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Biomedical subjects

K Nilsson

Publications and source records attributed to K Nilsson.

At least 289 records · Page 16Linked to original sources
PubMed1986

Role of iron in the proliferation of the established human tumor cell lines U-937 and K-562: effects of suramin and a lipophilic iron chelator (PIH).

Suramin was used to analyze the growth-effects of blockade of iron uptake on two established human cell lines, U-937 (monocytoid) and K-562 (erythroleukemic). Suramin suppressed cell surface transferrin (Tf) binding and uptake of iron via inhibition of receptor-mediated endocytosis (RME). As a result, both lines accumulated in the S-phase. DNA synthesis and cell division were inhibited in the suramin-treated U-937, but not in K-562. Iron, supplied by a route alternative to Tf-to suramin-suppressed U-937 cells, reinitiated DNA synthesis and cell division, although at a lower level than in control cells. Multiple effects on iron-dependent enzymes and an inhibition of binding of undefined growth factors necessary for the transition through the cell cycle are suggested to be mechanisms by which suramin affects the U-937 cells. The results imply that clinically observed side effects of suramin may be caused by interference with cellular iron metabolism.

Cell Cycle↗
PubMed1986

Subcellular characterization of the transferrin-transferrin receptor and iron accumulating system of established human erythroid and monoblastoid tumour cell lines.

The organelles in two human tumour cell lines in culture - U-937 and K-562 - involved in the receptor mediated endocytosis (RME) of transferrin (Tf) were studied after isolation from homogenates by density gradient separation. They were also studied by electron microscopy after labelling of living cells with Tf coated colloidal gold particles. Three different Tf containing fractions with densities 1.038 (plasma membrane), 1.040 (light endosomes) and 1.051 g/ml (heavy endosomes) were identified. Ultrastructural studies of the distribution of gold label indicated that Tf was present in structures normally involved in RME of other ligands, probably including the recently identified "compartment of uncoupling of receptor-ligand complex" (CURL). The endocytosed iron was found to be rapidly transferred into the cytosol, as shown by density gradient centrifugation. Isoelectric focusing analysis showed that the iron mainly became bound in ferritin. In the hemoglobin synthesizing cell line K-562, however, iron was also inserted into hemoglobin. The finding that heavy and light endosomes process Tf suggests that Tf follows the same route as other ligands, including the epidermal growth factor and low density lipoprotein, in a presumed prelysosomal pathway, despite the fact that Tf does not dissociate from its receptor. Our findings are thus consistent with the notion that an endosome system similar to that in other types of RME is responsible for the cleavage and separation of iron from the carrier Tf.

Cell Line↗
PubMed1986

Expression of gamma-subunit of enolase, neuron-specific enolase, in human non-neuroendocrine tumors and derived cell lines.

The gamma-subunit of 2-phospho-D-glycerate hydrolyase, E.C. 4.2.1.11 (enolase), neuron-specific enolase (NSE), is present at high concentrations in neurons and neuroendocrine cells and has therefore recently been introduced as a marker for neuroendocrine tumors. By the indirect methods, immunocytochemistry and radioimmunoassay, NSE has been detected also in some nonneuroendocrine tumors, a finding that could reflect technical artifacts or the capacity for NSE expression in nonneuroendocrine tumor cells. This paper reports on the expression of NSE in human neuroendocrine and nonneuroendocrine tumor specimens and in a panel of permanent human cell lines, by using a direct (enzymatic) and an indirect (radioimmunoassay) method for determination of NSE. We detected NSE in all tested tumor specimens and neuroendocrine tumor cell lines and in a majority (21 of 24) of the nonneuroendocrine tumor cell lines. In general, neuroendocrine tumor specimens and derived tumor cell lines contained more NSE than the nonneuroendocrine tumor specimens and cell lines. However, some of the cultured hematopoietic cell lines (T leukemia and Epstein-Barr virus immortalized B lymphoblastoid cell lines) had NSE levels comparable to those found in some neuroblastoma and small-cell lung carcinoma cell lines. We conclude that NSE is not exclusively expressed in neuroendocrine tumor cells.

B-Lymphocytes↗
PubMed1985

Karyotypic characterization of established cell lines and short-term cultures of human lung cancers.

Karyotypic patterns were analyzed from the four major histopathologic groups of human lung cancer: small cell (SCC), squamous cell (SQC), large cell (LCC), and adenocarcinoma (ADC). The studies were performed on banded chromosomes from direct preparations of pleural fluids (one case of SQC and LCC, respectively) and on cell lines. All metaphases were aneuploid and showed highly rearranged chromosomes, with the exception of the direct preparation of the SQC, which was pseudodiploid. The number of marker chromosomes varied-from tumor to tumor. No consistent aberrations could be detected. Special attention was paid to chromosomes 3p-, which was earlier reported to be a characteristic marker chromosome for SCC. We could confirm the presence of that abnormality in two of our six SCC lines. However, we also found a 3p- in a primary SQC culture, in one LCC cell line, and in one ADC cell line. The breakpoint on 3p was not consistent. In some lines, numerical and structural changes of chromosomes #1, #12, #14, and #22 were also noteworthy, although none of these chromosome abnormalities seemed to be correlated to a certain histopathologic group.

Adenocarcinoma↗
PubMed1985

Immunocytochemical demonstration of neuron-specific enolase (NSE) in human lung cancers.

An anti-serum against human neuron-specific enolase (NSE), raised in sheep, has been characterized and used for immunocytochemical localization of NSE in paraffin sections of normal tissues and lung cancers. Of the small cell carcinomas (SCC), 69 out of 99 (70%) cases stained with the anti-serum. Maltreated biopsies showed a lower frequency of positive staining (19/39), indicating the importance of well-preserved biopsies. There was no clear difference in the staining between the oat cell and intermediate cell type of SCC. A majority (14 out of 21) of the non-SCC:s (large cell, adenocarcinoma and squamous cell carcinoma) were also stained by the anti-serum. Generally, this staining was weak and it could be blocked by preabsorption of the anti-serum by purified NSE. It is concluded that NSE expression, in conjunction with traditional histology, serves as a useful but not exclusive marker for SCC.

Adenocarcinoma↗
PubMed1985

Effects of the rectal administration of diazepam. Diazepam concentrations in children undergoing general anaesthesia.

Diazepam 1 mg/kg body weight was administered rectally to 14 children (11-22.5 kg) before minor surgery under general anaesthesia. Administration in solution (n = 7) resulted in a rapid increase in serum concentrations which were maintained for 8 h. Administration by suppository (n = 7) resulted in significantly lower serum concentrations at 10 and 20 min, but higher concentrations at 2 h. At other intervals the concentrations did not differ from those reached after administration of diazepam in rectal solution. These results favour for use of a solution when rectal diazepam is used for premedication in children.

Anesthesia, General↗
PubMed1985

Nitrous oxide exposure during routine anaesthetic work. Measurement of biologic exposure from urine samples and technical exposure by bag sampling.

Nitrous oxide exposure in a modern hospital during routine anaesthetic work was measured using a technical exposure measurement technique and compared to measurement of biologic exposure from urine samples. The study included different anaesthetic situations and also a study of the efficiency of close scavenging and general air-conditioning in reducing nitrous oxide exposure. Exposure to nitrous oxide varied greatly. The mean nitrous oxide exposure in the total material was 53 ppm corresponding to approximately half the Swedish control limit (100 ppm) for 8 h time-weighted average (TWA). The only anaesthetic situation regularly resulting in 8 h TWA exposure exceeding the control limit was paediatric anaesthesia (92 +/- 67 ppm, mean +/- s.d.). The use of close scavenging significantly reduced the 8 h TWA nitrous oxide exposure in paediatric anaesthesia. The reduction of exposure was not significant during other forms of anaesthesia where low levels were found when anaesthetic equipment with excess gas scavenging was used in theatres with non-recirculating air-conditioning. The correlation between conventional technical exposure measurement and urine headspace nitrous oxide measurement was good. Both theoretical arguments and practical experience indicate that this method can be used for assessing nitrous oxide exposure during routine anaesthetic work.

Air Pollutants, Occupational↗
PubMed1985

The dynamic morphology of the transferrin-transferrin receptor system in human leukaemia/lymphoma cell lines and its relation to iron metabolism and cell proliferation.

Some functional and morphological aspects of the transferrin-transferrin-receptor (Tf-TfR) system were investigated in 12 human haematopoietic tumour cell lines. The iron uptake ability, studied by 59Fe labelling, varied considerably between individual tumour cell lines. The studies of the morphology of the Tf-TfR system by fluorescence based methods using labelling by FITC-Tf, and by indirect immunofluorescence (OKT9 anti-TfR monoclonal antibody) demonstrated that the iron uptake was the result of receptor-mediated endocytosis (RME) of the Tf-TfR complex. The RME was better developed in the haemoglobin synthesizing K-562 cells than in the monocytic U-937 cells, suggesting that the intracellular iron processing capacity differs from cell type to cell type. The efficiency of iron-uptake, transport and storage was related to cell growth. Inhibition of growth by increasing cell densities or by drug treatments (phorbol ester TPA and difluoromethylornithine DFMO) was thus accompanied by a decrease in surface Tf binding, in cellular Tf handling capacity and in iron accumulation. TPA induced a redistribution of the TfR-pool to the intracellular space as demonstrated by morphology.

Cell Division↗
PubMed1985

Correlation between in vitro and in vivo sensitivity to human leucocyte interferon in patients with multiple myeloma.

26 of 32 patients with multiple myeloma (MM) were successfully tested in vitro for human leucocyte interferon (IFN) sensitivity by use of the human tumour stem cell assay (HTCA) and/or 3H-thymidine incorporation (LI). Altogether, 12 patients were sensitive to IFN in vitro and 14 were resistant. All patients received treatment with leucocyte IFN. 8 patients were classified as responders, 3 as partial responders and 15 as non-responders. Correlating the in vitro/in vivo results, we found that the in vitro tests of the myeloma cells reflected a true sensitivity in 9 patients (75%) and a true resistance in 12 patients (86%). Furthermore, stimulation by IFN was found in 9 in vitro tests, of which 8 were obtained from non-responsive patients. Our results show that in vitro testing for IFN sensitivity is of clinical importance in predicting response to IFN treatment. Also, a stimulating effect by IFN in vitro will imply an unfavourable response in vivo.

Adult↗
PubMed1985

Establishment and characterization of cell lines from human small cell and large cell carcinomas of the lung.

Five new small cell carcinomas (SCC) cell lines and a large cell carcinoma (LCC) cell line were established from human lung cancers. The SCC cell lines had, as a group, common phenotypic properties which distinguished them from non-SCC cell lines. However, the studies also revealed a considerable biological heterogeneity among the individual SCC cell lines. Thus, the SCC cell lines had a typical growth pattern with cell clusters in suspension or partly adherent to the bottom. All the lines examined grew in agarose with variable cloning efficiencies, and all but one line formed tumors subcutaneously in nude mice. The ultrastructure of the SCC cell lines was characteristic with dense core granules at a variable frequency. Neuron-specific enolase was detectable in all SCC cell lines, usually in large amounts, and an inconstant production of a spectrum of polypeptide hormones was found, typical of SCC. The LCC cells proliferated in monolayers, formed colonies in agarose and grew in nude mice. Ultrastructurally, the LCC cell line differed from the SCC cell lines in having intra- and intercellular lumina and tonofilaments. The capacity of the LCC and a previously established squamous cell carcinoma cell line (U-1752) to produce neuron-specific enolase and polypeptide hormones was characteristically much lower than that of the SCC cell lines. We conclude from this study that SCC cell lines, although individually distinct from one another, are quite homogeneous as a group in expressing a set of basic common neuro-endocrine markers. However, these studies also suggest some biological relationship between SCC, LCC and SQC by virtue of their expression of some common neuro-endocrine markers, in support of the concept of a common histogenetic origin of human lung cancers.

Carcinoma, Small Cell↗
PubMed1985

Neurone specific enolase: a useful diagnostic serum marker for small cell carcinoma of the lung.

Among lung cancers small cell carcinoma is the most sensitive to chemotherapy and radiation. This has emphasised the importance of an accurate diagnosis of this cell type, and the present study examined the use of serum neurone specific enolase (NSE) as a diagnostic marker for small cell carcinoma. NSE was measured in pretreatment sera from 103 patients with small cell carcinoma and in sera from relevant controls, including patients with other lung cancers, non-malignant lung diseases, and healthy adults. Serum NSE concentration was raised (greater than 25 ng/ml) in 72% of patients with small cell carcinoma. Ninety one per cent of patients with extensive disease and 50% of patients with limited disease were serum NSE positive. Patients with extensive disease in general had higher serum NSE concentrations than patients with limited disease. No definite difference in serum NSE positivity could be shown between oat cell and intermediate cell subtypes. Out of 51 patients with other lung cancers, four (8%) had a raised serum concentration, whereas all patients with non-malignant diseases and healthy individuals had normal serum NSE concentrations. Serum NSE determination seems to be a valuable tool for the diagnosis of small cell carcinoma.

Adult↗
PubMed1985

Amplification of the c-myc oncogene in a subpopulation of human small cell lung cancer.

We have examined a panel of human lung cancer cell lines for amplification and expression of the c-myc, N-myc, and c-myb oncogenes. The cell lines analyzed represent various histopathological types of lung cancer: small cell carcinoma with neuroendocrine properties; squamous cell carcinoma with epithelial markers; and large cell carcinoma with a mixed neuroendocrine-epithelial phenotype. Two of six cell lines, both of which were small cell carcinomas, showed about a 20-fold amplification of the c-myc oncogene. In both cell lines, the amplification is accompanied by an enhanced expression of c-myc. The N-myc or c-myb genes were not amplified in any of the cell lines, nor were they expressed in detectable amounts. The results confirm and extend earlier findings on c-myc amplification in small cell lung cancer.

Carcinoma, Small Cell↗
PubMed1985

Phorbol ester-induced differentiation of chronic B lymphocytic leukaemia cells--regulatory impact of autologous and allogeneic accessory cells.

Phorbol ester (TPA) induction of chronic lymphocytic leukaemia (CLL) cells can be used as a model system for the study of human B cell differentiation. We have analysed the role of accessory cells and the correlation to target cell surface Ig phenotype in TPA-induced morphological and functional differentiation of 12 CLL populations. A more than three-fold increase in secreted IgM was seen in 10 of 12 cases, with the strongest responses in patients having monoclonal serum IgM. CLL populations negative for or having only weak surface mu chain expression were less inducible. The impact of autologous and allogeneic accessory cells on TPA induction was studied in cell enrichment/depletion experiments using both physical and cytotoxic antibody techniques. CLL cells physically depleted of autologous E+ and monocytic (light density fraction) cells still responded to TPA. This response could be enhanced by allogeneic E- light fraction cells. Further depletion of autologous accessory cells by treatment of the E- high density fraction CLL cells with a panel of monoclonal antibodies plus complement demonstrated the permissive role of one or two populations of autologous cells expressing low avidity E receptors and the T3, T4 and T8 antigens. Augmenting T cells of similar phenotype were found among allogeneic cells from normal individuals. Thus, TPA-induced IgM secretion in biopsy B-CLL cells is regulated by minute numbers of autologous helper T cells. Furthermore, the Ig secretory response of CLL populations seems to be correlated with the surface Ig the surface immunoglobulin phenotype of the leukaemic cells.

Aged↗
PubMed1985

Flow resistance of endotracheal tubes during kinking and compression. An experimental study.

Kinking and compression of endotracheal tubes may lead to serious problems. Such complications are assumed to occur more often for smaller endotracheal tubes used in adult practise in order to reduce to trauma of intubation. The effect of kinking and compression on the air-flow through PVC endotracheal tubes of various dimensions (inner diameter 6, 7, 8 and 9 mm) and types (manufactured by National Catheters, Portex and Shiley) has been studied in an experimental model. All tubes could be kinked surprisingly much before a measurable flow hindrance occurred. Only small differences were measured between different dimensions and types. In contrast smaller endotracheal tubes were considerable less resistant to edge compression than larger dimensions.

Equipment Design↗
PubMed1985

Phorbol ester-induced alteration of differentiation and proliferation in human hematopoietic tumor cell lines: relationship to the presence and subcellular distribution of protein kinase C.

The intracellular translocation of protein kinase C (PKC) from the soluble to the membranous fraction has been shown previously to correlate with biological activity of phorbol esters in several systems. In this paper, we describe that PKC translocation was a general phenomenon in all PKC containing cell types when five 12-O-tetradecanoylphorbol-13-acetate (TPA) responsive and nonresponsive hematopoietic tumor cell lines were investigated. The nonresponsive cell line U-266 contained undetectable levels of PKC. The dose of TPA required for translocation was similar to the TPA concentration necessary to suppress erythroid differentiation in K-562 cells and to induce macrophage differentiation in U-937 cells, but 100-fold higher than that required for suppression of proliferation in K-562 and U-937 cells. By contrast, PKC translocation and TPA induced proliferation inhibition exhibited a similar dose dependence in a subline of U-937 (U-937 RES) adapted to growth in the presence of 10(-9) M TPA. It is suggested that U-937 RES is deficient in a TPA dependent but PKC independent signal pathway.

Biological Transport↗
PubMed1984

[Neopterin, a new biochemical marker for clinical assessment of cell-mediated immune response].

Activated T-lymphocytes represent crucial effector cells. They are pathogenetically involved into various disease states such as allograft rejection or viral infection. So far their assessment is laborious and rarely possible in clinical routine. In this review article we present the compount neopterin as a new biochemical marker for the in vivo and in vitro detection of activated T-lymphocytes. Our main finding was that in vitro as well as in vivo stimulation of T-lymphocytes with foreign and chemically or virally modified autologous cells in invariably associated with increased neopterin production. It thus appeared that neopterin might represent a potential marker for biochemical monitoring of diseases caused by or associated with T-lymphocyte activation. Our clinical experience with neopterin determination in allograft rejection and in infectious or autoimmune states strongly support this view. We conclude that evaluation of neopterin represents a useful and simple tool for the biochemical monitoring of immunological and/or malignant states.

Adolescent↗