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Biomedical subjects

A Büssing

Publications and source records attributed to A Büssing.

At least 19 recordsLinked to original sources

The care information system PIK--the fit between user and system.

OBJECTIVES: The presented laboratory study explores the relationship between the care information system PIK and its users, focusing on intuitive program usage, occurring errors, the usefulness of the evaluation method, and the role of person related variables. METHODS: Three studies were conducted. While thinking aloud, a sample of 26 participants performed certain tasks, which were recorded in protocols. In addition, the occurring errors were rated in an error taxonomy. RESULTS: While the actual use of the program proved quite easy, conceptual structuring caused the participants difficulties. These difficulties stemmed mainly from problems encountered in generating a clear mental picture of the system, and the consequences of the actions. Over time, the program showed a positive development. CONCLUSIONS: Discussion of the results focuses on implementation processes in the context of usability research. The need to train users in the conceptual structure of the program and to build realistic expectations are the focus of our outline.

Adult↗

The role of tacit knowledge in the work context of nursing.

AIMS OF THE STUDY: Previous research on the role of tacit knowledge is ambiguous. Some studies show the superiority of expertise, while other studies found experts would not be better than laymen. This paper aims at clarifying the contribution of tacit knowledge to expertise in the domain of nursing. BACKGROUND: Two important concepts for dealing with critical situations are outlined - tacit knowledge and experience-guided working. The framework of tacit knowledge and experience-guided working can contribute to an explanation of the ambiguous results. Tacit knowledge is acquired implicitly in the course of working and is therefore not subject to reflection. For this reason it can contain erroneous or problematic contents. METHODS: A method for the explication of tacit knowledge was developed and a laboratory study with 16 experienced nurses conducted. In the laboratory study the nurses had to deal with a critical nursing situation that was developed in co-operation with nursing experts. The explicit knowledge of the nurses was tested before the laboratory study. RESULTS: No systematic differences in explicit knowledge could be observed, i.e. differences in performance could not be attributed to this knowledge mode. Results from multidimensional scaling procedures illustrate differences in the tacit knowledge of nurses who successfully accomplished the critical situation and those who did not. CONCLUSIONS: The findings are in line with the assumption that experience-guided working is of the utmost importance for dealing with critical situations. Consequences of these results for nursing and person-related services in general are discussed and the aim of future research is outlined.

Adaptation, Psychological↗

Expression of interleukin-4 in apoptotic cells: stimulation of the type-2 cytokine by different toxins in human peripheral blood mononuclear and tumor cells.

BACKGROUND: Immunological reactivity is regulated by T-cell populations (type-1 and type-2 cells) via cytokine secretion, but their influence on apoptosis remains unclear. METHODS: Intracellular expression of type-1 (interferon [IFN]-gamma) and type-2 (interleukin [IL]-4) cytokines and apoptosis-related molecules (Apo2. 7, Bcl-2 protein) was studied by flow cytometry in human peripheral blood mononuclear cells (PBMC), myeloma (U-266), monocytic (THP-1), and T-leukemia cells (MOLT-4) in response to toxins, which act on different intracellular targets (actinomycin D, cycloheximide, the mistletoe lectins [ML]-1 and ML-3, brefeldin A, staurosporine). RESULTS: The apoptosis-inducing toxins stimulated intracellular IL-4 expression mainly in PBMC with high expression of the mitochondrial apoptosis marker, Apo2.7, but with decreased level of the anti-apoptotic Bcl-2 protein. Up-regulation of IL-4 coincided with a significant down-regulation of IFN-gamma in CD4(+) and CD8(+) cells. The inhibitor of oxidative phosphorylation, oligomycin, and the caspase inhibitor, z-VAD-fmk, abolished IL-4 expression and DNA fragmentation in the PBMC. Also in the myeloma, monocytic, and T-leukemia cells, IL-4 was mainly observed in the Apo2.7(+) apoptotic cells in response to the toxins. CONCLUSIONS: We suggest that the different apoptotic toxins activate a common pathway in which IL-4 production plays a yet unknown intracellular role further downstream during apoptosis.

Apoptosis↗

Induction of apoptosis by mistletoe lectin I and its subunits. No evidence for cytotoxic effects caused by isolated A- and B-chains.

Type II ribosome inactivating proteins (RIP II) are generally known to induce apoptosis in human cells by the inhibition of protein biosynthesis. Recent data from mistletoe RIP II proteins (eg. mistletoe lectin I; ML1) suggest an additional mode of apoptosis induction through the binding of their lectin part to certain cell surface receptors as is known for some human galectins. In order to clarify this possibility, we used highly sensitive flow cytometric apoptosis assays and mistletoe hololectin subunits of proven purity to show that neither human lymphocytes nor Molt-4 cells undergo apoptosis after treatment with isolated lectin-type B-chains. In contrast to earlier investigations, only the hololectin was able to induce apoptosis in these assays. We conclude that direct apoptosis induction by mistletoe lectins occurs only after uptake of the molecules into the cell due to the action of the ribosome inactivating A-chain.

Apoptosis↗

[Intuition as implicite knowledge].

The article relates the terms intuition, tacit knowledge and experience and describes their meaning for nursing. An empirical study with 16 experienced nurses is presented whereby the nurses had to deal with a simulated critical nursing situation. Basing on their actions a method for explication of action-guiding tacit knowledge was developed so that a closer scrutinizing of this type of knowledge became possible. Results underline the assumption of many practitioners that intuition as a resource in nursing activities is not to underestimate. At the same time a warning is given: Intuition and tacit knowledge is not always and at all times to evaluate positively. Finally, this differentiated point of view is discussed regarding consequences for nursing practice.

Humans↗

Expression of mitochondrial Apo2.7 molecules and caspase-3 activation in human lymphocytes treated with the ribosome-inhibiting mistletoe lectins and the cell membrane permeabilizing viscotoxins.

BACKGROUND: It is unclear whether expression of newly described mitochondrial Apo2.7 molecules (7A6 antigen) is specific for apoptosis or may also occur in necrosis. METHODS: We incubated human lymphocytes with the apoptosis-inducing mistletoe lectin (ML) I and the cell membrane-permeabilizing viscotoxins (VT), and measured cell death-associated changes by flow cytometry. RESULTS: In ML I-treated lymphocytes, Apo2.7 expression and caspase-3 activation was recognized within 24 h. In VT-treated cells, we observed an Apo2.7 expression with low fluorescence level, while active caspase-3 and DNA fragments (TUNEL) were not detected within 24 h. In these cells, caspase-3 activation was recognized 48 h later. As a major subset of ML-treated cells expressing Apo2.7 molecules did not activated caspase-3, while all caspase-3(+) cells did express Apo2.7, one may suggest that the caspase pathway is activated secondarily to mitochondrial events. CONCLUSIONS: Expression of Apo2.7 is sensitive marker of cell death but may not be specific for apoptosis alone as it can be detected also in cells treated with cell membrane-permeabilizing toxins. On the other hand, this expression may be the consequence of an induction of distinct "death signals" resulting in apoptosis later on.

Apoptosis↗

Induction of mitochondrial Apo2.7 molecules and generation of reactive oxygen-intermediates in cultured lymphocytes by the toxic proteins from Viscum album L.

We analysed mitochondrial alterations in human lymphocytes incubated with toxins exerting RNA and/or protein synthesis/transport inhibitory activity. We found that all toxins known to affect macromolecule synthesis, such as ricin from Ricinus communis, mistletoe lectin I (ML I) from Viscum album, cycloheximide, actinomycin D, and brefeldin A but also the thionins from Viscum album (viscotoxins; VT) generated reactive oxygen intermediates (ROI) and induced expression of newly described mitochondrial membrane proteins Apo2.7, however, with different kinetics. Apart from a rapid permeabilisation of cell membranes by the VT with swelling of mitochondria, loss of their cristae and ROI generation within 2-4 h, the majority of the cells may have received a distinct 'death signal' resulting in an induction of Apo2.7 molecules within 24 h. In contrast, protein synthesis/transport inhibition may signal for apoptosis within 24 h by decreasing distinct 'survival promotors' which remain to be characterised.

Annexin A5↗

Characterisation of granulocyte stimulation by thionins from European mistletoe and from wheat.

Thionins are small basic peptides found in different plant species, which are known to exert cytotoxic properties. In addition, previous data indicated an activation of human granulocytes by thionins from European mistletoe (viscotoxins, VT). To extend these latter findings, we investigated the influence of VT and from thionins from wheat flour (purothionin) on human granulocytes by flow cytometry and tried to characterise the involved molecular structures and mechanisms. Phagocytosis was determined by incorporation of FITC-labelled Escherichia coli and respiratory burst by oxidation of dihydrorhodamine 123 to rhodamine 123. VT and purothionin significantly enhanced E. coli-stimulated phagocytosis and respiratory burst at 25 and 250 microgram/ml. Phagocytosis of damaged lymphocytes by granulocytes was detected by electron microscopy in the VT-stimulated (100 microgram/ml) but not in the control cultures. The poly-cationic structure of the intact molecule seems to be crucial, as evidenced by comparison of the burst and phagocytosis-enhancing effects induced by other poly-cationic (protamine sulphate, histone, poly-l-arginine, poly-l-lysine) and poly-anionic (poly-l-glutamic acid) peptides, while pore forming due to amphipathic properties seems to be less important. Ca2+ and Mg2+ could not inhibit VT-enhanced phagocytosis and, thus, could not inhibit binding of VT to granulocytes. In addition, verapamil at low concentrations inhibited VT activity, suggesting the involvement of Ca2+ channels for granulocyte activation by the VT. Similarly, thionins and histones in contrast to protamine sulphate induced cell death of granulocytes at 250 microgram/ml as demonstrated by an enhanced release of reactive oxygen intermediates in unstimulated granulocytes. From these data one may suggest that activity of VT is induced by strong unspecific ionic binding, probably followed by specific receptor binding, and thionins exhibit stimulatory and cytotoxic effects on immune cells, which have to be further characterised.

Antimicrobial Cationic Peptides↗

Apoptosis-associated generation of reactive oxygen intermediates and release of pro-inflammatory cytokines in human lymphocytes and granulocytes by extracts from the seeds of Acalypha wilkesiana.

Seeds from Acalypha wilkesiana (Euphorbiaceae) are an essential component of a complex plant mixture used empirically by traditional healers in Southwest Nigeria to treat breast tumours and inflammation. To investigate their biological properties, we incubated human lymphocytes and granulocytes with aqueous and ethanolic extracts of A. wilkesiana seeds (AWS). In lymphocytes, we observed an induction of apoptosis and generation of reactive oxygen intermediates (ROI), as measured by the oxidation of hydroethidine, within 2 h, while in granulocytes, an aqueous seed extract induced the oxidative burst and enhanced phagocytosis of Escherichia coli within 10-20 min. In the supernatants of 72-h cultured lymphocytes, AWS induced the release of the pro-inflammatory cytokines tumour necrosis factor-alpha and interleukin-6, and also T-cell-associated cytokines interleukin-5 and interferon-gamma. These preliminary results encourage further investigations of this drug with both cytotoxic and immunomodulating properties.

Apoptosis↗

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↗

[Development of lymphocyte subsets in tumor patients after subcutaneous administration of mistletoe extracts].

OBJECTIVE: In order to exclude the possibility that mistletoe therapy may result in immunosuppression, as indicated by a significant reduction of defined lymphocyte subsets, PATIENTS AND METHODS: peripheral blood cells of 23 tumour patients were treated subcutaneously with increasing concentrations of aqueous mistletoe extracts (Helixor(R)). RESULTS AND CONCLUSIONS: Within an observation period of 7 months, the relative amount of lymphocytes and the number of natural killer (NK) cells increased while the number of lymphocyte subsets (i. e. CD19+ B cells, CD4+ T helper cells, CD8+ CD28- suppressor cells, CD8+ CD28+ cytotoxic cells) and the proportion of CD25+ (activated) cells within T cells showed a statistically remarkable trend; due to the multiple test problem of statistical evaluation this trend is not allowed to be termed significant. The leucocytes decreased insignificantly within the observation period. However, we were unable to verify a suggested increase of defined lymphocyte subsets within 2-3 months after the onset of mistletoe treatment. Nevertheless, for the parameters CD19+ B cells, CD4+ T helper cells, CD8+ cells, CD8+ CD28+ cytotoxic cells and CD16+/CD56+ NK cells we observed statistically remarkable peaks within die 2nd and 3rd month of therapy, confirming the hypothesis. The responses to the extracts were obviously interindividually different; the immune responses especially of patients with a lower number of peripheral T cells were less significant as compared to those of patients with adequate T cell numbers. Surprisingly, even an increase of the drug concentration >3 ng mistletoe lectin (as determined within the whole plant extract) per kg body weight enhanced the number of CD4+ T helper cells. A decreased immunological reaction on mistletoe extracts was shown especially for patients with a reduced number of peripheral T cells, whereas patients with normal T-cell number were more reactive.

Adult↗

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↗

Effects of a phytopreparation from Helleborus niger on immunocompetent cells in vitro.

Extracts of Helleborus species are used as phytopreparations with immunostimulatory properties in Romanian traditional medicine. In Germany, Helleborus niger is used in homeopathy and as an adjuvant therapy in the treatment of tumor patients in anthroposophical medicine. In vitro application of an aqueous extract from Helleborus niger resulted in a slight induction of sister chromatid exchanges (SCE) in cultured peripheral blood mononuclear cells (PBMC) from healthy individuals, an effect associated with a slight increase of the [3H]thymidine uptake in the DNA of isolated lymphocytes. Since the cytokines interleukin (IL)-2 and tumor necrosis factor (TNF)-alpha were reported to increase the number of SCE, we measured the concentrations of these cytokines in the supernatants of cultured PBMC treated with the plant extract. Here, no significant changes were observed as compared with the controls, but a trend to higher supernatant concentrations of TNF-alpha in six out of ten individuals was noted. Compared with lymphocytes treated with the alkylating substance, cyclophosphamide, the increase of the SCE levels induced by the plant extract is weak. The relevance of this DNA destabilizing property remains to be clarified.

Cell Division↗

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↗

[Modernizing nursing with holistic nursing systems? Results of a formative assessment].

A project aiming at the implementation of a holistic nursing system was conducted on selected wards of a general hospital. The results of a formative evaluation are presented from a work psychological perspective. The reorganisation of nursing led to a higher degree of patient and employee orientation. Most aspects of nurses' work load were reduced but the improvement did not effect nurses' strain to the expected degree. Decision latitudes at the workplace were enlarged, whereas only few changes in decision latitudes were stated with regard to areas outside the ward. The project is discussed as a reflexive strategy of modernization; its success is a result of a process-oriented management which is able to react on unavoidable consequences in the reorganization process.

Burnout, Professional↗

Herpes virus (KSHV) associated Kaposi sarcoma in a 3-year-old child with non-HIV-induced immunodeficiency.

UNLABELLED: A 3-year-old boy of German descent suffered from two episodes of Streptococcus pneumoniae meningitis within 2 months. One month previously, the first skin lesion of Kaposi sarcoma (KS) had been observed behind his right ear. During the following 2 years KS disseminated not only mucocutaneously but also to visceral organs. Immunological evaluation revealed severe lymphocytopenia with reduced helper/suppressor T-cell ratio and impaired humoral immune response to pneumococci. Extensive laboratory tests gave no evidence for known immunocompromising infections. However, recently described DNA sequences from a Kaposi sarcoma-associated herpesvirus (KSHV) could be identified within skin tissue. As chemotherapy failed to stop tumour progression the patient was referred for bone marrow transplantation. Eighteen months later the KS is in remission and the patient in a good general condition. CONCLUSION: The case supports the hypothesis that KSHV is involved in the aetiology of KS. Bone marrow transplantation is possibly a therapeutic option for KS in patients with immunodeficiency not related to human immunodeficiency virus infection.

Bone Marrow Transplantation↗

Differences in the apoptosis-inducing properties of Viscum album L. extracts.

Viscum album L. (mistletoe) extracts are widely used in adjuvant cancer therapy. In contrast to purified components, such as mistletoe lectins and viscotoxins, whole plant extracts of mistletoe resulted in DNA stabilizations in cyclophosphamide-treated lymphocytes but also provided cytotoxicity in tumour cells and lymphocytes. The killing capacities of mistletoe extracts were host tree-specific and not correlated with mistletoe lectin or viscotoxin content. In human lymphocytes, only mistletoe lectins induced a pathway of apoptotic killing. Within 72 h, the lectin B chains also increased the number of lymphocytes undergoing apoptosis. This finding suggests that inhibition of protein synthesis by the A chain of the hololectin may accelerate a receptor-mediated killing pathway induced by the B chains. An unexpected finding was related to the mistletoe-mediated killing, which was more effective against CD8+T cells with an activated phenotype than CD19+ B cells and CD4+ T cells. In vitro treatment of human neutrophils with mistletoe resulted in a slight decrease of phagocytosis and burst activity. The observed dose-dependent occurrence of two neutrophil subsets with different burst activities indicates differences in their susceptibility to mistletoe and suggests the implication of an induction of the apoptotic killing pathway.

Animals↗