Modern pharmaceutical biotechnology. Situation worldwide and in Germany 1995.

A variety of new diagnostics and drugs have been developed with the aid of modern biotechnology which has opened up new medical possibilities and will yield novel solutions in the future. The remarkable dynamics of the innovation process in the pharmaceutical sector is reflected by the number of drugs under development. In 1995, 771 projects were known to be in development worldwide.

A method for the quantitation of interleukin-2 activity.

A bioassay for the determination of interleukin-2 activity is described. We have compared the traditional method of data processing, which involves probit analysis and curve fitting, with a simpler method based on the so-called AUC (area under the curve). The latter method is readily applicable to spreadsheet software and can handle large amounts of data.

Inhibition of HIV and virus replication by polysulphated polyxylan: HOE/BAY 946, a new antiviral compound.

Xylanpoly-(hydrogen sulphate) disodium salt with a molecular weight of about 6000 daltons (HOE/BAY 946) completely inhibited syncytium formation induced by the infection of T lymphocytes with HIV as well as viral replication at concentrations above 25 micrograms/ml. This dose was found to be inhibitory for several strains of HIV-1 and HIV-2. Low molecular weight fractions of the compound were less active against HIV, and high molecular derivatives were as active as HOE/BAY 946.

Monitoring of interleukin-2 receptor (IL-2R) expression in vivo and studies on an IL-2R-directed immunosuppressive therapy of active and adoptive adjuvant-induced arthritis in rats.

Recent evidence indicates that adjuvant arthritis (AA) of rats induced by complete Freund's adjuvant (CFA) is an autoimmune disease that is mediated by T cells. This report describes the distribution of activated IL-2 receptor (IL-2R)-bearing cells in spleen, popliteal lymph nodes (PLN) and blood in AA rats and in naive healthy rats using the monoclonal antibody (mAb) ART-18. It was found that in the primary lymph nodes (injected side) two peaks of elevated numbers of IL-2R-positive cells (Day 9/10 with a 40-fold increase; Day 25 with a 75-80-fold increase) occur.

Production of human monoclonal antibodies from immobilized cells in the Opticell culture system.

An EBV-transformed human B cell line, which produces monoclonal IgM antibodies, was cultured in an immobilized state on a ceramic matrix in the Opticell system. Cell growth, metabolic activity and product formation of these cells were optimized in a single semi-continuous culture of 10 inductions for 29 d. All in all, 19.

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.

Cultivation of Bowes melanoma cells in the Opticell system: influence of the addition of protein supplements to the serum-free medium on the production of plasminogen activator.

The influence of a protein-free and a protein-rich, supplemented serum-free medium on the production of plasminogen activator (t-PA) from Bowes melanoma cells was investigated in the Opticell culture system and compared to tissue culture flask cultures. In the presence of medium supplements metabolic activity and t-PA production were favoured in both systems. The addition of supplements was apparently more effective in the Opticell than in flask cultures, because t-PA activity obtained in the Opticell was 2-3 times higher in protein-rich medium, but 2 times lower in unsupplemented medium than in flasks.

A screening method to develop serum-free culture media for adherent cell lines.

A screening method was established to develop chemically defined, serum-free culture media for human adherent cell lines. It indicates within 2-6 months whether a certain cell line is suited for routine cultivation under serum-free conditions, and which medium supplements and surface coatings of the culture vessels the cells need for minimal demand. This method was tested with the human cell lines Bowes melanoma and prostate carcinoma 3 (PC 3).

Pseudo-allergic reactions to drugs and chemicals.

Drugs can interfere with the immune system in two basically different ways: (1) they may interact with the specific recognition mechanisms of the immune system and thus induce an allergic response that is specific for the offending agent; (2) drugs may exert pharmacological effects on the immune systems which result in a response that is independent of its recognition structures or they may activate effector and amplification mechanisms that are normally triggered by specific immune processes. Allergic reactions to drugs are different from reactions that exhibit the same clinical symptoms but lack the specificity of an allergic reaction to the offending agent. It has been suggested that those non-specific reactions which mimic the signs and symptoms of allergic reactions should be classified as pseudo-allergic reactions (PAR).

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.

The pathomechanism of acetylsalicylic acid intolerance. A hypothesis.

In a number of individuals suffering from chronic asthma or chronic urticaria, acetylsalicylic acid and structurally unrelated non-steroidal anti-inflammatory agents and other compounds, e.g. tartrazine, elicit an intolerance syndrome that mimics the signs and symptoms of an immediate-type allergic (anaphylactic) reaction.

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.

[Cell kinetics in experimental rheumatoid lesions and application in antirheumatic drug research (author's transl)].

The kinetics of chronic inflammatory cellular infiltrates in antiglobulin-induced arthritis, peritonitis and subcutaneous fibrin granuloma were investigated. Only small numbers of the mononuclear cells were labeled after 3H-thymidine impulse labeling, whereas a high labeling index results after 3H-thymidine labeling of the bone marrow. It is concluded that in experimental arthritis the inflammatory so-called cellular hyperplasia consists in bone marrow derived mononuclear cells.

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.

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.

Immunogenicity of aryl esters of salicylic or acetylsalicylic acid in guinea pigs.

A variety of derivatives of acetylsalicylic and salicylic acid have been investigated for their immunogenic properties in guinea pigs including salicylsalicylic acid (SSA), acetylsalicylsalicylic acid (ASSA), disalicylide (DI), trisalicylide (TRI), acetylsalicylic acid paracetamol ester (ASPE) and acetylsalicylic acid guajacol ester (ASGE). Contact sensitivity could be elicited by the sensitizing agent, however, with acetylsalicylic acid anhydride (ASAN) a more pronounced contact reaction could consistently be observed. Systemic anaphylactic reactions elicited by intravenous injection of N-salicyloyl bovine serum albumin could only be induced by ASAN, DI, TRI and ASSA, whereas SSA, ASPE and ASGE did not induce an anaphylactic state at a comparable dose level.