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Biomedical subjects

Christine Schäfer

Publications and source records attributed to Christine Schäfer.

8 recordsLinked to original sources
PubMed2007

Osmotic regulation of betaine homocysteine-S-methyltransferase expression in H4IIE rat hepatoma cells.

Cell hydration changes critically affect liver metabolism and gene expression. In the course of gene expression studies using nylon cDNA-arrays we found that hyperosmolarity (405 mosmol/l) suppressed the betaine-homocysteine methyltransferase (Bhmt) mRNA expression in H4IIE rat hepatoma cells. This was confirmed by Northern blot and real-time quantitative RT-PCR analysis, which in addition unraveled a pronounced induction of Bhmt mRNA expression by hypoosmotic (205 mosmol/l) swelling. Osmotic regulation of Bhmt mRNA expression was largely paralleled at the levels of Bhmt protein and enzymatic activity. Like hyperosmotic NaCl, hyperosmotic raffinose but not hyperosmotic urea suppressed Bhmt mRNA expression, suggesting that cell shrinkage rather than increased ionic strength or hyperosmolarity per se is the trigger. Hypoosmolarity increased the expression of a reporter gene driven by the entire human BHMT promoter, whereas destabilization of BHMT mRNA was observed under hyperosmotic conditions. Osmosensitivity of Bhmt mRNA expression was impaired by inhibitors of tyrosine kinases and cyclic nucleotide-dependent kinases. The osmotic regulation of BHMT may be part of a cell volume-regulatory response and additionally lead to metabolic alterations that depend on the availability of betaine-derived methyl groups.

Animals↗
PubMed2006

How to successfully implement E-learning for both students and teachers.

RATIONALE AND OBJECTIVES: Electronic learning (e-learning) may provide a means to enhance learning efficacy. However, introduction of e-learning often fails. We describe a strategy of how an e-learning curriculum was successfully implemented. MATERIALS AND METHODS: The curriculum was designed based on published evidence. It consists of self-directed learning, an online discussion forum, and discussion rounds. The e-content in nuclear medicine and radiotherapy was produced by the k-MED team of medical authors, web designers, and psychologists. The online courses were delivered via a dedicated learning management system. The e-content for diagnostic radiology and physics was provided as PDF/HTML script by the respective teachers who objected to participate in the k-MED project. The exam was taken online. Online evaluation of the curriculum by the students was taken at the end of the course. RESULTS: The new curriculum proved very effective. The time for the preparation for the clinical part of the radiology course could be reduced from 4 to 2 weeks. The students particularly enjoyed the self-directed learning. Although the material provided by k-MED received 90%-99% positive scores, the HTML and PDF scripts scored worse (13%-67% positive ratings). The positive results of the evaluation convinced the teachers responsible for physics and diagnostic radiology to participate in k-MED. CONCLUSIONS: As our example shows, new e-learning curricula can successfully be introduced. The strategy of implementation should be based on the existing evidence from the literature. The new curriculum helped to increase the efficacy of teaching and save time as the duration of the respective part of the course could be reduced by half.

Computer-Assisted Instruction↗
PubMed2006

[Implementation of the multi-center basis documentation CL-BaDo for conciliar and liaison services: generating data for internal quality management and cost calculation].

In the German DRG system the funding of CL services is not ensured. The documentation of psychiatric comorbidity and CL care delivery is a pre-condition to the development of funding models for CL-services. A task force of several German psychosomatic associations (German College of Psychosomatic Medicine, German Society of Psychosomatic Medicine and Psychotherapy, General Medical Society for Psychotherapy) developed a new documentation form for CL-services (CL-BaDo). The pilot study explored the multicenter implementation of CL-BaDo and the use of the documentation form for quality management and cost calculation. Over a period of at least three months, participating CL-services documented all CL cases consecutively with the CL-BaDo. One site applied full electronic data processing. 2116 CL cases from eight psychosomatic CL-services were analysed. The CL-BaDo is a time-efficient, feasible and acceptable documentation form for CL-service delivery. The full electronic data processing enables networking with a hospital information system to produce higher data quality. The data of CL-BaDo can be used locally for quality management, development of management strategies and communication with consultants, as well as nationwide for health policy questions and research.

Austria↗
PubMed2005

An alternative approach for exercise prescription and efficacy testing in patients with chronic heart failure: a randomized controlled training study.

BACKGROUND: Prescription of endurance training and documentation of its efficacy in patients with chronic heart failure (CHF) is usually done with reference to maximal ergometric measurements which are subject to form on the day changes and motivational influences. However, the use of submaximal parameters might represent an alternative approach. METHODS: This was tested in 54 patients with CHF (57 +/- 10 years, NYHA II: n = 40; NYHA III: n = 14) who were randomized into training (T; n = 26) or control group (CO; n = 28). Training consisted of 45 minutes cycling at an intensity corresponding to the anaerobic threshold (AT) and was conducted for 12 weeks, 4 to 5 times per week. Cardiorespiratory exercise testing was done before and after the experimental phase. Changes in well-being were investigated using a 5-point Likert scale. RESULTS: A significant rightward shift in the heart rate curve was demonstrated in T compared with CO (P = .01; T: decrease in resting heart rate by 8 per minute, during exercise by 7 to 11/min; CO: -1 and -1 to -3 per minute, respectively). Anaerobic threshold increased significantly by 11.6% in T (+0.11 +/- 0.11 L min(-1) oxygen uptake) compared with CO (-0.02 +/- 0.10 L min(-1)). Positive changes in well-being were significantly larger in T (P < .01). CONCLUSIONS: In patients with CHF, training can be prescribed and its efficacy can be evaluated by the exclusive use of submaximal parameters. Anaerobic threshold represents an appropriate training intensity in this population.

Aged↗
PubMed2003

Osmotic regulation of insulin-induced mitogen-activated protein kinase phosphatase (MKP-1) expression in H4IIE rat hepatoma cells.

A contribution of intracellular dehydration to insulin resistance has been established in human subjects and in different experimental systems. Here the effect of hyperosmolarity (405 mosmol/l) on insulin-induced mitogen-activated protein (MAP) kinase phosphatase (MKP)-1 expression was studied in H4IIE rat hepatoma cells. Insulin induces robust MKP-1 expression which correlates with a vanadate-sensitive decay of extracellular-signal-regulated kinase (Erk-1/Erk-2) activity. Hyperosmolarity delays MKP-1 accumulation by insulin and this corresponds to impaired MKP-1 synthesis, whereas MKP-1 degradation remains unaffected by hyperosmolarity. Rapamycin, which inhibits signalling downstream from the mammalian target of rapamycin (mTOR) and a peptide inhibiting protein kinase C (PKC) zeta/lambda abolish insulin-induced MKP-1 protein but not mRNA expression, suggesting the involvement of the p70 ribosomal S6 protein kinase (p70S6-kinase) and/or the eukaryotic initiation factor 4E-binding proteins (4E-BPs) as well as atypical PKCs in MKP-1 translation. Hyperosmolarity induces sustained suppression of p70S6-kinase and 4E-BP1 hyperphosphorylation by insulin, whereas insulin-induced tyrosine phosphorylation of the insulin receptor (IR) beta subunit and the IR substrates IRS1 and IRS2, recruitment of the phosphoinositide 3-kinase (PI 3-kinase) regulatory subunit p85 to the receptor substrates as well as PI 3-kinase activation, and Ser-473 phosphorylation of protein kinase B and Thr-410/403 phosphorylation of PKC zeta/lambda are largely unaffected under hyperosmotic conditions. The hyperosmotic impairment of both, MKP-1 expression and p70S6-kinase hyperphosphorylation by insulin is insensitive to K(2)CrO(4), calyculin A and vanadate, and inhibition of the Erk-1/Erk-2 and p38 pathways. The suppression of MKP-1 may further contribute to insulin resistance under dehydrating conditions by allowing unbalanced MAP kinase activation.

Animals↗
PubMed2003

Opposite effects of rofecoxib on nuclear factor-kappaB and activating protein-1 activation.

Rofecoxib is a selective cyclooxygenase (COX)-2 inhibitor approved for the treatment of pain and inflammation in rheumatoid and osteoarthritis. Daily doses between 12.5 and 50 mg were found to reduce pain and inflammation, however, without a clear dose-effect relationship. Interestingly, rofecoxib treatment is associated with an unexpected incidence of renal adverse events compared with other COX inhibitors. Here, the effects of rofecoxib on the transcription factors nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) were analyzed to find out whether transcriptional changes might explain the lack of clear dose dependency and the occurrence of renal side effects. In vitro, rofecoxib dose dependently inhibited DNA binding capacity of NF-kappaB at doses of 10 to 100 microM, whereas the binding activity of AP-1 was considerably increased at 100 microM. In vivo, the anti-inflammatory effect of rofecoxib was equal at 1 and 10 mg/kg, whereas 50 mg/kg caused a significant further reduction of a zymosan-induced paw edema. This was associated with a clear decrease of inducible nitric oxide synthase (iNOS) protein expression in the spinal cord at this dose. At 1 and 10 mg/kg, however, iNOS was increased but COX-2 was decreased. Thus, the expression of proinflammatory proteins was similarly inconsistent as transcription factor regulation. In conclusion, the opposite effects of rofecoxib on AP-1 and NF-kappaB may explain the lack of clear dose dependency with rofecoxib in clinical studies or animal experiments. The effects on AP-1 may possibly affect renal sodium transport because certain renal sodium channels are regulated through AP-1. Transcription factor regulation might therefore influence both wanted and unwanted effects of rofecoxib.

Animals↗
PubMed2002

Expression and regulation of the Na(+)/K(+)/2Cl(-) cotransporter NKCC1 in rat liver and human HuH-7 hepatoma cells.

The expression of sodium potassium chloride cotransporter 1 (NKCC1) was studied in different liver cell types. NKCC1 was found in rat liver parenchymal and sinusoidal endothelial cells and in human HuH-7 hepatoma cells. NKCC1 expression in rat hepatic stellate cells increased during culture-induced transformation in the myofibroblast-like phenotype. NKCC1 inhibition by bumetanide increased alpha(1)-smooth muscle actin expression in 2-day-cultured hepatic stellate cells but was without effect on basal and platelet-derived-growth-factor-induced proliferation of the 14-day-old cells. In perfused rat liver the NKCC1 made a major contribution to volume-regulatory K(+) uptake induced by hyperosmolarity. Long-term hyperosmotic treatment of HuH-7 cells by elevation of extracellular NaCl or raffinose concentration but not hyperosmotic urea or mannitol profoundly induced NKCC1 mRNA and protein expression. This was antagonized by the compatible organic osmolytes betaine or taurine. The data suggest a role of NKCC1 in stellate cell transformation, hepatic volume regulation, and long-term adaption to dehydrating conditions.

Animals↗