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Biomedical subjects

R Keller

Publications and source records attributed to R Keller.

At least 307 records · Page 17Linked to original sources
PubMed1983

Discrimination between macrophage-and NK-type tumoricidal activities via anti-asialo GM1 antibody.

The usefulness of asialo GM1, a glycolipid surface marker, to define the effector cell types involved in tumor resistance in vitro and in vivo was assessed. Pretreatment of rat effector cells with anti-asialo GM1 antibody plus complement in vitro either abrogated or markedly diminished NK activity; in contrast, macrophage-type cytocidal activity was not diminished by such pretreatment. Similarly, systemic inoculation of anti-asialo GM1 antibody selectively eliminated NK activity, leaving macrophage-type tumoricidal reactivity intact. Finally, such pretreatment did not diminish host resistance in an in vivo tumor model in which the available evidence suggests a critical role for macrophages. The asialo GM1 marker may thus be useful in delimitating the tumoricidal capacity of cells exhibiting NK activity from that mediated by other cell types.

Animals↗
PubMed1982

Mononuclear phagocytes in the control of primary and secondary tumor growth.

In a variety of defined experimental host/tumor situations there is now considerable evidence that mononuclear phagocytes are critically involved in the control of tumor cell nidation and their establishment as primary tumors. The factors which determine secondary tumor cell spread and the establishment of metastases are clearly complex and make it highly unlikely that tumor cell dissemination is under the control of a single host defense mechanism. Nonetheless, findings in various experimental models suggest a critical role for mononuclear phagocytes in the surveillance of tumor cell dissemination.

Animals↗
PubMed1982

Divergency between incidence of microscopic and macroscopic metastases.

In a rat fibrosarcoma model (D-12), the incidence of macroscopic metastases was generally low but critically dependent on the site of the primary tumor implant; surgical removal of the primary tumor either induced or markedly enhanced the outgrowth of macroscopic metastases (Keller 1981). The present histological and biological findings indicate that dissemination of neoplastic cells and colonization of draining lymph nodes is a spontaneous, early occurring and continuing process. The incidence of micrometastases within lymph nodes by far exceeded the incidence of macroscopically evident metastases. Other evidence suggests that the growth characteristics of D-12 tumor cells derived from metastases are not measurably different from D-12 cells inducing primary tumor growth.

Animals↗
PubMed1982

Natural cytotoxicity of murine cytomegalovirus-infected cells mediated by mouse lymphoid cells: role of interferon in the endogenous natural cytotoxicity reaction.

Lymphoid cells from unstimulated normal C57BL/6J mice were shown to lyse murine cytomegalovirus (MCMV)-infected syngeneic mouse embryo fibroblasts but not uninfected mouse embryo fibroblasts. This cytotoxicity by mouse effector cells was not restricted to MCMV-infected syngeneic cells since MCMV-infected xenogeneic rat heart fibroblasts were also lysed. Characterization of the effector cells mediating this cytotoxicity against MCMV-infected cells indicated that the effector cells are similar to described natural killer (NK) cells mediating lysis of tumor cells and virus-infected cells. Because of the described augmentation of NK activity by interferon, we examined the role of interferon in the NK reaction. Although low levels of virus-induced interferon were detectable in supernatants of MCMV-infected mouse embryo fibroblasts, no interferon was detectable in supernatants of MCMV-infected rat heart fibroblasts, a target significantly more sensitive to NK cytolysis than infected mouse embryo fibroblasts. We were able to augment the NK reaction against MCMV-infected cells by in vitro treatments with interferon. However, the amounts of interferon required for augmentation were significantly greater than the amounts generated by infected target cells. In vitro interferon-stimulated NK cells retained selective cytotoxic activity since they continued to remain incapable of lysing uninfected target cells. MCMV-infected rat heart fibroblasts induced more interferon and were also more susceptible to NK activity than MCMV-infected mouse embryo fibroblasts. In spite of this difference in interferon-inducing capacity, there was no augmentation of cytotoxicity of MCMV-infected mouse embryo fibroblasts when mouse splenocytes were cocultivated with both target cells. Finally, when production of interferon in the NK reaction was inhibited by the addition of actinomycin D, no reduction of NK activity was seen. Our findings suggest that native mouse NK cells can discriminate between MCMV-infected cells and uninfected cells, this ability leading to the selective lysis of the virus-infected cells. Furthermore, although we could demonstrate augmentation of NK activity by interferon, interferon activation of NK cells may not be a necessary precondition for the development of endogenous NK activity.

Animals↗
PubMed1982

Tumor-promoting diterpene esters prevent macrophage activation and suppress macrophage tumoricidal capacity.

The efficacy of varied diterpene ester type tumor promoters in suppressing the acquisition as well as the manifestation of cytolytic activity by macrophages was investigated. These mechanisms, believed to be basic to natural antitumor resistance, were markedly suppressed not only by the phorbol ester, TPA, but also by several other tumor promoters of the polyfunctional diterpene ester type covering tigliane, ingenane, and daphnane derivatives. The promoters were particularly effective in preventing the lymphokine-induced enhancement of natural cytolytic activity in resting macrophages. Moreover, the same promoters suppressed the manifestation of cytotoxicity by previously activated macrophages. Their influence on the effector phase was less pronounced than on the activation phase. In sharp contrast, typical solitary carcinogens of the polycyclic aromatic hydrocarbon type exerted little or no activity in the macrophage test systems. Since TPA had already been shown to suppress the natural killer activity in vitro and to abrogate host tumor resistance in vivo, the present findings lend further support to the interpretation that tumor promoters, apart from directly stimulating the outgrowth of transformed cells, may function via interference with natural antitumor effector systems.

Animals↗
PubMed1982

Tumor-promoting phorbol esters induce macrophage differentiation from bone marrow precursors.

The tumor-promoting phorbol diester, 12-0-tetradecanoyl-phorbol-13-acetate (TPA), induces in liquid cultures of rat and mouse bone marrow cells a sequence of events strikingly similar to those initiated by colony-stimulating activity known to regulate growth. Changes include stimulation of DNA synthesis and induction of cell proliferation, enhancement of adherence to the substratum, increase in lysozyme secretion, the expression of plasma membrane receptors for the Fc portion of IgG and the capability of manifesting lymphokine-induced, immunologically nonspecific long-term cytotoxicity. These findings indicate that TPA selectively stimulates precursors of the mononuclear phagocyte lineage to proliferate and to differentiate into macrophages, thus mimicking the effects of macrophage colony-stimulating activity.

Animals↗
PubMed1982

Structure of the linkage-region between polysaccharide chain and core protein in bovine corneal proteokeratan sulfate.

Peptidokeratan sulfate from bovine cornea was degraded by a combination of desulfation, exo-enzymic digestion and finally digestion with endo-beta-N-acetylglucosaminidase D. The same procedure was carried out both with [3H]fucose-labelled and [3H]mannose-labelled peptidokeratan sulfate. Data obtained by methylation analysis of peptidokeratan at the different degradation steps, as well as action of endo-beta-N-acetylglucosaminidase D, showed that the binding-region in proteokeratan sulfate from bovine cornea is identical with a structure found in various GlcNAc(beta 1-N)-Asn-linked mannosyl glycoproteins. The existence of a chitobiose unit between asparagine and mannose was proved by action of endo-beta-N-acetylglucosaminidase D. The existence and position of an (alpha 1 leads to 6)-linked fucosyl residue at the Asn-bound GlcNAc was demonstrated by action of alpha-fucosidase, endo-beta-N-acetylglucosaminidase D and by gel chromatography on Bio-Gel P-4. By gas chromatography/mass spectrometry studies, the existence of a 1,4,6-trisubstituted beside a 1,4-disubstituted GlcNAc in the binding-region oligosaccharide was shown. Other results reported here are according to analytical data previously published (Keller, R., Stein, T., Stuhlsatz, H.W., Greiling, H., Ohst, E., Müller, E. & Scharf, H.-D. (1981) Hoppe-Seyler's Z. Physiol. Chem. 362, 327-336).

Acetylglucosamine↗
PubMed1982

Prevention of interferon-induced augmentation of cellular antitumor effector mechanisms by phorbol esters.

Both natural killer cell- and macrophage-mediated spontaneous in vitro cytotoxicity for tumor targets is rapidly and strongly augmented by interferon. Macrophage-activating lymphokines considerably enhance macrophage-tumoricidal activity but did not affect natural killer cell-type cytotoxicity. Augmentation of cytolytic capacity by interferon and by macrophage-activating lymphokines is prevented by the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate. However, the classical antiviral activity and the specific binding of interferon to cell surface receptors remains unaffected by 12-O-tetradecanoylphorbol-13-acetate.

Animals↗
PubMed1982

Suppression of natural tumor resistance by tumor promoters.

The findings of the present and other studies (4,7) show that TPA and other tumor-promoting esters suppress various in vitro manifestations of natural cell-mediated tumor resistance: (a) prevention of enhancement of macrophage cytocidal activity; (b) suppression of cytocidal capacity by activated macrophages; and (c) suppression of cytolytic activity of NK cells. Moreover, they abrogate host tumor resistance in vivo. These suppressive effects of tumor promoters on natural antitumor effector systems may constitute a fundamental mechanism in carcinogenesis.

Animals↗
PubMed1981

[Chylothorax associated with sarcoidosis].

Chylothorax with bilateral hilar and mediastinal lymphomas has been observed in a 27-year-old patient. Further clinical investigations revealed sarcoidosis with involvement of the mediastinal lymphnodes, the bronchial mucosa and the pleural mesothelium. It is suggested that the chylothorax is a complication of sarcoidosis, although pleural effusions of chylus have thus far been reported only in traumatic or malignant diseases of the mediastinum. The pathogenesis was unclear until exploration of the pleural space by thoracoscopy showed an intact and unaffected thoracic duct. During longterm treatment with corticosteroids, supported by several pleural drainages, the chylothorax and other concomitant symptoms gradually regressed.

Adrenal Cortex Hormones↗
PubMed1981

[A "micro" technique for arterial blood gas analysis].

Puncture of the radial or cubital artery with a thin needle of 0.4--0.5 mm diameter connected to a glass capillary is a simple and non-invasive technique for obtaining samples for arterial blood gas analysis. Compared with the conventional sampling techniques using glass syringes and needles of larger calibers, the results, especially with regard to paO2 values, show very close agreement over a wide range from hypoxic to hyperoxic conditions (correlation coefficient r2 = 0.99) if the microsamples are analysed within 10 minutes. Delayed analysis after 30 minutes, however, shows marked underestimation of hyperoxic paO2 (greater than 150 mm Hg) with the microtechnique, whereas paO2 values below 100 mm Hg are still comparable to the macrosamples. The method described provides an accurate arterial blood gas analysis without discomfort or harmful side effects, especially in patients under treatment with anticoagulants.

Arteries↗