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Biomedical subjects

K Nilsson

Publications and source records attributed to K Nilsson.

At least 379 records · Page 21Linked to original sources

Lack of oxygen effect in glutathione-deficient human cells in culture.

The frequency of X-ray-induced DNA breaks was determined in human cell lines which are deficient in glutathione synthetase and have a greatly reduced glutathione content. Hydroxyapatite chromatography was used for the estimation of the DNA breaks in cell cultures, which were derived either from lymphoblasts transformed by infection with EB virus or from fibroblasts. The dose-effect relationship for the induction of breaks when radiation exposure was made in argon, was similar to that found when exposure was made in air. In control cultures with normal glutathione content, the induction of breaks was enhanced when irradiation was made under aerobic, instead of anaerobic, conditions. Treatment of the glutathione-deficient cells with the hypoxic radiosensitizer misonidazole did not enhance the induction of breaks by radiation delivered either in air or in argon. In control cultures, radiation induction of breaks was enhanced by misonidazole under anaerobic but not under aerobic conditions. When the glutathione-deficient cells were pretreated with cysteamine however, irradiation in the absence of oxygen resulted in a decreased frequency of DNA breaks.

Cells, Cultured↗

Isozymes of amino acid naphthylamidase in human haematopoietic cell lines.

The occurrence of isozymes of the proteolytic enzyme amino acid naphthylamidase was investigated in a panel of 44 neoplastic and non-neoplastic haematopoietic cell lines by polyacrylamide gel electrophoresis. Two isozymes (A and C) were common for all lines, whereas different forms of a third isozyme with intermediate electrophoretic mobility (B) appeared in nine lines. Isozyme A seemed to be associated with cell proliferation and was not a marker for malignancy. The appearance of different B isozymes not present in normal peripheral blood lymphocytes, occurred in some Burkitt lymphoma lines and in two non-malignant lines maintained for a long time in culture. In three lines derived from myeloid leukaemia a variant of isozyme B seemed to be a marker for cell origin.

Aminopeptidases↗

p-Toluenesulfonyl chloride as an activating agent of agarose for the preparation of immobilized affinity ligands and proteins.

A number of biomolecules were coupled covalently by nucleophilic displacement to agarose preparations substituted with tosyl groups. In one series of experiments N6-(6-aminohexyl)-adenosine 5'-monophosphate and N6-(6-aminohexyl)adenosine 2',5'-bisphosphate were bound by their terminal amino groups to the polysaccharide support. It could be shown that from a mixture of lactate and 6-phosphogluconate dehydrogenase the immobilized monophosphate showed bio-affinity only for NAD+-dependent lactate dehydrogenase, whereas the immobilized bisphosphate showed affinity only for the NADP+-dependent 6-phosphogluconate dehydrogenase. Furthermore, the immobilized monophosphate (5 mumol/g wet gel) was applied for the single-step purification of lactate dehydrogenase from crude beef heart extract. To demonstrate the immobilization of proteins, soybean trypsin inhibitor (75 mg/g dry support) was immobilized to tosylated agarose, tested as affinity chromatography material and shown to bind 60 mg trypsin/g dry gel. Horseradish peroxidase and horse liver alcohol dehydrogenase were used as model enzymes. Although no optimization had been attempted, the former (approximately 70 mg/g dry support) had a coupling yield of approximately 18% with a specific activity (relative to soluble enzyme) of approximately 10%, whereas approximately 60% of alcohol dehydrogenase was coupled (approximately 100 mg/g dry support) with a specific activity of approximately 25%.

Chromatography, Affinity↗

3H-thymidine uptake in chronic lymphocytic leukaemia cells.

The clinical variability of chronic lymphocytic leukaemia (CLL) is well known. The short and long term prognosis is usually difficult to predict in the individual case. In the present work the proliferative activity in peripheral CLL cells of 38 patients was analysed by 3H-thymidine uptake and a proliferative index (PI = labelling index x white blood cell count/1 x 10(-9)) was calculated. A strong correlation between PI and clinical disease activity was found. Thus 22 out of 23 patients with non-progressive disease had normal values (PI less than 10). 8 out of 8 cases with PI greater than 20 had a clear disease progression in all blood variables. The PI interval 10--20 comprised both patients with progressive and patients with non-progressive disease. Variations in PI correlated well to variations in clinical disease activity in 8 patients examined at intervals during long term treatment. The results indicate that determination of PI might be used as therapy guide since it was normalized during successful treatment.

Absorption↗

Beta 2-microglobulin in chronic lymphocytic leukaemia.

The serum level of beta 2-microglobulin (S-beta 2 m), a cell membrane protein associated with HLA-antigens, was quantitated in a series of 23 consecutive patients with chronic lymphocytic leukaemia (CLL). Markedly elevated values of S-beta 2 m (greater than 4.5 mg/1) were found in 10 patients, while only 3 patients had normal values (less than 3.0 mg/1). High serum values correlated with a large tumour mass, as estimated by Rai's clinical staging and by the total peripheral lymphocyte count. Blood lymphocyte proliferative activity, which has been suggested as reflecting disease activity in CLL, was measured by 3H-thymidine uptake in cells in vitro. The 3H-thymidine uptake was high in 3 patients all of whom were among the 5 patients with the highest S-beta 2m-values. S-beta 2m-determinations seem to be of definite interest in the study of patients with CLL although long term studies will be necessary for evaluation of the practical clinical value.

Aged↗

Measurement and control of quality determining properties of clinical dextrans.

For plasma substitutes a main requirement is that they give plasma volume expansion. For dextran this property has been shown to be molecular weight dependent. The magnitude and duration of the volume effect, and the magnitude and rate of the excretion of dextrans have been carefully studied with regard to the correlation with molecular weight. Other clinically important effects like flow promotion and disaggregation of erythrocytes also have shown correlation with molecular weight. The measurement and control of the molecular weight distribution (MWD) of clinical dextrans thus is an important quality measure. The tolerance limits must be so set that a clinically relevant discriminating effect is obtained. In most of the current official monographs methods give only average figures of the MWDs or of broad fractions of the MWDs. In some cases these figures are not even molecular weight figures but viscosity figures. In the 1960's gel permeation chromatography (GPC) methods were developed for quality control of dextran. These methods are now suggested and considered for some pharmacopoeias, and are already introduced into one, namely the Nordic Pharmacopoeia. With these methods information of the total MWD is obtained. The proportion of dextran in a desirable molecular weight range can be directly seen, and presence of dextran with undesirable molecular weight can be revealed.

Dextrans↗

Mouse red cell receptors on human hematopoietic cell lines.

Spontaneous rosetting with mouse red blood cells (MRBC) seems to be a marker for a subpopulation of B-lymphocytes. We investigated the capacity of different hematopoietic cell lines to form rosettes with MRBC. The cell lines represent different hematopoietic malignancies and the results with these lines were compared with those obtained with non-malignant EBV carrying lymphoblastoid cell lines (LCL). Among tumor cell lines only exceptional lines, 1 myeloma and 2 leukemia lines, showed rosetting capacity with MRBC. Most LCL, however, bound MRBC. These results indicate that only 1 category of established hematopoietic cell line, the LCL, has MRBC receptors and that thus a further subset of B-lymphocyte, the one represented by LCL, has the capacity for rosetting with MRBC. This MRBC rosetting of LCL is, however, not restricted to those lines with S-IgM. Tumor lines of hematopoietic origin seem, however, in general to lack MRBC receptors, even such lines that are derived from malignant lymphomas which express other B-lymphocyte characteristics.

Animals↗

Cell lines with spontaneous secretion of pregnancy-associated alpha 2-globulin.

Pregnancy-associated alpha 2-globulin (PA alpha 2G) was quantitated by radioimmunoassay in culture media from 34 exponentially growing human cell lines. Only 8/34 cell lines produced PA alpha 2G. The highest secretion was found in cell lines of histiocytic lymphoma origin while it was low in some carcinoma-derived lines. The results may support an assumption that PA alpha 2G is a normal cell product of B-lymphoid, monocytic and epithelial cells but may also simply indicate that ectopic PA alpha 2G production is especially common in tumors derived from such cells. The availability of PA alpha 2G-producing cell lines should facilitate studies of the immunoregulatory role of this protein.

Alpha-Globulins↗

Growth of diploid, Epstein-Barr virus-carrying human lymphoblastoid cell lines heterotransplanted into nude mice under immunologically privileged conditions.

Human Epstein-Barr virus-carrying lymphoid cell lines which have been classified on the basis of studies on clonality and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non-neoplastic origin were inoculated intracerebrally into nude mice. All eighteen of them grew, killing the host mice within 7 to 25 days, except for 2 which grew more slowly. At autopsy, the brain of the nudes was found to be invaded by infiltrating lymphomas. Sixteen of these lymphomas, when recultured in vitro, gave rise to cell lines with growth properties and morphology indistinguishable from those of the inoculated LCL. Chromosomal examinations showed that 3/7 cell lines injected, which grew as lymphomas in the brain, were still normal diploid on reexplantation whereas the remaining four had become aneuploid. Four lines derived from intracerebral lymphomas (2 diploid, 1 aneuploid and 1 untested) were inoculated subcutaneously into adult nude mice. None of them grew. When the corresponding four original LCL lines were inoculated subcutaneously into newborn nude mice, they grew rapidly, but failed to do so in newborn normal mice or intracerebrally in adult normal mice. One such line, U-1450, was treated with anti-lymphocyte serum (ALS). Small nodules developed at the site of inoculation. From one nodule a cell line was cultured, 1450 ALSAD. It was morphologically indistinguishable from the line of origin. The lines obtained from nude mice inoculated with polyclonal LCL seem to have a restricted clonal representation, but were not monoclonal, as evidenced by analyses of their pattern of immunoglobulin synthesis.

Aneuploidy↗

Cell surface glycoprotein changes in Epstein-Barr virus-positive and -negative human hematopoietic cell lines.

It has previously been shown that differential fucose labelling of many normal and homologous tumor cells, followed by proteolytic release and degradation, yields glycopeptides which upon gel filtration shown an increase in fast-eluting glycopeptides for the tumor cells. This technique has now been applied to cell-surface glycoproteins of different human hematopoietic cell lines. These lines included Epstein-Barr virus (EBV)-carrying lymphoblastoid cell lines of presumed non-neoplastic origin, and malignant EBV-genome-positive Burkitt lymphoma and EBV-negative non-Burkitt lymphoma, leukemia and myeloma lines. As compared with normal peripheral lymphocytes, both the lymphoblastoid type of cell lines and the different types of lines of proven malignant ancestry contained the fast-eluting glycopeptides on their cell surface with very few exceptions. It is therefore concluded that (I) malignant conversion of human lymphoid cell in vivo is commonly, but not obligatorily, associated with a specific change in the composition of the fucosyl glycopeptides, and (2) EBV infection of B lymphocytes does not lead only to the well-documented immortalization in vitro but also, as a rule, to the same type of alteration in fucosyl glycopeptides as was demonstrated for the neoplastic cell lines. It proved possible to distinguish several categories of hematopoietic cell lines due to the effect that pretreatment of the glycopeptides with neuraminidase or mild acid exerted on their subsequent chromatographic behavior.

Burkitt Lymphoma↗

K562--a human erythroleukemic cell line.

We have studied the surface membrane properties of the human leukemic cell line K562 which previously has been reported to represent an early stage of granulocyte maturation. The surface glycoprotein pattern of the K562 cells obtained after galactose oxidase-NaB[3H]4 labelling and slab gel electrophoresis shows striking similarities with that of normal erythrocytes but is completely different from the patterns of normal and malignant cells of various stages of the myeloblast to granulocyte differentiation. Moreover, the K562 cell expressed the major red cell sialoglycoprotein, glycophorin, on its surface as shown by immunofluorescence and by immunoprecipitation from labelled membrane preparations. As glycophorin is exclusively found on erythroid cells in human bone marrow we conclude that the K562 is a human erythroleukemic line.

Antigens, Surface↗

Specific changes in the surface glycoprotein pattern of human promyelocytic leukemic cell line HL-60 during morphologic and functional differentiation.

The human promyelocytic leukemia cell line HL-60 can be induced to undergo morphological and functional differentiation in vitro by various low molecular weight compounds. The cellular morphology changes from blastoid appearance to that of granulocytes and the cells acquire the ability to phagocytize. We here report that the surface glycoproteins specifically change during this differentiation, as shown by the neuraminidase/galactose oxidase/NaB3H4 surface-labeling technique followed by polyacrylamide slab gel electrophoresis. The most prominent change is the loss of the major glycoprotein band typical for the blast cells which has an apparent molecular weight of 160,000 and the appearance of a major surface glycoprotein band with an apparent molecular weight of 130,000. Expression of the 130,000 molecular weight band correlates with the appearance of phagocytic and chemotactic activities of the cells. It has the same molecular weight as the major surface glycoprotein of freshly isolated human blood granulocytes.

Cell Differentiation↗

Small endotracheal tubes: ventilator and intratracheal pressures during controlled ventilation.

The use of small endotracheal tubes reduces the trauma of intubation. Ventilator and tracheal pressures were measured during controlled ventilation with various tube dimensions and ventilation volumes. Ventilation with large volumes using small tracheal tubes results in high ventilator pressures. However, tracheal pressures are only marginally greater than those obtained with larger tubes. Small endotracheal tubes and high ventilation volumes result in a positive tracheal pressure at the end of expiration. The measured end-expiratory pressures are within the limits which might be used therapeutically (in PEEP). The force required to reshape endotracheal tubes of varvious dimensions to an "anatomical" shape was related to the tube dimensions; the beneficial effects of performed, "anatomically shaped" endotracheal tubes can be achieved by using small tubes of standard design.

Adult↗

Continuous wearing of Duragel contact lenses by Swedish air force pilots.

This is a report of the application of contact lenses for prolonged wear by military pilots. The safety and effectiveness of wearing these non-HEMA hydrophilic lenses in a highly demanding visual environment is described in the case of an individual jet-fighter pilot who has worn these lenses continuously for 3 years without any complications.

Adult↗

Interferon therapy in multiple myeloma.

A woman with multiple myeloma relapsed after 6 years of satisfactory tumor control with melphalan therapy. When progression then occurred, she was given exogenous human leukocyte interferon, 3 x 10(6) reference units twice daily i.m., as the sole therapy. Side-effects of the interferon therapy consisted of fever reactions and thrombocytopenia. One month after the initiation of interferon therapy there was 1) improvement of general health with less pain and tiredness, 2) reduction of the M-component, IgG-lambda, in the serum, and 3) a reduced plasma cell concentration in the bone marrow. After 5 months of interferon therapy tumor progression occurred despite continuous interferon treatment. At the same time, the tumor cells were less sensitive to interferon in in vitro tests than prior to interferon therapy. It is suggested that interferon therapy should be given as initial treatment to a few patients with multiple myeloma in a phase I trial.

Aged↗

Gamma globulins of CSF and serum in multiple sclerosis: isoelectric focusing on polyacrylamide gel and agar gel electrophoresis.

Cerebrospinal fluid (CSF) and serum from 139 patients with MS were analyzed with electrophoresis on agar gel (AGE) and isoelectric focusing (IEF) on polyacrylamide gel. In both methods, 82 percent of the patients had abnormal patterns of oligoclonal IgG bands in the gamma globulin and alkaline regions. With IEF, 10 percent of the serum samples contained faint bands corresponding to the bands in CSF. Most of the bands were found in the cathodal part of the alkaline IEF region, but there was no correlation with clinical characteristics. Each patient seems to have a special band pattern which does not change throughout the disease. The gamma-trace protein was seen in 77 percent of the patients on IEF and in 29 percent on AGE. On IEF it appeared at two positions, at pH 8.0 and 9.3, but about 10 other bands were seen in the "normal" alkaline CSF region, making the band pattern of IEF more difficult to interpret than that of AGE. This limits the routine clinical value of IEF, even if the high resolution capacity of this method is useful in research.

Adolescent↗