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Biomedical subjects

R Saller

Publications and source records attributed to R Saller.

At least 73 records · Page 4Linked to original sources
PubMed1999

Selective modulation of phosphatidylserine exposure on subpopulations of human peripheral blood lymphocytes by a plant lectin, Viscum album agglutinin (VAA)-I and its recombinant form (rVAA) in vitro.

Growing evidence suggests that lectin-carbohydrate interactions are involved in the regulation of the balance between cell growth and programmed cell death. Viscum album agglutinin (VAA)-I is a galactoside-specific, type II ribosome-inactivating plant lectin. At concentrations less than 10 ng/ml, VAA-I has been shown to induce gene expression and secretion of proinflammatory cytokines as well as apoptosis in cultures of human peripheral blood mononuclear cells (PBMC). This study analyzes the effects of VAA-I and its recombinant nonglycosylated form (rVAA) on alterations of cell membrane permeability of cultured human peripheral lymphocytes (PBL) and on membrane exposure of phosphatidylserine characteristic of apoptosis. Analyses were performed by flow cytometry after staining with propidium iodide (PI) and/or with FITC-Annexin V/PI. After 24 h incubation of PBMC with 100 ng/ml VAA-I and rVAA, staining with supravital concentration of PI (20 microg/ml) for 1 h revealed no differences in percentages of PI-positive cells induced by the two forms of lectin (32.3% and 29.4%), but the exposure to 5 microg/ml PI for 15 min resulted in a significant difference: 35.1% and 8.0% after VAA-I and rVAA treatment, respectively. Kinetic analysis of membrane alterations showed mainly Annexin V positivity after 24 h, whereas after 48 h and 72 h incubation with 100 ng/ml VAA-I or rVAA loss of membrane integrity occurred, as demonstrated by PI staining. Similar to VAA-I, rVAA showed a higher binding affinity for monocytes and granulocytes than for lymphocytes. In cultures of PBL, the binding rank order of both lectins to lymphocyte subsets was NK, CD19+ > CD8+ > CD4+. The amount of Annexin/PI staining of PBL subsets corresponds to the degree of their binding capacity. In conclusion, present results demonstrate that VAA-I and its nonglycosylated recombinant form rVAA exhibit comparable effects on cell membrane alterations in the subsets of human PBLs.

Annexins↗
PubMed1999

[Mistletoe therapy from the pharmacologic perspective].

Because of their cytostatic/apoptotic and immunomodulatory effects mistletoe extracts are often applied in tumour patients. Recent experimental data suggest that the mistletoe lectins Viscum album agglutinin (VAA)-I and -II are play an important role in the efficacy of mistletoe therapy. VAA-I and -II are members of the type-II ribosome-inactivating proteins. VAA-I has been shown to induce cytostatic effects in cultures of various eukaryotic cells in vitro. In 24-hour cultures of human peripheral lymphocytes, flow-cytometric investigations with propidium iodide (PI) in hypotonic buffer and quantitative assessment of DNA breaks with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay were carried out; they revealed a dose-dependent VAA-I-induced apoptosis (lectin concentrations between 10 ng/ml and 1 microg/ml). In 24-hour cultures of peripheral blood mononuclear cells (PBMC), VAA-I in non-cytotoxic concentrations (1+/-10 ng/ml) induced mRNA expression and enhanced the secretion of proinflammatory cytokines. The stimulation of NK cells by VAA-I in vitro was enhanced in additive manner by the combination of VAA-I with IL-2 and IL-12. In culture of PBMC and bone marrow CD34+ cells coincubation of VAA-I with other haematopoietic growth factors induced a dose-dependent increase in clonogenic growth. In cancer patients the mechanisms of natural immunity, believed to be essential for their survival, are often significantly decreased. VAA-I and standardized mistletoe extracts are able to stimulate the cellular parameters of natural immunity with a bell-shaped curve of efficacy. Studies in animal models suggest that application of 0.5-3 ng/kg VAA-I twice a week is effective in sustaining the elevation of the number and activity of peripheral blood NK cells. These parameters often exhibit high intrinsic fluctuations, in healthy persons, however, blind crossover studies reveal an optimal lectin dose of about 0.5 and 1 ng/kg bw, suggesting a potential use of mistletoe preparations as a modulator of the natural immune system. Selective apoptotic effects of VAA-I may represent a novel approach for pharmacological manipulation of the balance between cell growth and programmed cell death. Appropriate combination of immunomodulatory and cytotoxic doses may open new clinical perspectives in the mistletoe therapy.

Bone Marrow Cells↗
PubMed1999

[Cannabis and marijuana as multidrug mixture in phytotherapy].

Without doubt, Cannabis sativa L. is one of the oldest and best-known medical plants. Many traditional and modern ways of use potentially give hints for advantages and risks of different preparations. Several individual experiences of patients and physicians as well as some studies suggest that single substances extracted of or derived from cannabis are not the only useful way for the development of drugs. In comparison to single substances, multidrug mixtures prepared from Cannabis sativa, i. e. classical phytotherapeutics, can show a satisfying and possibly advantageous spectrum of desired but also of unwanted effects.

Cannabis↗
PubMed1999

Comparative study on the in vitro antibacterial activity of Australian tea tree oil, cajuput oil, niaouli oil, manuka oil, kanuka oil, and eucalyptus oil.

To compare the antibacterial activity of the Australian tea tree oil (TTO) with various other medicinally and commercially important essential myrtaceous oils (cajuput oil, niaouli oil, kanuka oil, manuka oil, and eucalyptus oil) the essential oils were first analysed by GC-MS and then tested against various bacteria using a broth microdilution method. The highest activity was obtained by TTO, with MIC values of 0.25% for Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella choleraesuis, Shigella flexneri, Bacillus subtilis, Listeria monocytogenes, Staphylococcus aureus, S. saprophyticus, and S. xylosus. It is noteworthy that manuka oil exhibited a higher activity than TTO against gram-positive bacteria, with MIC values of 0.12%. Both TTO and manuka oil also demonstrated a very good antimicrobial efficacy against various antibiotic-resistant Staphylococcus species. Pseudomonas aeruginosa was resistant to all essential oils tested, even at the highest concentration of 4%.

Anti-Bacterial Agents↗
PubMed1998

Intratumoral injection of encapsulated cells producing an oxazaphosphorine activating cytochrome P450 for targeted chemotherapy.

The prognosis of pancreatic adenocarcinoma is poor and current treatment is for the most part ineffective. We describe here a novel treatment strategy using a mouse model system for pancreatic cancer. Human embryonic epithelial cells have been genetically modified to express the cytochrome P450 2B1 enzyme under the control of a CMV immediate-early promoter. This CYP2B1 gene converts oxazaphosphorines (ifosfamide or cyclophosphamide) to their active cytotoxic compounds, phosphoramide mustard, which alkylates DNA, and acrolein, which alkylates proteins. A number of assays were performed to demonstrate the CYP2B1 gene function as well as toxic effects on neighbouring cells (bystander effect). The cells were then encapsulated in a cellulose sulphate formulation shown to be well tolerated in the pancreas of immunocompetent mice, and injected 1 cm away from pre-established tumours derived from a human pancreatic tumour cell line (PaCa-44). Intraperitoneal administration of low-dose ifosfamide to tumour bearing mice that received the encapsulated cells results in partial or even complete tumour ablation. Such an in situ chemotherapy strategy utilizing genetically modified cells in an immunoprotected environment may prove useful for solid tumour therapy in man.

Adenocarcinoma↗
PubMed1998

Systemic long-term delivery of antibodies in immunocompetent animals using cellulose sulphate capsules containing antibody-producing cells.

Implantation of capsules containing antibody-producing cells into patients would potentially permit systemic long-term delivery of antibodies and might, thus, be useful in the development of surveillance treatments for cancers and severe viral diseases. We show that cellulose sulphate (CS) capsules containing hybridoma cells, when implanted subcutaneously or in the intraperitoneal cavity, can be used for delivering monoclonal antibodies into the blood-stream of immunocompetent mice for at least several months. In contrast to capsules implanted into the intraperitoneal cavity, which remain mobile and nonvascularized, capsules implanted under the skin form neo-organs which become vascularized within days. This may explain the higher blood concentration of the antibody we have observed in the latter case. Importantly, neither an isolating fibrosis nor an obvious inflammatory response was detected at the capsule implantation sites during observation periods as long as 10 months. Finally, no anti-idiotypic immune response against the ectopically delivered antibody was shown to occur. This rules out any potent adjuvant effect of the cellulose sulphate matrix that might have stimulated a neutralizing humoral response. Taken together, our data indicate that encapsulation of antibody-producing cells into CS might be used in antibody-based gene/cell therapy approaches.

Animals↗
PubMed1998

Lectin-induced increase in clonogenic growth of haematopoietic progenitor cells.

The galactoside-specific plant lectin, Viscum album agglutinin (VAA-I) increases cellular parameters of natural host defence. It also binds to a variety of haematopoietic cells, including progenitors. We investigated whether VAA-I has a stimulatory effect on haematopoietic progenitor cells. Peripheral blood progenitor cells from 7 healthy volunteers were cultured in a colony assay with VAA-I plus erythropoietin (EPO) and stem cell factor (SCF). At 50 pg/ml VAA-I induced a significant increase in the cytokine-dependent clonogenic growth (52% in median, p < 0.05). In another set of experiments purified CD34+ cells were isolated from the bone marrow aspirate of 4 patients with non-metastatic breast cancer using fluorescence-activated cell sorting. Binding to CD34+ cells was demonstrated by using directly fluorescence-conjugated VAA-I. Co-incubation with D-galactose significantly abrogated this effect. CD34+ cells were cultured in the presence of EPO, SCF, interleukin-3, granulocyte/monocyte colony-stimulating factor and granulocyte colony-stimulating factor. VAA-I alone had no measurable effect on the clonogenic growth of the isolated cells. However, at concentrations of 100 and 250 pg/ml VAA-I increased the cytokine-dependent proliferation and differentiation of CD34+ cells by a median of 75 and 85%, respectively. The results show that VAA-I binds to haematopoietic progenitor cells and has a co-stimulatory effect on their proliferation.

Antigens, CD34↗
PubMed1998

Effect of a recombinant lectin, Viscum album agglutinin on the secretion of interleukin-12 in cultured human peripheral blood mononuclear cells and on NK-cell-mediated cytotoxicity of rat splenocytes in vitro and in vivo.

A plant lectin, Viscum album agglutinin-I (VAA-I) has been shown to increase the number and cytotoxic activity of natural killer (NK) cells in animal models, but the mechanisms underlying these effects are poorly understood. We investigated the effects of the recombinant form of this lectin (rVAA) on secretion of interleukin (IL)-12 and on NK-mediated cytotoxicity against K562 target cells in cultures of human peripheral blood mononuclear cells (PBMC) as well as against YAC-1 target cells in cultured rat spleen cells. In 24-hour cultures of PBMC, 10 ng/ml plant VAA-I and 50 ng/ml rVAA induced significant increases in the secretion of total IL-12. Its biologically active heterodimeric form, p70, was also significantly induced by rVAA. Preincubation of PBMC or splenocytes for 48 h with rVAA in concentrations ranging between 10 pg/ml and 100 pg/ml resulted in moderate enhancements of NK-mediated cytotoxicity. However, coincubation of a low dose of rVAA (100 pg/ml) together with IL-2 and IL-12 (60 U/ml and 2 U/ml, respectively) led to additive stimulation of NK activity. In in vivo experiments, rVAA showed an enhancing effect on NK activity with a bell-shaped curve of efficacy. Forty-eight hours after a single intravenous injection of its most effective doses, 0.5 and 1 ng/kg, into Wistar rats, the NK cytotoxicity of splenocytes against YAC-1 targets doubled, and the frequency of large granular lymphocytes in peripheral blood showed 2.1- and 3-fold increases as compared to control animals. Twenty-four hours following these low lectin doses, the number of large granular lymphocytes was also significantly elevated. After 48 h, 0.5 ng/kg rVAA induced a significant augmentation in the percentage of peripheral Mac-1+ mononuclear cells, including activated monocytes and NK cells. The present results suggest that rVAA augments the secretion of an active form of IL-12 and potentiates the cytokine-induced NK activation. These effects of rVAA may be related to its stimulatory effects on MHC-unrestricted cytotoxicity in vivo.

Adjuvants, Immunologic↗
PubMed1997

Immunomodulatory effects of Viscum album agglutinin-I on natural immunity.

In 24 h cultured human peripheral blood mononuclear cells, treated with various (1 microgram/ml to 1 ng/ml) concentrations of Viscum album agglutinin-I, quantitative assessment of DNA breaks labelled with terminal deoxynucleotidyl transferase revealed a dose-dependent Viscum album agglutinin-I-induced apoptosis above a lectin concentration of 10 ng/ml. After 24 h incubation of peripheral blood mononuclear cells with non-cytotoxic concentrations of Viscum album agglutinin-I (10 and 1 ng/ml), messenger (m)RNA expression and secretion of a panel of cytokines were evaluated by reverse polymerase chain reaction and by enzyme-linked immunosorbent assay (ELISA), respectively. The lectin induced expression of interleukin-1 alpha, interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, interferon-gamma, granulocyte-monocyte colony stimulating factor and interleukin-10 genes, but no expression of interleukin-2 or interferon-gamma production could be detected. In addition, cellular components of the natural immune system (such as monocytes and granulocytes) bound Viscum album agglutinin-I molecules to a higher degree than lymphocytes. To establish the modulatory potency of Viscum album agglutinin-I on the natural immunity of human subjects, four randomized, double-blind crossover trials were performed on healthy volunteers. In contrast to the significant lectin-induced increases in number and activity of natural killer cells observed in animal models, in the first and second trial human healthy individuals showed no significant differences between their natural killer responses following an injection of lectin-enriched preparation or saline. Due to considerable intrinsic fluctuation of these parameters, a third and fourth double-blind trial with freshly isolated Viscum album agglutinin-I was performed using a more rapidly detectable parameter, the priming of granulocytes. Here, significant lectin-induced increases were found.

Agglutinins↗
PubMed1997

[Foot reflex zone massage--a review].

Reflexology is a frequently used method of complementary medicine. This review deals with history, theory and practise of this technique. Furthermore, results of the published clinical trials are discussed. Although there are more positive than negative results in the therapeutic studies, a final assessment is not possible because of methodological flaws of the studies. More controlled clinical trials are essential.

Chronic Disease↗
PubMed1996

[Use of complimentary medical therapies in HIV/AIDS in Switzerland].

The aim of the present survey was to evaluate the incidence and spectrum of complementary therapies among HIV-infected persons in Switzerland. Under the auspices of the SATG (Swiss Aids Treatment Group), a 13-page questionnaire was created to gather data on socio-demographics, stage of HIV infection, current regimes on opportunistic infections and antiretroviral medication, current and past use of complementary treatments, and reasons for choosing and terminating complementary therapies. Approximately 640 questionnaires in French and German were distributed among HIV-infected subjects. Distributing organizations were People with Aids (P.W.A.), the University Hospital Zurich and the regional "Aids-Hilfe" institutions. With 129 questionnaires returned, the feedback was about 20%. More than 80% of participants used at least one complementary therapy. Each person currently used four therapies (median) from a spectrum of more than 60 specific complementary treatments. The following treatments were used by more than 25% of respondents: vitamins, special diets, food supplements, physical exercise, meditation, phytotherapy, homeopathy, and psychotherapy. 47% of participants took either antiretroviral medication, prophylaxis against opportunistic infections, or both.

Acquired Immunodeficiency Syndrome↗