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Biomedical subjects

G M Stein

Publications and source records attributed to G M Stein.

At least 37 records · Page 2Linked to original sources

Evaluation of the stimulatory activity of a fermented mistletoe lectin-1 free mistletoe extract on T-helper cells and monocytes in healthy individuals in vitro.

Previously, a strong stimulatory response of peripheral blood mononuclear cells (PBMC) to a fermented mistletoe extract (Iscador Pini, i.p.) could be observed in normal and allergic individuals. Aim of this study was therefore to analyse the cell subtypes involved in this in vitro reactivity. PBMC from 11 non-mistletoe treated healthy and allergic individuals were therefore investigated. Flow cytometric analyses revealed that this mistletoe extract stimulated T-cells (CD3+), especially T-helper cells (CD4+), as well as monocytes at concentrations of 100 or 1,000 micrograms/ml. Furthermore, an increased proportion of T- and T-helper cells expressing the interleukin-2 (IL-2) receptor (CD25) and monocytes expressing HLA-DR molecules, respectively, could be demonstrated. There was no evidence for a major involvement of B- (CD19+), natural killer- (NK-; CD56+) and T-suppressor cells/cytotoxic T-lymphocytes (CD8+). To get more insights whether the T-cell proliferation induced by i.p. was the consequence of a primary or a secondary type of immune response, kinetic studies (n = 5) were performed hereby comparing the reactivity of the non-recall antigen keyhole limpet hemocyanin (KLH) as well as the recall antigen purified protein derivative (PPD) derived from Mycobacterium tuberculosis with that of i.p. I.p. at a concentration of 100 micrograms/ml always exhibited the kinetics of a primary immune reaction. These findings were further substantiated by additional flow cytometric studies analysing changes in the proportions of naive (CD45RA+) and memory/effector cells (CD45RO+) during the exposure to i.p. It could be shown that the proportion of naive cells decreased and that of the transition stage increased, which could indicate that there was a change towards memory/effector cells. In conclusion, these data demonstrate that i.p.-related antigens act like "non-recall"-antigens, and the in vitro immune response involves T-cells as well as monocytes.

Adjuvants, Immunologic↗

Encouraging a balanced style of living.

The Personnel Management System, as with any good business plan, assists employees in establishing ways to measure progress or completion of chosen goals.

Hospital Bed Capacity, 100 to 299↗

Lateral eye movement and handedness as measures of functional brain asymmetry in learning disability.

Evidence is presented which suggests that learning disability is related to lateral asymmetry. Significant differences were found in lateral eye movement and handedness between a learning disabled group and a control group of normal learners. Left lateral eye movement and right handedness was the predominant pattern exhibited in learning disability. These results support Day's notion that left lateral eye movement is associated with educational difficulties. They also provide evidence concerning Orton's hypothesis that mixed cerebral dominance characterizes the learning disabled.

Child↗

Does personal future outlook cause self-esteem?

Melges et al. (1971) presented evidence that a client's sense of self-worth is highly correlated with his degree of optimism about his personal future. In the present study, the cross-lagged panel correlation (CLPC) technique was used to test their hypothesis that changes in personal future outlook lead to changes in self-esteem. Ninety-four outpatients in the private psychiatric practice of the senior author filled out the Decision-Making Evaluation Instrument used by Melges et al. to assess these two constructs as well as decision-making and outcome. Results did not support their implication that personal future outlook is causally predominant over self-esteem, nor did the results support their assumption that they were measuring a distinct construct of self-esteem.

Adolescent↗

Thionins from Viscum album L: influence of the viscotoxins on the activation of granulocytes.

BACKGROUND: Extracts from European mistletoe (Viscum album L.) are applied in adjuvant cancer treatment, and some components, especially the mistletoe lectins (ML) have been immunologically characterised, but not the thionins, termed viscotoxins (VT). MATERIALS AND METHODS: The influence of the VT on human granulocytes was studied by flow cytometry: E.coli co-stimulated respiratory burst by oxidation of dihydrorhodamine 123 to rhodamine 123 and phagocytosis by ingestion of FITC-labelled E.coli. RESULTS: VT (25 and 250 micrograms/ml), in contrast to ML, significantly enhanced phagocytosis and burst activity. VT-rich mistletoe extracts also exerted significant effects. In addition, E.coli-activated granulocytes positively stain with Annexin-V and propidium iodide only due to 250 micrograms/ml VT incubation, suggesting that at this concentration burst activity was induced by the physiological activity of granulocytes after microbial ingestion and also by cytotoxic effects. CONCLUSION: Viscotoxins exert yet unknown strong immunomodulatory effects on human granulocytes, which might be of benefit for tumour patients, in addition to their cytotoxic properties.

Adjuvants, Immunologic↗

Induction of Fas ligand (CD95L) by the toxic mistletoe lectins in human lymphocytes.

BACKGROUND: Fas ligand (FasL, CD95L) predominantly expressed on activated cytotoxic T cells and NK cells triggers apoptosis in Fas receptor (Apo-1, CD95) positive target cells. We investigated the expression of FasL, Fas and tumor necrosis factor (TNF) receptor 1 (TNF-R1, CD120a) on cultured human lymphocytes and leukemic T and B cells. MATERIALS AND METHODS: Lymphocytes from six healthy individuals, from four patients with chronic lymphocytic T or B cell leukaemia, and leukemic Molt-4 cells were incubated with the apoptosis- inducing mistletoe lectins (ML I and ML III). RESULTS: Incubation of differentiated lymphocytes with the ML resulted in a significant upregulation of FasL in the surviving CD4+ T helper cells, CD8+ cells and CD19+ B cells. Similarly, the TNF receptor expression increased, while the Fas molecule decreased. In contrast, FasL was not induced in leukemic cells. CONCLUSIONS: Apart from a direct induction of apoptosis in response to an inhibition of protein synthesis by the enzymic ML A chain, ML treatment may indirectly induce apoptosis in Fas+ tumour cells through activated FasL+ lymphocytes.

Antigens, CD↗

Influence of polysaccharides from Viscum album L. on human lymphocytes, monocytes and granulocytes in vitro.

BACKGROUND: An acidic arabinogalactan from European mistletoe (Viscum album L, VAL; 1.34 x 10(6) Dalton) was studied in detail because its immunological properties are poorly characterised. MATERIALS AND METHODS: Flow cytometric studies focussed on PS-activated proliferation of human lymphocytes measured via incorporation of bromo-deoxyuridine (BrdU), granulocyte phagocytosis via ingestion of FITC-labelled E.coli, and respiratory burst via oxidation of dihydrorhodamine 123 to rhodamine 123. Cytokines were detected in the cell culture supernatants by ELISA. RESULTS: PS, in contrast to mistletoe lectins (ML), significantly stimulated proliferation of CD4+ T-cells but not CD8+ and CD19+ cells. However, ML influenced PS-mediated stimulation, with a synergistic effect in one and an inhibitory effect in another individual. Furthermore, IFN-gamma release was significantly enhanced by PS, favouring a T-helper cell type-1 cytokine pattern, further IL-6 was significantly stimulated, while granulocyte activity was not affected. CONCLUSIONS: VAL-PS exert yet unknown stimulatory activities, especially on specific CD4+ T-cells which may be influenced by other extract components like the ML. These components may contribute to the anti-tumour effect of VAL.

Adjuvants, Immunologic↗

Release of interleukin-6 in cultured B-chronic lymphocytic leukaemia cells is associated with both activation and cell death via apoptosis.

BACKGROUND: There is growing evidence that some cytokines promote B cell survival, while others enhance cell death. Interleukin-6 was reported to induce proliferation of chronic lymphocytic leukaemia (B-CLL) cells, and to enhance survival of these cells through inhibition of spontaneous apoptosis. MATERIALS AND METHODS: To more clearly define the effects of an in vitro stimulation of B-CLL cells, lymphocytes from 13 patients with B-CLL and from 6 healthy individuals were incubated for 7 d with immunomodulators such as interleukin-6 (IL-6), pokeweed mitogen (PWM), lipopolysaccharides (LPS), and extracts from Viscum album L. (VAL; Helixor), which were recognised to induce apoptosis but also to induce a release of pro-inflammatory cytokines such as IL-1, IL-6, and tumour necrosis factor-alpha. RESULTS: Although both, IL-6 and PWM induced a release of IL-6 and expression of the activation markers CD25 and CD71 on the surface of B-CLL cells, IL-6 did not increase or accelerate the proliferation of these cells. In contrast, VAL extracts did not result in an upregulation of activation markers or proliferation of B-CLL cells but induced both, cell death via apoptosis and IL-6 release. In response to PWM, only few clones of leukemic B cells incorporated the thymidine-analogue 5-bromo-2'-deoxyuridine. Moreover, a remarkable response of B-CLL cells towards the immunomodulators was observed only in one patient with an advanced stage. CONCLUSIONS: These preliminary results do not support theoretical objections of a B-CLL stimulation via induction of IL-6 in vitro.

Aged↗

Viscotoxin-free aqueous extracts from European mistletoe (Viscum album L.) stimulate activity of human granulocytes.

BACKGROUND: Extracts from European mistletoe (Viscum album L., VAL) are used for complementary cancer treatment. Viscotoxins (VT) and whole plant extracts with high amounts of the VT have been shown to stimulate functional activity of granulocytes. MATERIALS AND METHODS: We stimulated neutrophils from healthy donors in vitro with aqueous VT-free VAL extracts and mistletoe lectins (ML) in the presence of E.coli and studied phagocytosis (via incorporation of FITC-labelled E.coli) and respiratory burst (via oxidation of dihydrorhodamine 123 to rhodamine 123) by flow cytometry. RESULTS: The VT-free VAL extract significantly stimulated granulocyte activity, and this effect correlated with the content of the ML, although the ML exerted no influence at relevant concentrations. Co-incubation of the cells with VAL in the presence of VT further increased granulocyte response. CONCLUSIONS: From these data it is suggested that (1) a non-VT non-ML component of the VAL extracts activated granulocytes and (2) different activation pathways may be involved in the stimulation by the whole plant extract and the VT.

Granulocytes↗

Differential binding of toxic lectins from Viscum album L., ML I and ML III, to human lymphocytes.

The killing capacity of extracts from Viscum album L., widely used as an adjuvant in complementary cancer therapy, is dependent on the content of toxic proteins, especially the mistletoe lectins (ML). Although one may expect a homogeneous distribution of 'receptors' for these proteins on the cell surface, the sensitivity of cells to the ML-mediated cytotoxicity obviously differs, as the galNAc-binding ML III in contrast to the gal-binding ML I selectively killed CD8+ lymphocytes with a 'memory' phenotype (CD62Llo), while CD19+ B cells remained almost unaffected. B cells hardly bind ML III but did bind the gal-specific ML I. In accordance with these observations, in leukaemic B cells from patients with B chronic lymphocytic leukaemia and the human IgE-secreting myeloma cell line U-266 a strong induction of apoptosis-associated mitochondrial Apo2.7 molecules was observed after treatment with ML I and less effectively by ML III, while in the leukaemic T cell line Molt-4 both ML were strong inductors of apoptosis. In the light of these findings, the possible impact of ML I- and ML III-rich mistletoe extracts in the treatment of B cell neoplasia has to be carefully investigated.

Apoptosis↗