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Biomedical subjects

G G Steinmann

Publications and source records attributed to G G Steinmann.

13 recordsLinked to original sources
PubMed2001

Immunopharmacological in vitro effects of Eleutherococcus senticosus extracts.

The objective of these investigations was to further elucidate the immunopharmacological profile of fluid extracts of Eleutherococcus senticosus and to identify the specific role of its characteristic eleutherosides B and E. An ethanolic dry extract of Eleutherococcus senticosus was used as starting material for the isolation of the eleutherosides B and E. Immunopharmacological studies included expression of major histocompatibility complex class I and II molecules by rat bone marrow-derived mononuclear phagocytes, human lymphocyte marker flow cytometry, and in vitro testing of human lymphocyte functions. In contrast to the isolated eleutherosides B and eleutherosides E and the re-mixed eleutherosides B and E, the whole ethanolic fluid extract of Eleutherococcus senticosus was able to induce and enhance interleukin-1 and interleukin-6 but not interleukin-2 production in vitro. The effective concentration of the whole ethanolic extract ranged from 1.0-0.1 mg/ml for the enhancement of interleuking-1 alpha production and 1.0-0.03 mg/ml for the enhancement of interleukin-6 production. It is concluded that the observed enhancing immunopharmacological activities on acute phase response mediators are best exhibited by the induction with whole ethanolic extracts whereas the species-specific and characteristic eleutherosides B and E are not associated with these activities.

Adjuvants, Immunologic↗
PubMed1998

Interferon-gamma in the prevention of severe burn-related infections: a European phase III multicenter trial. The Severe Burns Study Group.

OBJECTIVES: To determine the efficacy and tolerance of interferon-gamma-1b (IFN-gamma) for the prevention of death related to infection in patients with burn injury who were at risk for infection. The positive anti-infective effects of IFN-gamma observed in animal models and in clinical studies provided the rationale for this study. DESIGN: Randomized, double-blind, placebo-controlled, phase III multicenter trial, with a group sequential design, conducted at 23 European burn centers. PATIENTS: Two hundred sixteen patients with major critical burn (Abbreviated Burn Severity Index score of > or = 7). INTERVENTION: Patients were randomized to receive IFN-gamma (100 microg) or placebo daily by subcutaneous injection for up to 90 days. MEASUREMENT AND MAIN RESULTS: The primary end point (the incidence of death related to infection within 90 days from the start of treatment) was similar in the two treatment groups. There were no significant differences between the two treatments in any of the secondary end points (all causes of mortality at 90 days, incidence of infectious complications, duration of intensive care unit or hospital stay, and scar formation at 90 days). CONCLUSION: IFN-gamma did not protect burn patients from infections or decrease the mortality from infections.

Adult↗
PubMed1996

Rationale, design and performance of a clinical trial to investigate interferon-gamma (Imukin) in the prophylactic treatment of severe burns-related infections.

Recent advances in resuscitation therapy have increased the survival rate of patients with severe burns in the burn shock phase. Infectious complications represent the major cause of death in patients with extensive burns, however, in spite of the application of early and aggressive interventions. Extensive burn injury causes profound alterations in various essential elements of the normal host immune response and the main aim of treatment after resuscitation is to maintain or even improve host resistance. The positive anti-infective effects of interferon (IFN)-gamma observed in animal models and in clinical studies, for example in chronic granulomatous disease, provided the rationale for a study to investigate its use in patients with severe burns. A study was therefore designed to determine the efficacy and tolerance of IFN-gamma in preventing death related to infection in patients with severe burn injury who are at risk of infection. In order to avoid unnecessary risk for patients and reduce the cost, a sequential design was chosen. The primary end-point was reviewed in a group sequential manner after every 60 patients through an independent monitoring board. The study was a randomised, double-blind, Phase III multi-centre trial, conducted at 23 European Burn Centres. An interval censored survival time approach was taken, using information collected at days 8, 15, 30, 60, and 90. The trial is still blinded, but the rationale for conducting the study and its design are discussed.

Burns↗
PubMed1992

Low incidence of antibody formation due to long-term interferon-alpha 2c treatment of cancer patients.

In order to study the long-term immunogenicity of interferon-alpha 2c (Berofor) in cancer patients, serum was collected starting in 1983 from study patients with various proliferative diseases who received interferon-alpha 2c at different doses, according to different schedules, and via different routes. A total of 1992 samples were tested for the presence of anti-interferon-alpha 2c antibodies. Due to long-term interferon-alpha 2c treatment, 346 patients were eligible for induction of neutralizing anti-interferon antibodies over a treatment period of 2-52 months. Most patients were treated for longer than 6 months. Of the 346 patients, three patients (0.87%) exhibited measurable titers of neutralizing antibodies following therapy with interferon-alpha 2c. One hundred and sixty-three patients suffered from non-Hodgkin lymphomas, leukemias, and preleukemias. One patient with chronic myeloid leukemia experienced antibody induction under therapy. The other 183 patients had solid tumors. Two of them reacted with antibody production. All titers were very low (1:12, 1:8, and 1:64). Compared with figures reported for other interferon-alpha preparations, the propensity of interferon-alpha 2c to induce neutralizing antibodies seems to be very low. This property might be related to arginines occurring as critical residues in positions 23 and 34 of the interferon-alpha 2c molecule.

Antibody Formation↗
PubMed1989

A rapid in vitro method for the evaluation of potential antitumor drugs requiring metabolic activation by hepatic S9 enzymes.

Metabolic activation is a prerequisite for the antitumor activity of certain drugs such as cyclophosphamide. In vitro assays require systems for metabolic activation to reveal the toxicity of such compounds for tumor cells. Although a number of methods utilizing systems for the in vitro metabolic activation of drugs have been published, practical assays applicable to large scale screening for such agents have been lacking. We, therefore, now report that incorporation of a liver subcellular fraction (S9) into a recently established cell growth inhibition assay (microculture tetrazolium assay) significantly increased the cytotoxicity of cyclophosphamide. Under optimal conditions, the 50% growth inhibitory concentration was decreased in the presence of S9 from more than 600 micrograms/ml to less than 4 micrograms/ml, depending upon the cell line. The method also proved suitable for studies investigating metabolic detoxification (enzymatically or non-enzymatically) by conjugation reactions. For example, glutathione (5 mM) markedly reduced the cytotoxicity of activated cyclophosphamide. In contrast, the addition of UDP glucuronate (10 mM) in the presence of the UDP-glucuronosyltransferase activator UDP-N-acetylglucosamine (10 mM) had little effect on cyclophosphamide toxicity.

Animals↗
PubMed1986

Immunohistochemical characterization of the thymic microenvironment. A light-microscopic and ultrastructural immunocytochemical study.

The epithelial framework of the human thymus has been studied in parallel by immunohistochemical methods at the light- and electron-microscopic levels. Different monoclonal antibodies were used, reacting with components of the major histocompatibility complex, keratins, thymic hormones and other as yet antigenically undefined substances, which show specific immunoreactivities with human thymus epithelial cells. The electron-microscopic immunocytochemical observations clearly confirm microtopographical differences of epithelial cells not only between the thymic cortex and medulla, but also within the cortex itself. At least four subtypes of epithelial cells could be distinguished: 1) the cortical surface epithelium; 2) the main cortical epithelial cells and thymic nurse cells; 3) the medullary epithelial cells; and 4) the epithelial cells of Hassall's corpuscles. The various epithelial cell types of the thymus display several common features like tonofilaments, desmosomes and some surface antigens as demonstrated by anti-KiM3. In other respects, however, they differ from each other. The cortical subtype of thymic epithelial cells including the thymic nurse cells shows a distinct pattern of surface antigens reacting positively with antibodies against HLA-DR (anti-HLA-DR) and anti-21A62E. Electron-microscopic immunocytochemistry with these antibodies clearly reveals a surface labeling and a narrow contact to cortical thymocytes particularly in the peripheral cortical regions. An alternative staining pattern is realized by antibodies to some antigens associated with other subtypes of thymic epithelial cells. Medullary epithelial cells as well as the cortical surface epithelium react likewise positively with antibodies to special surface antigens (anti-Ep-1), to special epitopes of cytokeratin (anti-IV/82), and to thymic hormones (anti-FTS). The functional significance of distinct microenvironments within the thymus provided by different epithelial cells is discussed in view of the maturation of T-precursor cells.

Antibodies, Monoclonal↗
PubMed1985

The involution of the ageing human thymic epithelium is independent of puberty. A morphometric study.

One hundred and thirty-six thymuses completely removed at autopsy from persons suffering a sudden death were examined by stereological and morphometrical methods. Adding biopsy material from immunologically healthy cardiac patients we obtained relative volumes from 204 persons ranging in age from 1 month to 107 years. The size of the human thymus remains unchanged during ageing under normal physiological conditions (median: 19.5 cm3). Individual maximum size (range: 5-70 cm3) is reached in the first year of life. Early histological changes are in the enlargement of the perivascular space, the Hassall's bodies, and the connective tissue. This begins in the first year of life, reaches a maximum from 10 to 25 years, then declines again. Adipose tissue replaces the lymphocytic perivascular space and the connective tissue only. This occurs extensively after the age of 15 years. When defined by the silver impregnation technique, the volumes of the thymic epithelium (cortex and medulla), show a continuous involution from the first year to the end of life. The curve can be approximated to simple negative logarithmic functions. The velocity and nature of involution of the thymic epithelium do not change under the influence of the changing hormonal balance due to puberty. Since important thymic functions (T lymphopoiesis and T-cell differentiation) are located in the epithelial space, the age-related involution of the human thymus is not related to puberty.

Adipose Tissue↗
PubMed1984

Admission criteria for immunogerontological studies in man: the SENIEUR protocol.

Immunogerontological studies in man have often led to conflicting results. One of the main reasons is the selection of the subjects to be studied. Admission criteria such as "apparently healthy" or "without overt disease" seem insufficient to exclude underlying disease which might influence the immune system and thereby the results. In an attempt to solve this problem, the SENIEUR protocol described in this paper was developed by a working party in the framework of the EURAGE Concerted Action Programme on Ageing of the European Community. This protocol establishes strict admission criteria for immunogerontological studies in man based on clinical information and laboratory data, and it sets limits to pharmacological interference. The use of this protocol will lead to standardization between centers and also to a closer study of the influence of age as such on the immune system. These findings in the immunologically "optimally aged" can also serve as reference values for immunogerontological studies in subjects who do not meet the SENIEUR criteria. In this way the use of this protocol can contribute to the dissection of the influence of disease versus ageing on the immune system.

Adult↗
PubMed1984

Immunohistological demonstration of terminal transferase (TdT) in the age-involuted human thymus.

By using a sensitive immunoperoxidase technique, serological determinants of terminal deoxynucleotidyl transferase (TdT, E. C. 2.7.7.31) were found in cortical lymphocytes of thymus biopsies of adult and aged persons (21-70 years) of both sexes. In contrast to biochemical determinations, specific immunohistological studies showed that TdT is continuously present in very large numbers of cortical thymic lymphocytes during human life, despite subtotal physiological involution of the thymus.

Adolescent↗