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Biomedical subjects

H G Opitz

Publications and source records attributed to H G Opitz.

At least 19 recordsLinked to original sources
PubMed1991

Antitumor activity of Ilmofosine (BM 41.440) in the 3Lewis-lung carcinoma model.

Ilmofosine (1-hexadecylthio-2-methoxymethyl-1,3-propanediol-phosphocholine, BM 41.440) is a thioether phospholipid with cytostatic/cytotoxic properties. The antineoplastic activity of this compound was investigated in vivo in the 3Lewis-lung carcinoma system. 3Lewis lung tumor-bearing C57Bl/6 mice were treated with 0.625 to 40 mg Ilmofosine/kg per day p.o. either from days 1 to 9 or from days 11 to 28 after intrafoot-pad tumor cell inoculation. Ilmofosine caused a significant dose-related response on tumor growth and metastases, expressed in terms of tumor diameter, tumor weight, survival time and number of metastases-free animals as compared to sham-treated and positive (cyclophosphamide) controls. The results suggest that direct cytostatic/cytotoxic effects, rather than immune-modulatory mechanisms, preferentially contribute to the antitumor activity of Ilmofosine in vivo.

Animals↗
PubMed1990

In vivo antitumor activity of ilmofosine.

Ilmofosine is a cytostatic/cytotoxic thioether phospholipid derivative. The in vivo anti-tumour activity of this compound was investigated in a methylcholanthrene (MethA)-induced fibrosarcoma and in the 3Lewis-lung carcinoma systems, respectively. Ilmofosine showed antineoplastic and antimetastatic properties at oral doses ranging from 0.625 to 40 mg/kg/day. Combination of Ilmofosine (p.o.) together with either cyclophosphamide (p.o.) or cis-DDP (i.v.) resulted in synergistic effects in vivo. These results demonstrate the in vivo antitumour activity of Ilmofosine in two tumour systems. The data indicate that direct cytostatic/cytotoxic effects of Ilmofosine are mainly responsible for its antitumour activity in vivo and which are increased by other cytotoxics.

Animals↗
PubMed1987

Monoclonal antibodies detecting plasminogen activators on the membrane of leukemic lymphoid cells of T-cell origin.

The specificities of six monoclonal antibodies produced against plasminogen activator of the human Bowes melanoma cell line are described. They have been used to detect membrane-bound plasminogen activator on cultured human lymphoid cell lines and in neoplastic human lymphocytic and myeloid cells of leukemic patients. These studies indicate that only certain phenotypic subsets of the T-cell lineage derived from patients with chronic lymphocytic leukemia or with Szezary syndrome express plasminogen activator on their surface membrane.

Animals↗
PubMed1982

Clearance of interleukin 2 from the blood of normal and T cell-depleted mice.

Partially purified, concentrated interleukin 2 (IL 2) was injected i.v. into normal and T cell-depleted mice. At various times after injection IL 2 was determined in the sera of these mice. An interference with the test by a potential inhibitor of IL 2 in the serum was excluded. Il 2 was cleared equally rapidly, with a half-life of 3 min, from the blood of both groups of mice. It is concluded that IL 2 is a short-range mediator under physiological conditions, and that clearance was not due to adsorption to T cells.

Animals↗
PubMed1982

The thymus as primary site for antigen-specific T suppressor cells in neonatally induced tolerance to bovine serum albumin.

The ontogeny of antigen-specific T suppressor cells in thymus and spleen was analyzed in CBA/Ca mice which were rendered tolerant as neonates by subimmunogenic doses of bovine serum albumin (low-zone tolerance). Activity of T suppressor cells from those mice was assessed by an assay in which spleen cells from animals primed with fluorescein-conjugated human gamma globulin can be stimulated in vitro to produce IgG anti-fluorescein antibodies when cultured in the presence of fluorescein-conjugated bovine serum albumin. Carrier-specific T suppressor cells appear first in the thymus (day 10), and much later (day 30) in the spleen. The data are discussed in connection with the possible role of T suppressor cells during induction of tolerance in newborn mice.

Animals↗
PubMed1982

A new model for investigations of T-cell functions in mice: differential immunosuppressive effects of two monoclonal anti-Thy-1.2 antibodies.

Two monoclonal anti-Thy-1.2 antibodies were investigated for their activity in eliminating T cells in vitro and in vivo. Both antibodies exert a complement-dependent cell cytotoxicity in vitro. Antibody B that belongs to the IgM class shows a 100-fold higher complement-dependent cytotoxic activity than antibody C, which is of IgG2a class. However, administration of antibody C into Balb/c mice results in the elimination of T cells as determined by the failure of different T-cell functions. Within 24 hours after administration of antibody C, the reactivity of spleen of lymph-node cells to T-cell mitogens, the antibody response to the T-cell-dependent antigen SRBC and the SRBC-induced delayed-type hypersensitivity are completely abolished. These effects are dose-dependent in a dose range of 0.1-1.0 mg Ig protein per animal and affects only T cells in the peripheral lymphoid organs. The Thy-1.2-bearing cells residing in the thymus are not impaired by the treatment of the animals with this monoclonal antibody and are able to repopulate the peripheral lymphoid organs within 30 to 60 days. Investigations into the mode of action of the removal of peripheral T cells revealed that antibody-C-coated Thy-1.2-bearing cells are rapidly phagocytosed by macrophages, while antibody-B-coated Thy-1.2-bearing cells are not. This might be the reason for the differential in-vivo activities of the two monoclonal antibodies. A model with new qualities for the study of functions and the regeneration of T cells in vivo has been established.

Animals↗
PubMed1981

T-lymphocyte colony formation of murine spleen cells in a one-stage micro agar culture.

A one-stage agar culture technique for stimulation of T-lymphocyte colony-forming units (TL-CFU) derived from murine spleen cells is described. The cultures are in glass capillaries in a volume of 30 microliter. Both, phytohemagglutinin (PHA) and concanavalin A (Con A) stimulate growth of TL-CFU. The technique does not require prestimulation of lymphocytes in liquid culture or addition of growth factor(s). The most important requirements for optimal colony growth are a low concentration of agar (less than 0.1%) and the appropriate number of seeded cells (60 X 10(3) per culture). This one-stage micro agar culture is economical and easily handled. Many cultures can be prepared and rapidly evaluated. The plating efficiency is about 10 colonies per 10(4) nucleated spleen cells. The T-cells character of the TL-CFU was demonstrated by treatment of the spleen cells with a monoclonal anti-Thy-1.2 antibody (anti-Thy-1.2) and complement before assaying for colony growth and also by staining the cells in the cultures with anti-Thy-1.2-FITC. Growth characteristics of TL-CFU indicate that cell interactions are operative during activation and proliferation. The nature of the cells cooperating in this system is discussed.

Agar↗
PubMed1979

Macrophages/monocytes require cell-to-cell contact in order to regulate the growth of a murine lymphoma cell line.

The mechanism of the macrophage-regulated proliferation of the murine lymphoma cell line FIO 30 has been further investigated. It appears that the macrophage is alone in its ability to support FIO 30 growth; a macrophage-like cell line, however, is unable to provide the stimulus required by the FIO 30 cells for their proliferation. Investigations into the nature of this stimulus indicate that the serum factor pro-MaSF and a macrophage cell surface component act synergistically to support the growth of the FIO 30 cell, but only when the two cell types are in close promixity. MaSF has also been further characterized and is shown to be closely associated with serum albumin.

Animals↗
PubMed1978

Promotion of L1210 tumour growth by macrophages.

Low numbers (10(4)) of peritoneal exudate L1210 mouse lymphoma cells were injected into DBA/2 mice subcutaneously and the development of tumours was followed. Tumour takes occurred in 100% of the animals within 9 days after tumour transplantation. The latent period of tumour development was prolonged by 6-10 days when tumour cells of the peritoneal exudate, depleted of adherent/phagocytic cells, were used in the inoculum or when tumour cells derived from continuous cell cultures were used. Addition of adherent cells in high numbers to in-vitro-derived L1210 cells accelerated tumour growth. This effect was found to be not specific for adherent/phagocytic cells, as liver cells had the same influence on tumour growth. It is concluded that, under certain experimental conditions, a cell population with the functional properties of macrophages is able to promote tumour development, most likely due to their non-specific effect on the micro-environment of the growing tumour.

Animals↗
PubMed1977

The role of fetal calf serum in the primary immune response in vitro.

The mode of action of 2-mercaptoethanol (2-ME) on the primary immune response in vitro was investigated. Fetal calf serum (FCS) was preincubated with 2-ME and lyophilized to remove free 2-ME. This 2-ME-treated FCS was able to substitute the function of adherent cells in the primary immune response against sheep red blood cells (SRBC) in vitro; Fractionation of 2-tme-treated FCS on a Sephadex G-100 column showed that 2-ME acted on a high molecular serum component which after activation, could substitute for macrophages. In order to obtain a humoral immune response against SRBC in vitro, spleen cells require selected FCS. These "good" sera could be distinguished from "deficient" sera by their higher content of this 2-ME-activated factor. The height of the in vitro immune response to SRBC was dependent on the amount of activated factor added to the culture medium. FCS normally required in the culture medium could be completely replaced by the factor-containing fraction without deleterious effect on the culture medium. The factor should be added to the spleen cells during the first 24 h of culture and remain there for 72 h in order to obtain an optimal immune response. The factor could be partially absorbed by spleen cells but not by SRBC. The relationship between macrophage, 2-ME, and FCS in eliciting an in vitro primary immune response is discussed.

Antibody Formation↗
PubMed1977

Growth regulation of a murine lymphoma cell line by a 2-mercaptoethanol or macrophage-activated serum factor.

A mouse lymphoma cell line has been established that is dependent for growth on the presence of an activated serum component. This growth factor is found in an inactive form in fetal bovine serum (FBS) and can be activated by 2-mercaptoethanol and by macrophages. A factor-containing fraction can be separated from FBS by Sephadex G-100 chromatography and once activated, can be used as a substitute for whole serum in the culture medium without adverse effect on the cell growth. The significance of these findings with respect to the study of the immune response and cancer research is discussed.

Animals↗
PubMed1977

Humoral primary immune response in vitro in a homologous mouse system: replacement of fetal calf serum by a 2-mercaptoethanol or macrophage-activated fraction of mouse serum.

The primary immune response in mouse spleen cell cultures against heterologous red cell antigens is dependent on the medium being supplemented with selected batches of fetal calf serum. Mouse serum itself is not able to support this response. The active immune response-supporting component in fetal calf serum seems to be a distinct factor (s), which has been partially purified by Sephadex G-100 filtration and termed MaSF-2-mercaptoethanol-activated serum factor. In this report it is demonstrated that MaSF is also present in mouse serum. For functional detection, mouse MaSF has to be separated from higher m.w. inhibitors, and has to be activated by 2-ME. After separation and activation mouse MaSF can support the primary immune response in a completely homologous in vitro culture system. Evidence is presented that MaSF can also be activated by macrophages. It is concluded that macrophages and 2-ME have the same mode of action in the primary immune response in vitro, i.e., induction of lymphocyte competence by activation of a serum factor.

Animals↗
PubMed1976

Polyclonal stimulation of lymphocytes by macrophages.

To analyze the interaction between macrophages and splenic lymphocytes with reference to time and concentration, the Mishell-Dutton system was divided into two experimental steps. Step 1 consisted of the cocultivation of spleen cells with various doses of macrophages for different periods of time, while in step 2 macrophages were removed, spleen cells transferred to fresh petri dishes and cultivated until plaque assay. Cocultivation of spleen cells with high doses of macrophages for 4--8 h markedly enhanced the DNA synthesis and plaque-forming cell (PFC) response of sheep red blood cell-stimulated and unstimulated cultures. A cocultivation longer than 24 h resulted in an inhibition of both DNA synthesis and PFC response of spleen cells. These studies suggest a nonspecific function of macrophages on proliferation and differentiation processes in antibody formation.

Animals↗
PubMed1976

The role of adherent cells in the immune response. Fibroblasts and products released by fibroblasts and peritoneal cells can substitute for adherent cells.

The primary immune response to sheep erythrocytes in adherent cell-depleted cultures was restored by adding a critical number of peritoneal cells. Complete substitution was achieved also with supernatants from allogeneic and syngeneic peritoneal cells. Both living fibroblasts and supernatants from fibroblast cultures were found to be highly efficient substitutes for adherent cells in both syngeneic and allogeneic systems. Supernatants from non-antigen-reated peritoneal cells and fibroblasts caused increased DNA synthesis and induction of polyclonal antibody synthesis in normal spleen cells. Thus, adherent cells need not function in the immune response by presenting antigen to the B cells via 'IgT' or by releasing signal-2 activity, which acts on lymphocytes that have already received signal 1.

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