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L Olsson

Publications and source records attributed to L Olsson.

At least 109 records · Page 6Linked to original sources
PubMed1985

On the natural biology of the malignant cells in Hodgkin's disease.

The biological attributes and cellular origin of the malignant cells in Hodgkin's disease have been subject to numerous investigations both on fresh biopsy material and from long-term in vitro cultures of cells derived from Hodgkin's disease lesions. Studies on fresh biopsy material have led to suggestions that Hodgkin's cells are derived from T-lymphocytes, B-lymphocytes, or monocytes/macrophages. However, all these studies are hampered by the low amounts of Reed-Sternberg cells in the neoplastic lesions as well as some technical difficulties. It has consequently been desirable to establish long-term cell cultures of the malignant Hodgkin's cells, and the technical problems as well as the experimental outcome of these studies are reviewed. Among the technical, the potential and limitations in the use of monoclonal antibodies are described in particular. A number of cell lines from Hodgkin's disease lesions have been described, but a critical appraisal of these studies reveal that most of the published cell lines can be dismissed as being non-representative for Hodgkin's and Reed-Sternberg cells; most of the cell lines are thus EBV-transformed lymphocytes and in some cases even non-human cell lines. Two cell lines (L428 and SU/RH-HD-1), however, seem to be derived from the malignant cell population in Hodgkin's disease. The phenotypic analyses of these lines--and in particular the SU/RH-HD-1 line--strongly indicate that these cells have monocyte/macrophage attributes, and it is concluded that Hodgkin's disease is a neoplasm of cells in the monocyte/macrophage lineage.

Antibodies, Monoclonal↗
PubMed1985

Treatment of human cell lines with 5-azacytidine may result in profound alterations in clonogenicity and growth rate.

Liquid medium cultures of three human cell lines (B-lymphoma, myeloma, and squamous lung carcinoma) with population-doubling times (PDT) and cloning efficiencies (CE) in the range of 32-43 h and 0.01-5.6%, respectively, were exposed to 5-azacytidine (5-azaC) for 3 d. The doses used (1-3 microM) were found to be nontoxic as measured by cell growth in liquid and semisolid agar medium and to be nonmutagenic as measured by the rate of generation of ouabain- and 6-thioguanine-resistant cell variants. After 5-azaC treatment, cell samples were subsequently harvested every day and assayed for their CE in semisolid agar medium. For each cell line, 30 to 42 individual clones were harvested at the day of maximal CE and expanded in liquid culture medium. PDT and CE were determined for each subclone about every 6 wk for 12 mo. The majority of the subclones had unaltered PDT and CE compared to the original lines. However, several clones had profoundly changed proliferative activity with PDT on approximately 12-14 h and/or CE 5 to greater than 50%. Some of the clones with altered growth properties reverted to PDT and/or CE values of untreated clones. However, a few clones of each line had stable alterations with PDT on 12-14 h and CE 5 to greater than 50%; these clones were all significantly hypomethylated. It is concluded that the human gene repertoire does contain genes that appropriately activated can result in growth properties with very short PDT and high CE (and comparable to animal cell lines), and that this activation may be obtained by 5-azaC treatment. It is conceivable that the procedure here described to alter growth properties of human cell lines may be applied to experimental situations, where alterations of cell growth properties are desired.

Azacitidine↗
PubMed1985

Carnitine and left ventricular function in haemodialysis patients.

Left ventricular function was non-invasively studied in 28 randomly selected haemodialysis patients before and after administration of L-carnitine, 2 g i.v. three times per week or saline in a double blind designed study over a six-week period. Cardiac function variables showed no relationship to muscle (vastus lateralis) and plasma carnitine concentrations. No apparent deficiency in muscle carnitine was found, whereas total plasma carnitine was lower in female patients than in female controls, p less than 0.002. The echocardiographic left ventricular end-diastolic diameter was initially increased in about one third and the ejection fraction was depressed in about one fifth of the patients. An increased A:H ratio was found in 15%. Systolic time intervals were deranged in 30% of the patients. After carnitine administration, marked increases of muscle and plasma carnitine levels were found, p less than 0.01, but no effects were recorded in any of the cardiac tests. Muscle carnitine increased from 14.6 mmol/kg dry weight to a median of 23.7 mmol/kg. We found no support for the hypothesis that carnitine depletion is responsible for cardiac dysfunction in haemodialysis patients.

Adult↗
PubMed1985

Phenotypic attributes of the malignant cell population in Hodgkin's disease indicate a monocyte/macrophage origin.

The cellular origin of the malignant cells in Hodgkin's disease (HD) has been discussed for several decades. Previous investigations on fresh biopsy material and cultured cells from lesions of Hodgkin's disease have led to various suggestions such as a T lymphocyte, B lymphocyte or monocyte/macrophage origin of HD cells. However, all these studies have been hampered by uncertainty in the identification of the truly malignant cells. It has therefore been desirable to establish in vitro lines of the malignant cell population in HD. A number of cell lines from HD lesions has been described, but most of these studies can, upon a critical appraisal, be dismissed as not being representative for Hodgkin's and Reed-Sternberg cells. We report on the phenotypes of established cell lines of Hodgkin's cells and conclude that it is most likely that the malignant Hodgkin's cells are derived from cells of the monocyte/macrophage lineage.

Cell Line↗
PubMed1984

Intratumoral phenotypic diversity of cloned human lung tumor cell lines and consequences for analyses with monoclonal antibodies.

Cloned cell lines and a number of subclones from these lines were established in vitro from biopsies of small cell lung carcinomas and squamous cell lung carcinomas. The cloned cultures, including the cloned subclones, were analyzed in respect to morphology, karyotype, growth rates, clonogenicity in semisolid agar medium, and tumorigenicity in nude mice. A remarkable biologic diversity was found in respect to most of these biologic features. In addition, four murine monoclonal antibodies with high specificity for lung tumor cells were generated. Their reactivity pattern to clonogenic cells was for some clones different as compared to the nonclonogenic cells. Subclones of tumor cells not binding the antibody were identified for each monoclonal antibody. It is concluded that intratumoral phenotypic diversity may have a severe negative impact on the use of monoclonal antibodies in cancer diagnosis/therapy. The work also indicates that a mixture of antibodies may be more useful in tumor diagnosis than individual antibodies and perhaps even therapy, particularly if they bind to the clonogenic part of a cell population.

Antibodies, Monoclonal↗
PubMed1984

Antibody producing human-human hybridomas. II. Derivation and characterization of an antibody specific for human leukemia cells.

Human-human hybridoma technology was used to immortalize human B lymphocytes from patients with acute myeloid leukemia (AML) to study the antigenic repertoire of the humoral immune response against the patients' own leukemia cells and against leukemic cells from other patients. Nine fusions were done with lymphocytes from seven AML patients, and all with the human RH-L4 B lymphoma line as malignant fusion partner. A total of 305 Ig-producing hybrids were obtained. 26 reacted with cell surface components on AML cells, but 21 were found not to be specific for leukemia cells, when screened for reactivity against a panel of normal and malignant cells of both human and murine origin. Five hybridomas secreted Ig with high specificity for human leukemia cells, but only one hybridoma culture, aml-18, was stable in respect to Ig-production and growth upon repeated clonings and expansion in liquid cultures. A method was developed to grow human hybridomas as ascites tumors in nude mice, but the ascites fluid did not contain increased amount of antibody. The reactivity of the aml-18 antibody (gamma, kappa) was analyzed against samples of mononuclear cells from peripheral blood of 63 patients with leukemia and with cytologically verified leukemia cells in the blood. 22 of 54 AML samples reacted with aml-18. The reactivity pattern was not correlated to any categories of the French-American-British (FAB) classification; two of four ALL were positive. Moreover, a pronounced intratumoral antigenic heterogeneity in regard to aml-18 reactivity was seen and indicates a high degree of diversity in the immunological phenotype within individual AML cell populations. The study demonstrates that some patients with AML generate an immune response against their autologous malignant cells, and that the antigenic determinant in the case of aml-18 is also expressed specifically on leukemic cells from other patients.

Antibodies, Monoclonal↗
PubMed1984

Human monoclonal antibodies: methods of production and some aspects of their application in oncology.

The currently available methods for the production of human monoclonal antibodies (Mabs) are: mouse-human hybrids, human-human hybrids, EBV transformation, and fusion of EBV-transformed specific B-lymphocytes with a malignant cell line. Each method has its advantages and drawbacks, but they are all inferior to an optimal functioning mouse hybridoma system. A significant obstacle is the lack of a reproducible method to obtain high amounts of antigen-specific B-lymphocytes. However, it seems that newly developed in vitro antigen-priming methods may be a significant aid to the solution of this problem. Human Mabs have already been obtained against some types of human cancer, and the reactivity pattern has provided some biological information that seems not to be obtainable with non-human Mabs. It furthermore seems that the technology for production of human Mabs now has progressed to the stage where it permits a realistic hope that they soon can be applied in the diagnosis and treatment of human cancer.

Animals↗
PubMed1984

Induction of the metastatic phenotype in a mouse tumor model by 5-azacytidine, and characterization of an antigen associated with metastatic activity.

The murine Lewis lung carcinoma is a long-term grafted tumor that, after subcutaneous inoculation, forms metastases to the lungs. Forty-two cell lines were established from a primary tumor site and 40 were established from lung metastatic foci. Cloned sublines were established from the original 82 lines, and 2 sublines among 405 were found to be tumorigenic but not metastatic (T+/M-), whereas the remaining 403 sublines were both tumorigenic and metastatic (T+/M+). The T+/M- phenotype was shown to be stable for greater than 2 yr. However, treatment of the T+/M- cell lines for 3 days with 3 microM 5-azacytidine resulted in reexpression of the metastatic phenotype in otherwise stable T+/M- lines. Also, 5-azacytidine treatment could result in loss of the metastatic phenotype in lines that had been stable T+/M+. The changes in tumorigenic and metastatic phenotypes were not associated with altered immunogenicity of the cells. Monoclonal antibodies were generated against T+/M+ cells, and one antibody ( M36D3 ) was found to bind only to T+/M+ cells. Reactivity of the antibody was found to co-vary with expression of the metastatic phenotype. The antigen recognized by M36D3 antibody thus seems to be associated with metastatic capability. The antigen was found by two-dimensional gel electrophoretic analysis to be a cellular protein of Mr approximately equal to 45,000 and pI approximately equal to 6.7.

Animals↗
PubMed1984

Establishment and characterization of a cloned giant cell line from a patient with Hodgkin's disease.

The phenotypic characteristics of a cloned giant cell line, SU/RH-HD-1, established from the spleen of a patient with Hodgkin's disease were studied. The cells grew slowly, adhered to the culture vessel surface, and had an elongated, irregular shape. After trypsinization, they became spherical and measured 30-100 micron in diameter. Although most cells were mononuclear, binucleated and multinucleated cells could be identified in expanded cultures. The cells phagocytized latex and ink particles and were nonspecific esterase-positive, but they did not secrete lysozyme. They were Epstein-Barr nuclear antigen-negative, and their culture fluid supernatants were devoid of reverse transcriptase activity. Electron microscopy revealed cells with a pronounced smooth endoplasmic reticulum, free ribosomes, some filaments, and mitochondria. Many 0.5- to 1.0-micron invaginations (pits) were seen along the cell membrane. Nucleoli were enlarged and prominent in the very heterochromatic nuclei. The SU/RH-HD-1 cells had 10- to 100-micron-long pseudopodia that were sometimes forked or branching, as well as multiple stress fibers. Electron microscopic appearance was suggestive of that of macrophages. This interpretation of the results was substantiated by monoclonal antibody studies, which revealed that the cells express antigenic determinants distinctive for cells of the monocyte-macrophage lineage and by functional studies demonstrating that the cells are capable of specific antigen presentation to immune T-cells. The SU/RH-HD-1 cells were aneuploid and could be cloned, first in liquid culture by limiting dilution and later in semisolid medium. It was likely that the SU/RH-HD-1 cells were derived from the neoplastic giant cell population in Hodgkin's disease and that they originated from cells of the mononuclear phagocyte-reticulum cell lineage.

Animals↗
PubMed1984

A human monoclonal antibody specific for tetanus toxoid.

Successful hybridization has been obtained between PWM stimulated peripheral blood lymphocytes from tetanus toxoid immunized donors and the human B lymphoma line RH-L-4. Among the hybrids selected after cloning, the average in vitro activity against tetanus toxoid was 1-5 micrograms/10(6) cells/24 hours. The specific activity of one of them was further tested in vitro (RIA) and in vivo (mouse protection test) and compared favourably with a human polyclonal antitetanus globulin.

Animals↗
PubMed1984

Comparison between fluorescein angiography and fluorescein microscopy.

Fluorescein angiography (FA), which implies that the tissue is reproduced in natural size, and fluorescence microscopy was compared in anesthetized normovolemic and hypovolemic rats in order to define the microscopic background to the fluorescence pattern obtained by FA. It was found that the fluorescence detected by FA by the use of sodium fluorescein as an indicator substance was emitted from the interstitial and intracellular compartments, including the intranuclear. Microscopy showed that sodium fluorescein was located extravascularly in the small intestine within 4 seconds after an intravenous injection. There was a 4 second interval between corresponding microscopic and macroscopic fluorescence pattern.

Angiography↗
PubMed1983

Antibody producing human-human hybridomas. I. Technical aspects.

Technical aspects of generation of antibody-secreting human-human hybridomas are evaluated as based on 100 human-human fusions with a human B-lymphoma cell line (RH-L4) or the SKO-007 myeloma cell line as malignant fusion partners, and compared with similar fusion conditions in the mouse hybridoma system. The yield of hybrids was significantly lower when normal peripheral blood lymphocytes were used as fusion partners as compared with spleen lymphocytes, but could be substantially improved by increasing the amount of mitotic active B-lymphocytes by mitogen stimulation of the lymphocytes, preferably in HAT medium, prior to fusion. Furthermore, human hybrids grew slower and had a higher degree of chromosomal instability than usually observed in the mouse hybridoma system. Thus, out of 72 fusions, only 3 stable hybrids with antibody production against a predefined antigen were established. The importance of improved sources of human B-lymphocytes for human-human hybridoma production is discussed and methods of obtaining such improvement suggested.

Animals↗
PubMed1983

Cloning of human hybridoma, myeloma and lymphoma cell lines using enriched human monocytes as feeder layer.

Human monocytes were prepared from peripheral blood by buoyant density centrifugation and subsequent absorption-elution on a column of gelatin beads. The eluted fraction containing 60-80% monocytes was used as feeder layer in cloning of the human lymphoma line RH-L4, the human myeloma line SKO-007, and a human hybridoma cell derived from the latter line. Cloning efficiencies were high in both liquid and semisolid media with all 3 cell lines tested. Feeder monocytes could also be successfully used after having been stored in liquid nitrogen.

Animals↗
PubMed1983

Phenotypic diversity in leukemia cell populations.

Acute leukemia comprises a large group of different diseases that can be identified by morphology in combination with immunological markers. Such studies suggest that phenotypic heterogeneity may be expressed in individual leukemia cell populations. This was verified in the murine AKR leukemia that was found to be composed of four antigenically different subtypes of leukemia cells, and it was shown that this feature has a severe negative impact on the use of leukemia cell specific monoclonal antibodies (Mabs) as therapeutical reagents. Twenty-four human T-lymphoblastic leukemias were analyzed with Mabs against HLA class I, HLA class II, and T-lymphocyte differentiation antigens, and 21 were found to be intratumoral heterogeneous with respect to these antigens. Mabs with high specificity were generated against AML cells and subsequently used to analyze more than 50 AML samples from different patients. The reactivity pattern of the Mabs differed significantly among the various AML samples. Further, a pronounced intratumoral antigenic heterogeneity (IAH) was found in most AML samples with regard to reactivity of the Mabs against AML and expression of major histocompatibility antigens. The negative impact of IAH on the use of Mabs in clinical oncology is described. It is argued that IAH exemplifies the phenotypic diversity of malignant neoplasms which is also suggested to be a basic and necessary feature of malignant cell populations. Mabs against subsets of malignant cell populations may have a profound effect on cancerous cell populations, and it is therefore of crucial importance that such subsets are identified and characterized. It is conceivable that this may result in generation of Mabs with potentially high value in cancer diagnosis and therapy, particularly in combination with drugs that induce differentiation in the malignant cell mass.

Animals↗