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C Radtke

Publications and source records attributed to C Radtke.

9 recordsLinked to original sources
PubMed2004

Immunosuppression following intestinal transplantation.

Acute rejection is still the main risk factor following intestinal transplantation. Potent immunosuppression decreases rejection frequency, but may increase immunosuppression-related complications. Isolated small intestinal transplantation was performed in 14 adult patients with short bowel syndromes. Immunosuppression included tacrolimus and rapamycin in combination with steroids for 6 months after ATG or daclizumab induction therapy. In addition to protocol biopsies, cellular immune status and soluble immune parameters were used to guide immunosuppression. CMV and EBV markers were determined on a routine basis. Ten of 14 patients (71%) survived for 1 to 38 months (median 26 months). Eight patients are at home, in good physical condition, completely on enteral nutrition. Among the 5 patients (36%) who developed acute rejection, 2 patients with early postoperative events underwent graft removal and 1 patient died due to multiple organ failure. Two patients developed severe acute rejection episodes at 10 and 24 months following transplantation. Both patients recovered following OKT3 rescue therapy and increased baseline immunosuppression with repeated methylprednisolone and infliximab treatment. Infections included peritonitis (n = 3), pneumonia (n = 3), central line infection (n = 5), urinary tract (n = 2), CMV (n = 2), and EBV (n = 4). Two patients developed anastomotic leaks at the esophageal and coloanal anastomosis. In conclusion, acute rejection episodes can be controlled by potent immunosuppression using tacrolimus in combination with rapamycin. Immunosuppression-associated complications, including infections, were in an acceptable range. However, even late after transplantation, reduction in immunosuppression may lead to severe rejection without major clinical symptoms.

Adult↗
PubMed2003

Hepatic gene expression patterns in thyroid hormone-treated hypothyroid rats.

Thyroid hormone (T3) is essential for normal development, differentiation and metabolic balance. We have performed DNA microarray experiments using hepatic RNA from hypothyroid and T3-treated hypothyroid rats in order to characterize T3-induced gene expression patterns after various time points (6, 24 and 48 h after the administration of the hormone). Sixty-two of 4608 different genes displayed a reproducible T3-response, and cluster analysis divided these differentially regulated genes into six expression patterns. Thirty-six genes were not significantly regulated within the first 24 h. Transient transfection experiments of eight late-induced gene promoters failed to detect a thyroid hormone response element within their regulatory elements, suggesting an indirect activation mechanism(s). In search for an intermediate factor of T3 action, we examined whether various rather ubiquitous transcription factors, peroxisome proliferator-activated receptors (PPARs) and coactivators of the PPARgamma coactivator 1 family (PGC-1) are regulated by T3. Only PPARgamma and PERC/PGC-1beta exhibit a significant T3-response within the first 6 h after treatment, identifying these factors as candidate components for mediating the late-induced expression pattern. Regulation of early-induced genes within the first 6 h after administration of T3 on transcript levels correlates with altered protein levels after 24 and 48 h in vivo.

Animals↗
PubMed2002

Limiting step involved in the thermal growth of silicon oxide films on silicon carbide.

Thermal growth of silicon oxide films on silicon carbide in O2 was investigated using oxygen isotopic substitution and narrow resonance nuclear reaction profiling. This investigation was carried out in parallel with the thermal growth of silicon oxide films on Si. Results demonstrate that the limiting steps of the thermal oxide growth are different in these two semiconductors, being diffusion limited in the case of Si and reaction limited in the case of SiC. This fact renders the growth kinetics of SiO2 on SiC very sensitive to the reactivity of the interface region, whose compositional and structural changes can affect the electrical properties of the structure.

Journal Article↗
PubMed2001

Two thyroid hormone-mediated gene expression patterns in vivo identified by cDNA expression arrays in rat.

Thyroid hormone (T3) is essential for normal development, differentiation and metabolic balance. Only a limited number of T3-target genes have been identified so far and their complex regulation pattern is poorly understood. We performed cDNA expression array hybridisation to identify T3-regulated genes and to investigate their expression pattern after various time points in vivo. Radioactively labelled cDNA was prepared from hepatic RNA of hypothyroid and hyperthyroid rats 6, 24 and 48 h after the administration of T3. Labelled cDNA probes were hybridised to rat Atlas Arrays. Twenty-three of 588 genes were shown to be differentially regulated, 18 of which were previously not known to be regulated by T3. The expression of 19 genes was verified by independent northern blot hybridisation. Two different expression time courses of T3 expression were observed. In a first expression profile ('early' expression) the transcription level of the target genes rises within 6 h, drops by 24 h and increases again within 48 h after the administration of T3. In a second expression profile ('late' expression) the mRNA level rose in the first 6 h and rose further by 48 h, indicating an additional regulation mechanism. Nuclear respiratory factor (NRF)-1 and peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1), but not NRF-2, were up-regulated within 6 h after T3 administration, suggesting NRF-1 and/or PGC-1 as key regulators for mediating the 'late' expression pattern.

Animals↗
PubMed2001

Hormonal regulation of multiple promoters of the rat mitochondrial glycerol-3-phosphate dehydrogenase gene: identification of a complex hormone-response element in the ubiquitous promoter B.

Rat mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) is regulated by multiple promoters in a tissue-specific manner. Here, we demonstrate that thyroid hormone (3,5,3'-tri-iodo-L-thyronine) and steroid hormone but not the peroxisome proliferator clofibrate and retinoic acid stimulate the activation of the ubiquitous promoter B in a receptor-dependent manner, whereas the more tissue-restricted promoters A and C are not inducible by these hormones. Thyroid hormone action is mediated by a direct repeat +4 (DR+4) hormone-response element as identified by deletion and mutation analyses of promoter B in transient transfection analyses. The DR+4 element was able to bind to an in vitro translated thyroid hormone receptor in band-shift and supershift experiments. The hormone-response element comaps with a recognition site for the transcription factor Sp1, suggesting complex regulation of this sequence element. Mutation of this Sp1-recognition site reduces the basal promoter B activity dramatically in HepG2 and HEK293 cells in transient transfection and abolishes the binding of Sp1 in band-shift experiments. As demonstrated by Western-blot experiments, administration of tri-iodothyronine to euthyroid rats increases hepatic mGPDH protein concentrations in vivo. As it has recently been reported that human mGPDH promoter B is not regulated by tri-iodothyronine, this is the first example of a differentially tri-iodothyronine-regulated orthologous gene promoter in man and rat.

Animals↗
PubMed2000

Multiple promoters direct the tissue-specific expression of rat mitochondrial glycerol-3-phosphate dehydrogenase.

The mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase (mGPDH) is an essential component of the glycerol phosphate shuttle which transfers reduction equivalents from the cytoplasm into the mitochondria. We analyzed the distribution of different exon 1-containing transcripts by RT-PCR in various tissues in vivo. Exon 1 a was predominantly expressed in brain, brown adipose tissue and pancreas, exon 1b was ubiquitously expressed, and exon 1c was exclusively expressed in testis. In transient transfection assays the ubiquitous promoter B showed a detectable activity, whereas promoters A and C were completely silent. A deletion mutational analysis located the basal promoter B activity to a 316 bp core sequence upstream of the transcription start site.

Animals↗