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Biomedical subjects

J Behrens

Publications and source records attributed to J Behrens.

At least 19 recordsLinked to original sources
PubMed2006

[The need for autonomy in the process of care-conceptual framework and research perspectives].

The article reflects the difference between independence and self-determination or autonomy in care relations. We consider that independence is only a fiction even for people with no functional limitations. Compared with this are people in need of care always confronted with professional interventions in their daily life which limit their self-determination. Even if participation and therefore also autonomy are part of the goal setting process in care a hierarchy in the relation of professional nurses and client is hardly to neglect. Quality of care with methods of evidence based nursing has must always take into account the client's implicit knowledge and experience which we call the "internal" evidence. Only the respect of the internal evidence can reduce the structural hierarchy between nurse and client. The article exemplifies these general conditions in care with nurse-client communication and the challenges of quality of care and quality of life.

Activities of Daily Living↗
PubMed2005

The role of the Wnt signalling pathway in colorectal tumorigenesis.

Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes. Mutations in the tumour suppressor APC (adenomatous polyposis coli) genes occur early in the development of CRC and lead to the stabilization of the Wnt pathway component beta-catenin and to the constitutive activation of Wnt signalling. Stabilizing mutations of beta-catenin can also lead to its accumulation, qualifying beta-catenin as a proto-oncogene. Here I will summarize the biochemical interactions occurring in Wnt signalling and describe how alterations in Wnt pathway components lead to CRC.

Colorectal Neoplasms↗
PubMed2004

[Smoking habits of employees and patients in the psychiatric department of a general hospital].

OBJECTIVE: Health promotion is becoming an increasingly more meaning in hospitals within their health promotion, primary and secondary prevention programmes. With reference to the preventive measures regarding nicotine dependence, it was first of all the objective of this study to determine the smoking habits of employees and patients in a psychiatric clinic. The question was also which implications for clinical practice could be drawn from this. METHODOLOGY: Apart from the Fagerstroem Test for nicotine dependence, a new questionnaire was developed, supported by the questionnaire "Smoke free in hospital", developed by the Federal Agency for Health Education, and implemented. 382 Patients and 484 employees were questioned. The statistical analysis was done using SPSS, and in addition thereto, the T-Test and the chi (2)-Test were used. RESULTS: Definite gender differences pertaining to smoking habits could be demonstrated. Women smoked less often (p < 0.001) and less (p < 0.01) than men and were less dependent on nicotine (p < 0.007). With increasing age, the number of smokers declined. In questioning the employees, it was clear, that there were no significant differences between doctors and nurses regarding their smoking habits. However, employees in the clinic working shifts were consuming more cigarettes daily (p < 0.044) and had a higher degree of dependence (p < 0.01). On questioning the patients, it was demonstrated that the number of smokers (92%) consuming cigarettes, dependence were significantly higher on the wards for dependence diseases. Overall it was clear that there were definite qualitative and quantitative differences in the smoking habits of both patients and employees. Patients smoke more often (p < 0.001) and are more dependent (p < 0.001) than employees. There were no differences between the two groups regarding the motivation to stop smoking (smokers willing to stop: 36%). However, more patients (38.5%) than employees (23.8%) expressed the opinion, that it is the task of the Hospital employees to regularly point out the risks of smoking. DISCUSSION: In the psychiatric clinic in question, the results demonstrated that cigarette consumption and nicotine dependency, for both patients and employees, are serious problems that can be transferred into comparable clinics and departments. Patients are more affected than employees. Other studies proved that psychiatric patients smoke twice as much as people without psychiatric diseases. CONCLUSION: Against the background, that health promotion and prevention should increasingly become the task of every hospital, further studies will be necessary to establish health promotive activities influencing smoking patients and employees. Specific treatment modalities regarding the motivation to change are still not available. Added to that, it must be tested within the German Health System, whether a clinically supervised smoking cessation programme complementing the treatment of the main diagnosis (a psychiatric disease) is demanded by the affected person, whether the clinic can finance it, and whether it can be successfully implemented.

Adolescent↗
PubMed2003

The Wnt signaling pathway and its role in tumor development.

Cancer development depends on the aberrant activation of signal transduction pathways that control cell growth and survival and play important roles in normal embryonic development. This review will focus on one of the most powerful pathways, the canonical Wnt signal transduction cascade, which has been originally described in vertebrate and non-vertebrate embryogenesis and subsequently associated with the development of a multitude of different tumor types, mainly of gastrointestinal origin. In recent years, a variety of novel interacting components and functions have been identified in the Wnt pathway revealing not only the complexity of Wnt signaling but also its potency. Here we will concentrate on the role of the Wnt pathway in cancer development with emphasis placed on the molecular defects known to promote neoplastic transformation in humans and in animal models.

Adenomatous Polyposis Coli Protein↗
PubMed2003

Nutritional interventions for preventing and treating pressure ulcers.

BACKGROUND: Pressure ulcers affect 10% of people in hospitals and older people are at highest risk. The correlation between nutritional intake and the development of pressure ulcers is suggested by several studies, but the results are inconsistent. OBJECTIVES: To evaluate the effectiveness of enteral and parenteral nutrition on the prevention and treatment of pressure ulcers. SEARCH STRATEGY: The Cochrane Wounds Group Specialised Trials Register and the Cochrane Central register of Controlled Trials were searched in September 2002. An additional search of PubMed and Cinahl and hand search of conference proceedings and journals was performed, bibliographies of relevant articles were examined and experts in the field as well as manufacturers were contacted in order to find additional literature that may be relevant. SELECTION CRITERIA: Randomised controlled trials evaluating the effectiveness of enteral or parenteral nutrition on the prevention and treatment of pressure ulcers by measuring the incidence of new ulcers, ulcer healing or changes in pressure ulcer severity. There were no restrictions on patients, setting, date, publication status or language. DATA COLLECTION AND ANALYSIS: Abstracts were independently inspected and full articles were obtained of potentially relevant studies. In case of disagreement advice was sought from a third person (AK). Data extraction and assessment of quality were undertaken by the three reviewers independently. MAIN RESULTS: Only 8 randomised controlled trials out of 16 potentially relevant articles were included. However, most of the 8 trials included are small and of poor methodological quality. PREVENTION: Four studies compared a combination of nutritional supplements, consisting of a minimum of energy and protein in different dosages, for the prevention of pressure ulcers. The largest study found that nutritional supplements reduced the number of new pressure ulcers (Bourdel-M 2000). The three smaller studies lacked power. TREATMENT: Four studies evaluated the effects of nutritional supplements for the treatment of existing pressure ulcers: one trial examined mixed nutritional supplements, one trial examined zinc, another the effect of proteins, and two studies compared ascorbic acid. The trials included are heterogeneous with regard to participants, interventions and outcomes; therefore it was considered inappropriate to perform a meta-analysis. REVIEWER'S CONCLUSIONS: It was not possible to draw any firm conclusions on the effect of enteral and parenteral nutrition on the prevention and treatment of pressure ulcers. Further trials of high methodological quality are necessary.

Aged↗
PubMed2001

Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas.

Medulloblastoma (MB) represents the most frequent malignant brain tumor in children. Most MBs appear sporadically; however, their incidence is highly elevated in two inherited tumor predisposition syndromes, Gorlin's and Turcot's syndrome. The genetic defects responsible for these diseases have been identified. Whereas Gorlin's syndrome patients carry germ-line mutations in the patched (PTCH) gene, Turcot's syndrome patients with MBs carry germ-line mutations of the adenomatous polyposis coli (APC) gene. The APC gene product is a component of a multiprotein complex controlling beta-catenin degradation. In this complex, Axin plays a major role as scaffold protein. Whereas APC mutations are rare in sporadic MBs, a hot-spot region of beta-catenin (CTNNB1) mutations was identified in a subset of MBs. To find out if Axin is also involved in the pathogenesis of sporadic MBs, we analyzed 86 MBs and 11 MB cell lines for mutations in the AXIN1 gene. Using single-strand conformation polymorphism analysis, screening for large deletions by reverse transcription-PCR, and sequencing analysis, a single somatic point mutation in exon 1 (Pro255Ser) and seven large deletions (12%) of AXIN1 were detected. This indicates that AXIN1 may function as a tumor suppressor gene in MBs.

Adolescent↗
PubMed2000

Apoptosis-induced cleavage of beta-catenin by caspase-3 results in proteolytic fragments with reduced transactivation potential.

Beta-catenin is a member of the Armadillo repeat protein family with a dual cellular function as a component of both the adherens junction complex and the Wnt/wingless signaling pathway. Here we show that beta-catenin is proteolytically cleaved during anoikis and staurosporine-induced apoptosis. Cleavage of beta-catenin was found to be caspase-dependent. Five cleavage products of beta-catenin were identified in vivo and after in vitro cleavage by caspase-3. Amino acid sequencing and mass spectrometry analysis indicated two caspase-3 cleavage sites at the C terminus and three further sites at the N terminus, whereas the central Armadillo repeat region remained unaffected. All beta-catenin cleavage products were still able to associate with E-cadherin and alpha-catenin and were found to be enriched in the cytoplasm. Functional analysis revealed that beta-catenin deletion constructs resembling the observed proteolytic fragments show a strongly reduced transcription activation potential when analyzed in gene reporter assays. We therefore conclude that an important role of the beta-catenin cleavage during apoptosis is the removal of its transcription activation domains to prevent its transcription activation potential.

Apoptosis↗
PubMed2000

Biochemical interactions in the wnt pathway.

The wnt signal transduction pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. The cytoplasmic component beta-catenin is central to the transmission of wnt signals to the nucleus: in the absence of wnts beta-catenin is constitutively degraded in proteasomes, whereas in the presence of wnts beta-catenin is stabilized and associates with HMG box transcription factors of the LEF/TCF family. In tumors, beta-catenin degradation is blocked by mutations of the tumor suppressor gene APC (adenomatous polyposis coli), or of beta-catenin itself. As a consequence, constitutive TCF/beta-catenin complexes are formed and activate oncogenic target genes. This review discusses the mechanisms that silence the pathway in cells that do not receive a wnt signal and goes on to describe the regulatory steps involved in the activation of the pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Hot spots in beta-catenin for interactions with LEF-1, conductin and APC.

Interactions between beta-catenin and LEF-1/TCF, APC and conductin/axin are essential for wnt-controlled stabilization of beta-catenin and transcriptional activation. The wnt signal transduction pathway is important in both embryonic development and tumor progression. We identify here amino acid residues in beta-catenin that distinctly affect its binding to LEF-1/TCF, APC and conductin. These residues form separate surface clusters, termed hot spots, along the armadillo superhelix of beta-catenin. We also show that complementary charged and hydrophobic amino acids are required for formation of the bipartite beta-catenin-LEF-1 transcription factor. Moreover, we demonstrate that conductin/axin binding to beta-catenin is essential for beta-catenin degradation, and that APC acts as a cofactor of conductin/axin in this process. Binding of APC to conductin/axin activates the latter and occurs between their SAMP and RGS domains, respectively.

Adenomatous Polyposis Coli Protein↗
PubMed2000

[Physician's anxiety and physician's elegance. Problems in dealing with cost reduction, education of general practitioners and optimal size of practice networks in a cross-national comparison].

The key reason for physicians networking in managed care is to get a better coping with uncertainty on action (treatment) decisions. The second reason for networking in managed care are financial benefits grounds. But this reason is very ambivalent. Three different action problems (role conflicts) in managed care network are to solved, which was also in single practices. In the lecture the decision strategies and decision resources has been compared. Observations are done using expert interviews, patient interviews and analysis of documents in USA, Germany and Switzerland. The first problem is the choosing of a cost reduction strategy which is not reducing the effectiveness. Such "ugly" solution strategies like exclusion of "expensive" patients and a rationing of necessary medical services in a kind of McDonalds network of physicians will fail the target. The optimost way is a saving of all unnecessary medical even injourious performances. The chosen cost reduction strategy is not real visible from outside but in fact limited cognizable and controllable. Evidence based health care can be a resource of treatment decisions and could train such decisions but it will not substitute these decisions. The second problem is the making of real family practitioners as gatekeepers. Knowledge about the care system is still not making a real family practitioner, even if this is the minimum condition of their work. Also contractual relationships between insurance and doctor as a gatekeeper or financial incentives for patients are still making not a real family practitioner as a gatekpeeper. Only throughout the trust of patients supported by second opinions is making the real family practitioner as a gatekeeper. "Doctor hopping" could be the reaction by scarcity of trustworthy family practitioners as gatekeepers. The third problem is the choosing of the optimal scale of a network due to the very different optimal size of networks regarding the requirement of risk spreeds, of the motivated engagement, of competition, incentives of inclusion of insurantes, they always need other net sizes. But it is possible, for each requirement there could function different networks. A practice (doctor's office) can be a member in different networks in several levels. The social transition from a small office to a network of offices is in all business lines a cultural shock involving not only benefits also psychical and social distress. In this there is no difference between health or agriculture or each other business of trade and industry. The destiny of the joint doctor's offices in Germany suggest due to a very serious power to scatter this networks. The comparative analysis of conflicts, strains, resources and strategies of associations and networks could yield from a developed methodical repository in sociology and social psychology what exists since 40 years (see also Meyer--in this journal). But therefore must be included also the action problems, which are only mentioned in passing of the according profession horizon.

Cost Control↗
PubMed2000

Control of beta-catenin signaling in tumor development.

The wnt signal transduction pathway is involved in various differentiation events during embryonic development and leads to tumor formation when aberrantly activated. The wnt signal is transmitted to the nucleus by the cytoplasmic component beta-catenin: in the absence of wnts, beta-catenin is constitutively degraded in proteasomes, whereas in the presence of wnts beta-catenin is stabilized and can associate with HMG box transcription factors of the LEF/TCF family. The LEF/TCF/beta-catenin complexes activate specific wnt target genes. In tumors, beta-catenin degradation is blocked by mutations of beta-catenin or of the tumor suppressor gene product APC. As a consequence, beta-catenin is stabilized, constitutive complexes with LEF/TCF factors are formed, and oncogenic target genes, such as c-myc, cyclin D1, and c-jun, are activated. Thus, control of beta-catenin is a major regulatory event in normal wnt signaling and during tumor formation. It has been found that a multiprotein complex assembled by the cytoplasmic component conductin induces degradation of cytoplasmic beta-catenin. The complex includes APC, the serine/threonine kinase GSK3 beta, and beta-catenin, which bind to conductin at distinct domains. In colon carcinoma cells, forced expression of conductin downregulates beta-catenin, whereas in normal cells mutants of conductin that are deficient in complex formation stabilize beta-catenin. Fragments of APC that contain a conductin-binding domain also block beta-catenin degradation. In Xenopus embryos, conductin inhibits the wnt pathway. In situ hybridization analysis shows that conductin is expressed in various embryonal tissues known to be regulated by wnts, such as the developing brain, mesenchyme below the epidermis, lung mesenchyme, and kidney. It is suggested that conductin controls wnt signaling by assembling the essential components of the beta-catenin degradation pathway. Alterations of conductin function may lead to tumor formation.

Cell Transformation, Neoplastic↗
PubMed2000

Cross-regulation of the Wnt signalling pathway: a role of MAP kinases.

The Wnt signal transduction pathway regulates various aspects of embryonal development and is involved in cancer formation. Wnts induce the stabilisation of cytosolic (beta)-catenin, which then associates with TCF transcription factors to regulate expression of Wnt-target genes. At various levels the Wnt pathway is subject to cross-regulation by other components. Recent evidence suggests that a specific MAP kinase pathway involving the MAP kinase kinase kinase TAK1 and the MAP kinase NLK counteract Wnt signalling. In particular, homologues of TAK1 and NLK, MOM-4 and LIT-1, negatively regulate Wnt-controlled cell fate decision in the early Caenorhabditis elegans embryo. Moreover, TAK1 activates NLK, which phosphorylates TCFs bound to (beta)-catenin. This blocks nuclear localization and DNA binding of TCFs. Since TAK1 is activated by TGF-(beta) and various cytokines, it might provide an entry point for regulation of the Wnt system by other pathways. In addition, alterations in TAK1-NLK might play a role in cancer.

Animals↗
PubMed2000

Rapid flow cytometric test for the diagnosis of membrane cytoskeleton-associated haemolytic anaemia.

The flow cytometric test measures the fluorescence intensity of intact red cells labelled with the dye eosin-5-maleimide, which reacts covalently with Lys-430 on the first extracellular loop of band 3 protein. In this study, red cells from patients with hereditary spherocytosis (HS), congenital dyserythropoietic anaemia type II, South-east Asian ovalocytosis and cryohydrocytosis have produced a greater degree of reduction of mean channel fluorescence readings than those for other patient groups and normal controls. The predictive value of this test for membrane abnormality was compared with the results obtained from the sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) method, which is currently the reference laboratory test for the identification of membrane protein deficiencies in hereditary spherocytosis and for the detection of spectrin variants in hereditary elliptocytosis. The dye method is a reliable, speedy diagnostic test (2 h from sample collection to result) for HS with a sensitivity of 92.7% and a specificity of 99.1%. Thus, it will serve well as a first-line screening test for the diagnosis of hereditary spherocytosis in routine haematology.

Adult↗
PubMed1999

Immunohistological analysis of E-cadherin, alpha-, beta- and gamma-catenin expression in colorectal cancer: implications for cell adhesion and signaling.

Intercellular adhesion mediated by the E-cadherin/catenin complex is a prerequisite for epithelial integrity and differentiation. In carcinomas, E-cadherin function is frequently disturbed, and has been suggested to increase invasion and metastasis of tumour cells. beta-catenin has also been implicated in signaling pathways essential for tumour formation. We analysed the E-cadherin/catenin adhesion system of colorectal tumours at different clinical stages. In primary carcinomas (n = 91), there was a frequent reduction in E-cadherin (44%) and alpha-catenin expression (36%). In contrast, beta-catenin and gamma-catenin expression were seldom reduced (4% and 15%, respectively). Similar expression patterns were observed in liver metastases from unrelated colorectal tumours (n = 27). There was a significant relationship between loss of E-cadherin and alpha-catenin expression and poorly differentiated (G3-4) tumours. Our results suggest that reduction of E-cadherin/alpha-catenin expression is a frequent event in primary and metastatic colorectal carcinomas. Furthermore, beta-catenin expression remains normal in colorectal cancer, suggesting the essential role of beta-catenin in signaling pathways.

Cadherins↗
PubMed1999

Cadherins and catenins: role in signal transduction and tumor progression.

Cadherins are transmembrane cell-cell adhesion molecules which are connected to the cytoskeleton by association with the cytoplasmic proteins, alpha-, beta-, and, gamma-catenin (plakoglobin). Beta-catenin has an additional role in the wnt signal transduction pathway in which it transmitts signals to the cell nucleus in complexes with transcription factors of the LEF-1/TCF family. The cell adhesion function of the epithelial E-cadherin is frequently disturbed in carcinomas either by downregulation or by mutation of the E-cadherin/catenin genes. The signaling function of beta-catenin is activated in tumors by mutations of beta-catenin or of the tumor suppressor gene product APC. In this review I will give an introduction to the structure and function of the cadherin/catenin complex and summarize findings which support a decisive role of these components in the development of cancer.

Amino Acid Sequence↗