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Biomedical subjects

R Andreesen

Publications and source records attributed to R Andreesen.

At least 145 records · Page 8Linked to original sources
PubMed1984

Expression of transferrin receptors and intracellular ferritin during terminal differentiation of human monocytes.

Human blood monocytes when cultured on hydrophobic Teflon membranes differentiate into mature macrophages. The expression of transferrin receptors was monitored by monoclonal antibody (OKT9) binding as detected by immunoperoxidase staining. Whereas monocytes were negative, an increasing percentage of macrophages, starting from day 2 in culture, labelled with the antitransferrin receptor antibody as these cells undergo differentiation. After completion of maturation more than 90% of macrophages expressed transferrin receptors. While 90-95% of macrophages from broncho-alveolar lavage fluids labelled with the OKT9 antibody, only a minor portion of macrophages obtained from peritoneal and pleural cavities did so. In parallel, intracellular ferritin in cells of the monocyte-macrophage lineage increased from 10 ng/10(6) cells to 350-1,500 ng/10(6) cells during maturation in vitro. Alveolar macrophages proved to have the highest ferritin content which ranged from 355-8,400 ng/10(6). The results may indicate that iron uptake and storage is a function of cells at late stages of macrophage maturation and that the occurrence of surface receptors for transferrin can be regarded as differentiation dependent marker.

Antibodies, Monoclonal↗
PubMed1984

Tumor cytotoxicity of human macrophages after incubation with synthetic analogues of 2-lysophosphatidylcholine.

Human alveolar macrophages as well as macrophages derived from Teflon culture of blood-borne monocytes were incubated with synthetic analogues of 2-lysophosphatidylcholine and then tested for their cytotoxic capacity against an allogeneic lymphoma cell line. Metabolic, rather stable analogues enhanced macrophage cytotoxicity significantly. This phenomenon was shown both in a growth-inhibition assay as well as in the 51Cr release assay. Macrophage activation was dose- and time-dependent and was potentiated at temperatures above 37 degrees C. Incubation of the macrophages with the active compounds induced characteristic changes in cell morphology as revealed by scanning electron microscopy.

Antineoplastic Agents↗
PubMed1984

A Hodgkin cell-specific antigen is expressed on a subset of auto- and alloactivated T (helper) lymphoblasts.

A Hodgkin cell-specific antigen detected by the monoclonal antibody Ki-1 was found on T helper lymphocytes after activation by autologous and allogeneic stimulator cells. About 50% of lymphoblasts generated by auto- and alloactivation reacted with the antibody. In contrast, only less than 6% of lymphoblasts stimulated with Con-A, phytohemagglutinin (PHA), or protein A, and none of lymphoblasts activated by oxidative mitogenesis, expressed this antigen. Among several permanent cell lines tested, the K562, MOLT-4, HL-60, and EBV transformed B lymphoblastoid cells reacted with the Ki-1 antibody. The results may indicate possible relationships between the autoreactive subset of T lymphocytes and the pathogenesis of Hodgkin's disease.

Antibodies, Monoclonal↗
PubMed1983

Primary cultures of human blood-born macrophages grown on hydrophobic teflon membranes.

Human blood-born monocytes have been cultivated on the hydrophobic side of Teflon foils (fluorinated ethylene propylene copolymer) using human pooled AB-serum as essential growth factor. At any stage of culture these in vitro maturing macrophages can easily be detached from the Teflon membrane and subjected to further experimentation. Once established, primary macrophage cultures can be maintained in medium containing 10% FCS for up to 3 months. Lysozyme secretion increased more than 10-fold during the sequential process of monocyte transformation into macrophages and correlates with cell number and stage of maturation. The ability to inhibit growth of human permanent tumor cell lines also developed during macrophage maturation. Studies on the cells of 22 healthy donors revealed a reproducible activity of mature macrophages against K562 and MOLT4 tumor cells. Our system will facilitate investigations on various aspects of human macrophage differentiation and function.

Blood Cells↗
PubMed1983

Enhancement of spontaneous and lymphokine activated human macrophage cytotoxicity by hyperthermia.

Human macrophages grown on hydrophobic teflon membranes from blood-born monocytes were incubated at hyperthermic temperatures for various time periods and then tested for their ability to inhibit the growth of an allogeneic lymphoma cell line (U 937). Incubation at 40.5 degrees C greatly enhanced macrophage cytotoxicity. This effect of hyperthermia developed slowly with an optimal incubation period of 48 h. In addition, lymphokine activation of macrophages for cytotoxicity appeared to be more effective at elevated temperatures.

Cell Line↗
PubMed1983

Cell-destructive activity in the serum of a tumor patient after infusion of alkyl lysophospholipid.

Sera collected from 1 tumor patient after a 12-hour infusion of 30-50 mg alkyl lysophospholipids (ALP)/kg induced a progressive destruction of human leukemia cells (HL60) in vitro. This cytotoxic serum activity correlated with the dose of ALP administered and was inhibited by the addition of a metabolizable lysophospholipid analogue. Human bone marrow cells and concanavalin A-stimulated lymphoblasts were affected to a much lesser degree, whereas cells of the erythroleukemia line K562 appeared to be relatively resistant. When cells were cultured in postinfusion sera, the cytotoxicity of ALP in vitro was enhanced as much as fifteenfold when compared with the cytotoxicity of ALP when the cells were cultured in normal sera. No change in either relative or absolute distribution of phospholipids in postinfusion sera could be detected.

Adult↗
PubMed1983

Cytotoxic effector cell function at different stages of human monocyte-macrophage maturation.

Human blood-borne monocytes were cultured for up to 22 days on disposable Teflon foils. Within 8 days, these monocytes developed into mature macrophages. At various stages of differentiation, the cells were recovered from the hydrophobic membrane and were assayed for typical monocyte-macrophage enzymes and morphology, binding of monoclonal antibodies (OKM1, OKla1), Fc and transferrin receptors, phagocytic activity, lysozyme production, and ability to inhibit the growth of an allogeneic tumor target cell line (U937). A significant antitumor activity of mature macrophages was found, which developed along with the differentiation of the monocyte precursor cells. In addition, cytotoxic effector macrophages could be activated by lymphokine-rich medium and synthetic alkyl-lysophospholipids. After density gradient separation, light cells (less than 1.05 and less than 1.06 g/ml) showed enhanced cytotoxicity, whereas cells from the dense fraction (greater than 1.06 g/ml) with low base-line activity could be best activated for cytotoxicity by lymphokines. If monocyte-macrophages are involved in a natural surveillance mechanism, our results may indicate the importance of unimpaired macrophage maturation to generate effective host defense against tumor development.

Cell Adhesion↗
PubMed1983

Temperature dependence of leukemic cell destruction by alkyl-lysophospholipids (NSC 324368).

Alkyl-analogs (ALP) of 2-lysophosphatidylcholine induce a progressive destruction of neoplastic cells by interfering with the continuous turnover of membrane phospholipids. Using leukemic blast cells from patients with acute forms of leukemia the effect of temperature was evaluated. It was found that temperature strongly influences the cytotoxic activity of ALP. High temperatures potentiate whereas a slight decrease in temperature reduces leukemic cell destruction by ALP. At temperatures below 30 degrees C even high doses of ALP will not destroy these tumor cells. Furthermore, cell destruction initiated at 37 degrees C can be abolished by lowering the incubation temperature to 25 degrees C. These biological data have been confirmed by biochemical studies, showing a temperature dependence of ALP adsorption not accompanied by a corresponding increase of alkyl-cleavage enzyme activity. The rate of membrane phospholipid turnover seems to be essential for temperature dependent ALP induced cell destruction.

Acute Disease↗
PubMed1982

Cytotoxic activity in the serum of a patient with metastasizing nephroblastoma given intravenous infusions of alkyl-lysophospholipids in a phase I study.

In a phase I study a cytotoxic activity in the serum of a tumor patient given infusions of synthetic alkyl-lysophospholipid has been demonstrated. Serum samples collected after ALP infusions inhibited 3H-thymidine incorporation by human leukemic cells to an extent that correlated to the dose of ALP administered. Serum taken after the highest dose of ALP given (50 mg/kg body weight) led to complete cell destruction after 72 h in vitro. Whereas cells from the HL60 line were very sensitive to the serum cytotoxicity, K562 cells were much less affected. Cytotoxic activity was found to be clear from the circulation in a biphasic manner; more than 50% disappeared within 6-8 h but 20-30% was still present after 4 days.

Adult↗
PubMed1980

Alkyl-lysophospholipid induced suppression of human lymphocyte response to mitogens and selective killing of lymphoblasts.

Alkyl-analogs of 2-lysophosphatidylcholine have been found to inhibit the response of human peripheral blood lymphocytes to mitogens and allogeneic cells. Furthermore, these compounds kill selectively transformed lymphocytes in vitro while resting lymphocytes are not affected in their viability. The increased incorporation of fatty acids into cellular phospholipids during lymphocyte stimulation has been shown to be inhibited by these alkyl-lysophospholipids. Both resting and transformed lymphocytes could be shown to have an 1-0-alkyl-cleavage enzyme. Thus, selective cytotoxicity for lymphoblasts is not due to principal differences in the metabolism of alkyl-lysophospholipids as we have demonstrated to be the case between normal and leukemic cells, but is most likely due to the interference of these substances with the enhanced turnover of cellular phospholipids in stimulated lymphocytes.

Concanavalin A↗
PubMed1980

Destruction of human solid tumors by alkyl lysophospholipids.

Alkyl lysophospholipids (ALP) are synthetic analogs of the naturally occurring 2-lysophosphatidylcholine. The effect of ALP on the proliferation of 22 different gynecologic malignant tumors in humans was studied in vitro. ALP caused progressive death of tumor cells over 24-96 hours. In addition, tumor specimens from the tested human tumors were xenotransplanted into NMRI nude mice. ALP induced a highly significant retardation of the in vivo growing human tumors. Neither oral nor iv administration of these compounds caused any recognizable side effects.

Adenocarcinoma↗
PubMed1979

Selective sensitivity of chronic myelogenous leukemia cell populations to alkyl-lysophospholipids.

In order to evaluate the specificity of alkyl-lysophospholipid-induced cell destruction, peripheral blood leukocytes from chronic myelogenous leukemia (CML) patients in chronic phase of the disease as well as in blastic crisis have been separated by density centrifugation. These subpopulations, enriched for the different maturation stages, were tested for their sensitivity to alkyl-lysophospholipids. It is shown that myelocytes in chronic phase CML are resistant, but blast cells from both clinical stages as well as maturational defective myelocytes from blastic crisis CML are highly sensitive to these antimetabolites. In contrast to chronic phase CML myelocytes, these sensitive cells show a high lysophospholipid adsorption rate and lack an O-alkyl-cleavage enzyme.

Chronic Disease↗
PubMed1979

Disturbance of phospholipid metabolism during the selective destruction of tumor cells induced by alkyl-lysophospholipids.

Alkyl-lysophospholipids inhibit the growth of Meth A sarcoma cells in vitro. In contrast, murine bone marrow macrophages are not sensitive to the destructive effect of these substances. Since alkyl-lysophospholipids are antimetabolites in the synthesis of 3-sn-phosphatidylcholine, tumor cell destruction can be correlated with the disturbance of this metabolism. A decreased synthesis of 3-sn-phosphatidylcholine is accompanied by an increased degradation of cellular 3-sn-phosphatidylcholine in the presence of alkyl-lysophospholipids. As a consequence, endogeneously formed lysophospholipid accumulates, although the lysophospholipase is found to be stimulated. This accumulation of endogeneous lysophospholipids might be due to the fact that a high percentage of these compounds contain an alkyl bond which cannot be split by a lysophospholipase. On the other hand, the reacylation of the formed lysophospholipids is partially blocked as the lysophosphatidylcholine acyltransferase is inhibited by the added alkyllysophospholipids. An accumulation of potentially cytotoxic lysophospholipids in tumor cells might be an additional factor in the tumor cell destruction by alkyl-lysophospholipids.

Animals↗
PubMed1975

[Meniscopathy as occupational disease (author's transl)].

Meniscopathy develops through internal causes alone without any external influence. Work such as that of a miner underground, which is associated with particular strain on the knee joint may aggravate this disorder. If such work has been carried out for at least 3 years, an occupational disease is to be assumed. If the complaint only makes its appearance 5 years after ending injurious work, the causal connection must be assessed critically, taking into account age, duration of work and the results of microscopic investigations.

Adolescent↗