that secreted by non-PMA-treated U-937 cells or PMA-stimulated P388D1 murine macrophage tumor cells. Generally U-937 cells did not secrete detectable IL 1 activity during the first 24-48 h of culture. However, after this initial period the level of IL 1 activity increased and reached a maximum at 5-6 days of culture. Finally, the helper factor released by U-937 cells had an apparent mol. wt. of 12000-15000 as determined by Sephadex G-100 chromatography and lacked interleukin 2 activity as shown by its inability to support growth of IL 2-addicted T cell lines. To our knowledge this is the first report of an established human cell line capable of producing IL 1.

Animals↗

Postoperative sore throat related to tracheal tube cuff design.

Recent reports of the incidence of postoperative sore throat following anaesthesia with tracheal intubation have claimed that low volume high pressure cuffs are preferable to those with high volume and low pressure. In this study similar methods were used for evaluating postoperative sore throat. Randomly selected tracheal tubes were used in 56 patients undergoing elective abdominal surgery, followed by direct questioning about sore throat on the first postoperative day. The incidence of postoperative sore throat was 41 per cent with high volume low pressure cuffed tubes and 55 per cent with low volume high pressure cuffed tubes. This difference is not statistically significant, but the tendency of the results is contradictory to those published earlier. The incidence of postoperative sore throat varies greatly if direct or indirect questioning is used and also varies between studies using the same method of questioning. Therefore the validity of this method for evaluating the influence of cuff design must be questioned. Postoperative sore throat is a symptom caused by many factors, such as the intubation procedure and the use of stylets or lubricants. The incidence of postoperative sore throat does not necessarily reflect damage caused by the tracheal tube cuff.

Anesthesia↗

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↗

Neuron specific enolase: a marker for differential diagnosis of neuroblastoma and Wilms' tumor.

Thirteen human neuroblastoma and six Wilms' tumor biopsies have been analyzed for neuron specific enolase (NSE). THe relative activity of NSE in the neuroblastomas (including ganglioneuroblastoma and ganglioneuroma) ranged from 28% to 62.5% of total enolase activity. The corresponding figures for the Wilms' tumors were 1% to 4.5%. It appears that NSE can serve as a biochemical marker for neuroblastoma and be useful in the differential diagnosis of neuroblastoma and Wilms' tumor.

Child↗

Radiosensitivity of human B-lymphocytic lymphomas in vitro.

The radiosensitivity of four human B-lymphocytic lymphoma cell lines has been studied. For all lines the Do values were in the range 1.3 to 1.8 Gy. None of the survival curves had an appreciable shoulder. The extrapolation numbers varied in the range 1.0 to 1.2. Thus, the cell lines had a low capacity to accumulate sublethal damage. Furthermore, split dose experiments showed that no line had the capacity to repair sublethal damage. Taken together with earlier published experimental and clinical observations the results indicate that the use of an increased number of fractions in radiotherapy of B-lymphocytic lymphomas might be of great benefit to the patients. A schedule with an increased number of fractions will probably be as efficient in killing the tumour cells as previously used schedules but the tolerance of adjacent normal tissue will probably increase.

B-Lymphocytes↗

Synthesis of thromboplastin by U-937 cells.

A human monocytoid cell line (U-937) produces a procoagulant identified as thromboplastin when stimulated with phytohaemagglutinin (PHA), endotoxin, immune complexes, the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) or the divalent ionophore A 23187. The basal thromboplastin expression of these cells and the increased activity induced by the stimulants were dependent on supply of fresh medium suggesting that the synthetic rate was highest when the cells were in logarithmic growth. Inducible thromboplastin synthesis was inhibited by actinomycin D or cycloheximide, indicating dependence on messenger RNA and protein synthesis. Differentiation of the cells in the macrophage direction by TPA did not make the cells more responsive to PHA. Thromboplastin induction in U-937 cells was potentiated by the presence of lymphocytes, especially when stimulated with PHA or endotoxin. This supporting effect was also obtained by conditioned medium from lymphocyte cultures, suggesting a role for a soluble lymphocyte product.

Antigen-Antibody Complex↗

Natural killer (NK) cell sensitivity of phorbol ester-differentiated tumour cells correlates with disease activity in chronic B-lymphocytic leukaemia.

In a prospective study, 16 patients with chronic B-lymphocytic leukaemia (CLL) were repeatedly investigated for clinical and laboratory signs of disease activity during a period of 18 months. The leukaemic cells were induced to differentiate in vitro using a phorbol ester, TPA. Two differentiation-associated properties of the tumour cells, i.e. the amount of cytoplasmic immunoglobulin (C-IgM) and the increased sensitivity to lysis by natural killer (NK) cells, were expressed in parallel and both parameters were positively correlated with the clinical activity of leukaemia. Phorbol ester-induced phenotypic changes of the leukaemic cells may therefore be used for the in vitro monitoring of disease activity in CLL. The present markers may, in addition, be useful in molecular analysis of B cell differentiation.

Adult↗

An oxygen-consuming model lung for evaluation of anaesthetic circuits.

We have constructed an oxygen-consuming model lung based on pure combustion of hydrogen. Besides consuming oxygen the model produces water vapour, and carbon dioxide is delivered to the lung, thus mimicking carbon dioxide production. Oxygen consumption and carbon dioxide production can be set at desired values. The model lung can be used for investigations on and evaluation of all types of anaesthesia circuits. Results in a circle system with carbon dioxide absorption show that FIO2 is related to the fresh gas flow. The end tidal CO2 level is correlated to the alveolar ventilation and cannot be used for predicting FIO2.

Anesthesiology↗

Identification of a chemokinetic inhibitor in serum from patients with chronic lymphocytic leukaemia.

The effects of serum from patients with chronic lymphocytic leukaemia (CCL) on normal polymorphonuclear leucocyte migration (PMN) were examined by means of the leading front technique, using a modified Boyden chamber. 18 randomly selected patients were studied. 13 patients had a reduced chemokinetic activity. The defective migration was explained by the finding in serum from these patients of cell-directed inhibitory activity which was destroyed by heating (56 degrees C, 30 min). The B-lymphocytes as the origin of the inhibitory activity was suggested by the presence of a similar activity in supernatants from cultured tumour cells. 6 of the 18 patients had the combination of a defective chemokinetic activity and low levels of immunoglobulins. These 6 patients had an increased tendency towards infections.

Aged↗

Establishment and characterization of two neoplastic cell lines (U-1285 and U-1568) derived from small cell carcinoma of the lung.

Two human cell lines have been established in vitro from patients with small cell carcinoma of the lung (SCC). The U-1285 line was derived from the classical small cell type of SCC while the U-1568 originated from a larger cell variant. The cell lines grow as suspension cultures and have been passaged continuously in vitro for 3 years (U-1285) and 2 years (U-1568), respectively. The malignant nature of the lines is suggested by their infinite growth potential, their capacity to form colonies in agarose and their aneuploidy. Both cell lines contain cytoplasmic electron dense particles indistinguishable from classical neurosecretory granules but only in U-1568 has hormone production (human chorion gonadotropin (alpha-HCG)) been proven. The U-1568 line produces carcino-embryonic antigen (CEA) while both U-1285 and U-1568 produce alpha-feto-protein (AFP). Chromosome analysis reveal aneuploidy of both lines. Among structural aberrations, involvement of chromosome 14 in U-1285 and chromosomes 1, 7 and 12 in U-1568 is interesting since alterations of these chromosomes have been described previously in other malignant conditions.

Carcinoma, Small Cell↗

Polyacrylamide microbeads with entrapped protein A from S. aureus for cell separation.

A technique was developed for the identification and separation of cells according to their surface antigenic markers, based on immobilization of protein A by entrapment in polyacrylamide microbeads. This method is further development of the previous techniques with SpA-containing S. aureus bacteria, but has the advantage of having less unspecific binding to the cells. We show that this technique might be a useful tool for the separation of cells, exemplified by separation of cells on Petri dishes coated with a monolayer of SpA-microbeads. The viability of separated cells was unaffected and adherent cells were easily removed by trypsin.

Acrylic Resins↗

Cyclosporin-A is selectively cytotoxic to human leukemic T cells in vitro.

We have studied the antileukemic effects of cyclosporin-A (CyA) on the cells of a number of human hematopoietic biopsies and established cell lines in vitro. Cya killed the tumor cells but not the nonmalignant control cells from three of four patients with T-lymphocytic leukemia/lymphoma at concentrations comparable to those recommended in clinical long-term immunosuppressive therapy. The leukemic cells from 7 patients with B-type chronic lymphocytic leukemia were insensitive to CyA. The drug was cytostatic and cytolytic to three of five T-lymphoblastic leukemia cell lines tested. With the possible exception of a plasma cell line, all other control cell lines (B-lymphocytic lymphoma, histiocytic lymphoma, fibroblast, and glia cell lines) were resistant to CyA. These observations indicate that CyA or its derivatives may be useful as a highly selective antitumor agent in different T-cell malignancies.

B-Lymphocytes↗

Phenotypic changes of human neuroblastoma cells in culture induced by 12-O-tetradecanoyl-phorbol-13-acetate.

SK-N-SH and SH-SY5Y human neuroblastoma cells treated by 12-)-tetradecanoyl-phorbol-13-acetate(TPA) express morphological and biochemical changes, which indicate that differentiation towards more mature cells has occurred. The most prominent morphological changes were the development in 40-60% of the cells of cell-surface projections longer than 50 micrometers and cytoplasmic neurosecretory granules demonstrated by electron microscopy. At the biochemical level, TPA induced a two-fold increase in the relative activity of neuron-specific enolase and 30- to 40-fold increase in noradrenaline and adrenaline concentrations. A decrease in proliferation rate of TPA-treated cells was observed. The biological effects of TPA were slightly potentiated by nerve growth factor.

Cell Division↗

Neuron-specific enolase in relation to differentiation in human neuroblastoma.

The presence of the two forms of enolase, neuron-specific enolase (NSE) and non-neuronal enolase (NNE), have been examined in biopsy material of human neuroblastoma, ganglioneuroblastoma, ganglioneuroma and cultured neuroblastoma cells, after separation with ion exchange chromatography. The enolase activities were inhibited in the presence of NaCl but remained active in KCl, which were used in the chromatographic step. The relative NSE levels in the neuroblastoma tissues were found to be lower than in the histopathologically more differentiated forms of the tumour, i.e. ganglioneuroblastoma and ganglioneuroma. The human neuroblastoma in vitro cell lines SK-N-SH, SH-SY5Y, SK-N-MC and IMR-32 contained considerably lower relative levels of NSE compared to the levels in the neuroblastoma biopsies. After treatment of the cultured cells with nerve growth factor or dibutyryl-cAMP some cells showed morphological differentiation and concomitantly an increase in the NSE levels. The results indicate that NSE might be useful as a marker for differentiation in human neuroblastoma.

Biopsy↗

Diploid human lymphoblastoid and Burkitt lymphoma cell lines: susceptibility to murine NK cells and heterotransplantation to nude mice.

Human lymphoid cell lines which had been classified on the basis of studies on clonality and morphological, on the basis of studies on clonality and morphological, chromosomal and functional parameters as lymphoblastoid cell line (LCL) of presumed non-neoplastic origin and Burkitt lymphoma (BL) lines of proven malignant origin, were tested for susceptibility to natural killer (NK) cells obtained from the spleens of athymic nude mice. The 20 lines included normal diploid LCL and aneuploid BL lines. All cells carried the Epstein-Barr virus (EBV) genome. In addition, two EBV-negative BL lines were tested. The pronase-induced release of 14C-DNA from 14C-thymidine-labelled target cells was used to assess the sensitivity of the cell lines to NK activity. When attempts were made to correlate the growth of the EBV-positive LCL and the EBV-positive BL cell lines in the subcutaneous space of adult nude mice with their susceptibility to NK cells, no significant correlation was observed. The EBV-negative BL cell line, Ramos, however, could be transplanted subcutaneously in nude mice and was more resistant to NK activity than was the EBV-negative BL cell line, BJAB, which cannot be transplanted subcutaneously. Growth of heterotransplanted EBV-converted cell lines in the subcutaneous space of adult nude mice may be influenced by immune effectors other than NK cells.

Animals↗

Lysis of human B-lymphocyte-derived lymphoma/leukemia cells of established cell lines by interferon-activated natural killer (NK) cells.

Cultured cell lines derived from malignant Epstein-Barr virus (EBV)-negative B cells, and representative of the more common types of naturally occurring non-Hodgkin lymphomas and related leukemias, were found to be sensitive to lysis by human natural killer (NK) cells. The observed lysis of such cell lines was mediated by a population of interferon-augmentable, FcR-positive, non-adherent lymphoid cells, which were also able to kill the "standard" NK targets K562 and Molt-4. When the NK susceptibility of the neoplastic, EBV-negative B cells was compared to that of diploid, EBV-carrying, non-neoplastic B lymphoblastoid cell lines (BLCLs) and of the "standard" NK target K562, several distinct patterns were observed. The killing of the neoplastic B cell lines was significantly less than that of K562, but significantly greater than that of the EBV-derived BLCLs of non-neoplastic origin. An additional finding was a similar NK susceptibility profile for the neoplastic, true histiocytic cell line U-937 (i.e., K562 greater than U937 greater than BLCLs). Furthermore, all cell lines, with the exception of the BLCLs, could effectively compete for the observed killing in cold target inhibition assays. The implications of these findings are discussed in relation to both neoplastic and non-neoplastic targets of NK lysis.

B-Lymphocytes↗