Biomedical subjects

U Pfüller

Publications and source records attributed to U Pfüller.

At least 37 records · Page 2Linked to original sources

PubMed1999

[Concentrating on weaknesses or compensating by strengths? Comparison of 2 strategies for remediation of children with comprehensive reading-spelling disorder].

Our study compares the efficiency and acceptance of two different methods of treating dyslexia in children. The first method addresses the most commonly encountered deficits in sequential processing. It relies primarly upon the "Kieler Lese-Rechtschreibaufbau". The second proceeds from the child's relative resources with regard to simultaneous processing as described by Kaufman. Training materials are those prescribed by Kaufman. Normally gifted primary school third-graders were trained in two groups (n = 13 and n = 12) and achieved a mean SIF score of SW = 101 on the K-ABC. As expected, the children scored significantly lower on the SED scale (SW = 95) than on the SGD scale (SW = 105). At the beginning of the respective training program their spelling ability fell 1.5 SD below the class mean. One year of regular weekly one-hour training according to the simultaneous processing method was significantly more successful than training in sequential processing, whereas girls improved significantly more than boys regardless of the method used. Acceptance of the methods did not vary. This result requires careful consideration and should be replicated in younger samples such as first- and second-graders in the early stages of learning to read and write, and/or in children whose dyslexia is more severe than that encountered in the current sample. It underscores that determination of an adequate method of remediation entails more than the mere identification of the underlying deficits.

Child↗

PubMed1999

Accidental cell death and generation of reactive oxygen intermediates in human lymphocytes induced by thionins from Viscum album L.

The cytotoxic mechanisms of thionins from Viscum album L., the viscotoxins, were investigated in human granulocytes and lymphocytes. The time course of viscotoxin effects indicate accidental cell death, i.e. membrane permeabilization, degradation of cytoplasm and chromatin, swelling of mitochondria with loss of their cristae, and generation of reactive oxygen intermediates within 1-2 h, followed by secondary apoptosis-associated events. The viscotoxin homologue purothionin from whole-wheat flour and viscotoxin B, however, did not induce cell death in cultured lymphocytes. Cytotoxicity of cationic and amphipathic viscotoxin was prevented only by cleavage of its disulphide bridges.

Apoptosis↗

PubMed1998

Induction of apoptosis by the N-acetyl-galactosamine-specific toxic lectin from Viscum album L. is associated with a decrease of nuclear p53 and Bcl-2 proteins and induction of telomeric associations.

The ribosome-inhibiting proteins from Viscum album L., i.e. the mistletoe lectins (ML), were recognized to induce apoptosis in various tumour cell lines and human lymphocytes. However, several aspects of ML-induced cell death are unclear. We report that the galNAc-binding ML III incubated with human lymphocytes mediates a very effective death signal resulting in the binding of Annexin-V and expression of mitochondrial membrane proteins Apo2.7, but also in an influx of the DNA intercalating dye propidium iodide. The addition of the ribosome-inhibiting protein Volkensin also induced Apo2.7 molecules, while Momordin, lacking a carbohydrate-binding chain, did not enter the cell membrane and thus did not affect the cells. However, we observed ML III to preferentially affect CD8+ cells with a memory phenotype (CD62L(lo)) as compared to their CD8+ CD62L(hi) counterparts, CD4+ T cells and CD19+ B cells. Furthermore, ML III did not induce sister chromatid exchange-inducing DNA lesions but reduced the intensity of telomeric signals, increased the frequencies of telomeric associations and C-anaphases and reduced nuclear Bcl-2 and p53 proteins. Whatever the exact mechanisms are, our results provide strong evidence that the ML III-mediated cytotoxicity involves distinct killing pathways, i.e. (1) primary cell death via an induction of apoptosis which may not be dependent on protein and/or RNA synthesis and may not involve p53 and Bcl-2 proteins and (2) a loss of telomeres resulting in chromosomal instability in the surviving cells which is incompatible with life. However, we cannot exclude the possibility that this effect is due to a decrease in nuclear p53 proteins.

Apoptosis↗

PubMed1998

Selective killing of CD8+ cells with a 'memory' phenotype (CD62Llo) by the N-acetyl-D-galactosamine-specific lectin from Viscum album L.

As reported previously by our group, among the toxic proteins from Viscum album L. only the mistletoe lectins (MLs) induce the apoptotic killing pathway in human lymphocytes. Although one may expect a homogenous distribution of carbohydrate domains on cell surface receptors for the carbohydrate binding B chains of the toxic protein, the sensitivity of cells to these B chains obviously differ. Here we report a selective killing of CD8+ CD62Llo cells from healthy individuals by the galNAc-specific ML III (and RCA60, which binds to gal and galNAc), while the gal-specific ML I was less effective. This selective killing is not sufficiently explained by protein synthesis inhibition alone, since this subset was not affected by other ribosome inhibiting proteins such as the lectin from Ricinus communis (RCA120), lectin from Abrus precatorus (APA), abrin A, and inhibitors of RNA, DNA and/or protein synthesis such as actinomycin D, mitomycin C, and cycloheximide. We conclude that CD8+ cells with 'memory' phenotype (CD62Llo) are more sensitive to the ML III-mediated killing than their CD8+ CD62Lhi counterparts, CD4+ T cells, and CD19+ B cells. These cells probably express a distinct receptor with galNAc domains that is missing or not active on CD8+ cells with a 'naive' phenotype.

Acetylgalactosamine↗

PubMed1998

[Effects and significance of specific spelling problems in young adults--empirical studies in an epidemiologic patient sample].

OBJECTIVE: With reference to an epidemiological sample of adolescents and young adults the impact of different models on the number of children classified as having specific spelling problems is investigated. METHOD: Using the same set of data, the effect of alternative definitions and methodological procedures on the prevalence of specific spelling retardation is shown. The virtual consequences of various norm-orientated definitions of cases is discussed with reference to external empirical criteria. RESULTS: Particularly, obsolete norms lead to a large overestimation of cases. In the present study case definitions of specific spelling retardation based on substantial criteria result in prevalence rates between 6 and 9 percent. Academic achievement is considerably affected by persisting specific spelling problems and the attendance of secondary schools is rare, in spite of sufficient nonverbal intelligence. CONCLUSIONS: Because of the high impact of spelling ability for educational success, dyslexic children need help by early intervention. Furthermore scholastic promotion is necessary to enable a school carer appropriate to the intellectual possibilities of the child.

Achievement↗

PubMed1996

Isolation and partial characterization of a small chitin-binding lectin from mistletoe (Viscum album).

A novel lectin, called VisalbCBA, was isolated from European mistletoe (Viscum album). This lectin differs completely from the classical galactose/N-acetylgalactosamine-binding mistletoe lectins MLI, MLII and MLIII. Biochemical analyses indicated that VisalbCBA is a dimeric protein composed of two identical subunits of approx. 10 kDa. VisalbCBA exhibits specificity towards oligomers of N-acetylglucosamine and shows sequence homology to the previously isolated chitin-binding plant proteins. Although VisalbCBA is less toxic than the other mistletoe lectins, it definitely exhibits cytotoxic properties. The possible involvement of VisalbCBA in the biological and therapeutic effects of mistletoe is discussed.

Amino Acid Sequence↗

PubMed1996

Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins.

Viscum album L. (VAL) is a phytopreparation used in adjuvant cancer therapy with both immunostimulatory and DNA stabilizing properties at low drug concentrations and cytostatic/cytotoxic properties at higher concentrations. The present work examines the cytotoxic effects of VAL extracts produced from mistletoes grown on different host trees and of purified toxic proteins from VAL, such as the D-galactose-specific lectin I (ML I), the N-acetyl-D-galactosamine-specific ML II and ML III, and crude viscotoxins towards cultured human lymphocytes. The decrease in the number of cultured lymphocytes and blast cells treated with whole plant extracts from VAL was host tree-specific. Nevertheless, there was no close correlation to the content of MLs or viscotoxins. Using the purified proteins, it became obvious that the cell killing was mediated by the induction of apoptosis, as measured by the appearance of a hypodiploid DNA peak using flow cytometry. ML III was the most effective to induce apoptosis, followed by ML II and ML I, while the viscotoxins and oligosaccharides from VAL did not. By measuring the surface expression of IL-2R alpha chains, transferrin receptors and APO-1/Fas molecules on non-apoptotic T cells, no significant changes were observed at low ML concentrations (1 ng/ml), but their decrease at higher ones. Our findings suggest that there might be at least two different ways of cell killing operative in VAL-mediated cytotoxicity: (a) the typical apoptotic cell death with the appearance of hypo-diploid nuclei, and (b) a direct or indirect killing by damaging the cell membrane with subsequent influx of Ca2+ and of the DNA intercalating dye propidium iodide and cell shrinkage. These effects might not be exclusive, as they probably occur simultaneously.

Apoptosis↗

PubMed1996

Stimulation of cytokine production via a special standardized mistletoe preparation in an in vitro human skin bioassay.

The mistletoe preparation Lektinol is standardized with respect to bioactive mistletoe lectin, the active component of mistletoe. This standardized mistletoe preparation and its active components (mistletoe lectins) were compared in the skin2 bioassay in vitro for their capacity to stimulate interleukin 1 alpha and interleukin 6 release from skin analogue tissue, composed of human cells in their naturally secreted matrix. The standardized mistletoe preparation, its basic ingredient, aqueous mistletoe extract, and pure mistletoe lectins all stimulated IL-1 alpha and IL-6 release from skin2 tissues during 24 h incubation. The amounts of cytokines released from various skin2 tissue lots by mistletoe lectin I (ML I) (0.75-8.0 ng/ml) and by the standardized mistletoe preparation remained relatively constant across a series of different batches. Concentration-response curves to the standardized mistletoe preparation and ML I were similar for IL-1 alpha and IL-6 release. The importance of the concentration of mistletoe lectins for the cytokine-releasing action of the standardized mistletoe preparation was confirmed using a neutralizing anti-mistletoe lectin antiserum. CONCLUSIONS. Using the skin2 method it was shown that reproducible stimulation of cytokine release by a standardized mistletoe preparation from batch to batch is one of the notable features of its pharmaceutical quality. This standardized mistletoe preparation therefore represents a preparation with constant immunobiological effects. Mistletoe lectins of the standardized mistletoe preparation are the active substances in the skin2 bioassay. The skin2 method is a reliable quantitative bioassay for determination of immunopharmacological effects.

Biological Assay↗

PubMed1996

[Handedness and cognitive abilities: findings in a representative sample of adolescents and young adults].

Handedness and cognitive abilities in a representative sample of adolescents and young adults. The relationship between laterality and cognitive ability was examined in a representative sample of adolescents and young adults between 16 and 30 years of age. The study was designed as a possible replication of Annett's data supporting her right-shift theory (rst), but included other measures of laterality as well. We found, as Annett did, that strong right-handedness was associated with a weak left hand rather than a strong right hand. However, we could not confirm two other predictions of the rst with our data: The nonverbal IQ was significantly lower in both extreme groups of handedness than in the two middle groups. Because of the sample size this rather small effect, explaining only 1.9% of the variance, is significant, but it disappears with other kinds of grouping for handedness. We could not find the linear decline in nonverbal IQ from the left to the right extreme of handedness as predicted by the rst. In spelling, too, there was a rather small, but significant effect of handedness, explaining 2.4% of the variance. Spelling in the first (left most) quartile of handedness was worse than in quartiles two and four. The predicted poorer spelling in the extreme groups than in the middle groups (inverted U) was not found in our sample. In multivariate analysis with variables explaining larger proportions of the variance in spelling (education, nonverbal IQ and sex) the small effect of handedness on spelling completely disappeared. A weak relationship between left-handedness and dyslexia was evident only with the strictest definition of dyslexia, regardless of how handedness was defined. The implications of these data for the rst are discussed.

Adolescent↗

PubMed1995

Interaction of mistletoe toxic lectin-I with sialoglycoproteins.

The binding properties of mistletoe toxic lectin-I (ML-I) with sialo-N- and O-glycans were investigated by quantitative precipitin and precipitin inhibition assays. Human alpha 1-acid glycoprotein reacted strongly with ML-I, precipitating over 82% of the lectin nitrogen tested, while the precipitability of its asialo product decreased by 30%. Native fetuin precipitated 50% of the ML-I added, and its reactivity was reduced by 20% after desialylation. On the contrary, the poor reactivity of rat sublingual sialoglycoprotein with ML-I increased substantially after removal of sialic acid and completely precipitated the lectin added. The glycoprotein-lectin interactions were inhibited by NeuAc alpha 2-->3/alpha 2-->6Gal beta 1-->4Glc and/or Gal beta 1-->4Glc (NAc) residues. From the above results, it is concluded that ML-I is specific for sialic acid. However, sialic acid of some O-glycans also acts as masking molecule as the precipitability of rat sublingual and bovine submandibular glycoproteins with ML-I increased after desialylation.

Animals↗

PubMed1995

A sheep hydatid cyst glycoprotein as receptors for three toxic lectins, as well as Abrus precatorius and Ricinus communis agglutinins.

The binding properties of a glycoprotein with blood group P1 specificity isolated from sheep hydatid cyst fluid with Gal and GalNAc specific lectins was investigated by quantitative precipitin and precipitin inhibition assays. The glycoprotein completely precipitated Ricinus communis agglutinin (RCA1), Abrus precatorius agglutinin (APA) and Mistletoe toxic lectin-I (ML-I). Only 1.0 microgram of P1 glycoprotein was required to precipitate 50% of 5.1 micrograms ML-I nitrogen. It also reacted well with abrin-a and ricin, precipitating over 73% of the lectin nitrogen added, but poorly or weakly with Dolichos biflorus (DBL), Vicia villosa (VVL, a mixture of A4, A2B2 and B4), VVL-B4, Arachis hypogaea (PNA), Maclura pomifera (MPL), Bauchinia purpurea alba (BPL) and Wistaria floribunda (WFL) lectins. When an inhibition assay in the range of 5.1 micrograms N to 5.9 micrograms N of lectins (ML-I, abrin-a; ricin, RCA1, and APA, and 10 micrograms P1 active glycoprotein interaction was performed; from 76 to 100% of the precipitations were inhibited by 0.44 and 0.52 mumol of Gal alpha 1-->4Gal and Gal beta 1-->4GlcNAc, respectively, but not or insignificantly with 1.72 mumol of GlcNAc. The Gal alpha 1-->4Gal disaccharide found in this P1 active glycoprotein is a frequently occurring sequence of many glycosphingolipids located at the surface of mammalian cell membranes, especially human erythrocytes and intestinal cells for ligand binding and microbial toxin attachment. The present finding suggests that the Gal alpha 1-->4Gal beta 1-->4GlcNAc sequence in this P1 active glycoprotein is one of the best glycoprotein receptors for three toxic lectins (ricin, abrin-a, and ML-I) as well as for APA, and RCA1, and the result of inhibition assay implies that these lectins are recognizing part or all of the Gal alpha 1-->4Gal beta 1-->4GlcNAc sequence in the P1 active glycoprotein.

Animals↗

PubMed1995

Biochemical, histochemical and cell biological investigations on the actions of mistletoe lectins I, II and III with human breast cancer cell lines.

Cytotoxicity of the mistletoe lectins I, II and III towards six human breast cancer cell lines was assessed using the Mossman assay. In addition, binding of the three mistletoe lectins to the separated membrane glycoproteins of these cell lines, the binding and uptake of these lectins into the cells in tissue culture and the binding of the lectins to histological preparations of these cell lines were analysed. The results indicate that there are quantitative differences concerning the toxicity of these three lectins towards the different cell lines. Furthermore, the lectin binding pattern in the cell lines differed. In Western blots, several membrane glycoproteins were labelled by the lectins. Our results indicate subtle differences between the three lectins with regard to the parameters mentioned above; however, the toxicity of all three lectins from mistletoe is so similar that they all seem suitable for the construction of immunotoxins.

Breast Neoplasms↗

PubMed1994

Staining of cerebral amyloid plaque glycoproteins in patients with Alzheimer's disease with the microglia-specific lectin from mistletoe.

Glycoconjugates in the amyloid plaques in the cerebral cortex of patients with Alzheimer's disease were stained with a lectin from mistletoe (ML-I). This lectin selectively stains microglial cells which can be found in the centre of many plaques. Since the terminal carbohydrate moieties of some but not all of the plaques, which mainly consist of beta A4 protein, are identical to those of the microglial cells it is concluded that glycoproteins within these plaques have been synthesised by the microglial cell. These microglia deposited glycoproteins may be of importance for the formation of mature amyloid plaques.

Alzheimer Disease↗

PubMed1994

Binding patterns of mistletoe lectins I, II and III to microglia and Alzheimer plaque glycoproteins in human brains.

Glycoconjugates of microglial cells and in some cases those glycoconjugates present in the amyloid plaques in Alzheimer's disease in the cerebral cortex can be stained with a lectin from mistletoe (ML-I) using a labour-intensive and time-consuming indirect immunoperoxidase technique. In order to simplify the staining method and to test the staining characteristics of the other recently isolated mistletoe lectins (ML-II, ML-III) biotinylated MLs I-III were used together with an avidin-alkaline phosphatase-complex for visualisation. Our findings indicate that this new improved technique can also be used for detection of microglial cells and is considerably faster than the old method. In addition to microglial cells, ML-I labelled plaque glycoproteins possibly indicating that glycoconjugates derived from microglia can be detected in plaques. In contrast to ML-I, both ML-II and ML-III did not stain microglial cells.

Alzheimer Disease↗

PubMed1994

Is the binding of mistletoe lectins I and III a useful prognostic indicator in colorectal carcinoma?

A retrospective study on 127 patients with colorectal carcinoma was performed to evaluate the use of mistletoe lectins I and III as possible prognostic indicators. Tissue sections were stained by a histochemical technique using these lectins and the staining results correlated with survival. No correlation between survival and the presence of lectin binding or non-binding was found. A lectin with the same monosaccharide specificity as ML-III, Helix pomatia agglutinin, which was of prognostic significance in the same patient cohort in another study showed on Western blot analysis a slightly different lectin binding pattern towards glycoproteins than the MLs. The results of this study indicate that even subtle differences in the carbohydrate composition of glycoconjugates which can be differentiated by lectins are of biological significance in terms of the metastatic spread of tumours.

Blotting, Western↗

PubMed1993

Crystallization of the ribosome inactivating protein ML1 from Viscum album (mistletoe) complexed with beta-D-galactose.

A ribosome inactivating protein (ML1) from the mistletoe plant (Viscum album) has been crystallized. The crystals, grown in the presence of beta-D-galactose, are hexagonal, space group P6(1)22 or P6(5)22, a = b = 111.0 A, c = 309.3 A with 24 molecules per unit cell (assuming 33% solvent by weight). The protein of molecular mass 63 kDa is a heterodimer consisting of two chains, A and B, joined by a disulfide bond. The A-chain, 29 kDa, inhibits protein synthesis by depurinating an adenine residue (A4324) in a highly conserved RNA loop of the 28 S ribosomal subunit. The toxicity of the protein is mediated by the B-chain, 34 kDa, which has lectin activity, interacting with sugar residues of glycoproteins and glycolipids on the surface of target cells.

Crystallography, X-Ray↗

PubMed1992

Carbohydrate specificity of the receptor sites of mistletoe toxic lectin-I.

The carbohydrate specificity of mistletoe toxic lectin-I (ML-I) was studied by haemagglutination-inhibition assay. The results indicated that ML-I has a broad range of affinity for Gal alpha,beta linked sequences. The galabiose (E, Gal alpha 1----4Gal) sequence, a receptor of the uropathogenic E. coli ligand, was one of the best disaccharide inhibitors tested. The lectin also exhibits affinity for Lac(Gal beta 1----4Glc), T(Gal beta 1----3GalNAc), I/II(Gal beta 1----3/4GlcNAc) and B(Gal alpha 1----3Gal) sequences. Gal alpha 1----4Gal and Gal beta 1----4Glc are frequently occurring sequences of many glycosphingolipids located at the mammalian cell membranes, such as intestinal and red blood cell membranes, for ligand binding and toxin attachment. This finding provides important information concerning the possible mechanism of intoxication of cells by the mistletoe preparation.

Binding Sites↗

PubMed1990

The effect of amphiphilic polymers on growth of Bordetella pertussis and production of B. pertussis haemagglutinins.

The effect, upon addition to a culture medium of amphiphilic polymers such as partly hydrolysed polyvinyl acetate (PVAc) or partly methylated cellulose (MeCel) on growth and production of haemagglutinins--the filamentous haemagglutinin (FHA) and the pertussis toxin (PT)--has been investigated. As a result, an increase of HA-titer and PT could be achieved. Besides these effects the addition of the amphiphilic polymers stimulated growth of B. pertussis. The above results are comparable to, or even better than, those obtained by addition of Heptakis (2,6-0-dimethyl) beta-cyclodextrin (Me-beta-CD) or polyvinyul alcohols (PVA) which have already been described as compounds to enhance growth and yield of haemagglutinins.

Adhesins, Bacterial↗