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B Sauer

Publications and source records attributed to B Sauer.

At least 19 recordsLinked to original sources
PubMed2006

Paclitaxel encapsulated in cationic lipid complexes (MBT-0206) impairs functional tumor vascular properties as detected by dynamic contrast enhanced magnetic resonance imaging.

Cationic lipid complexes have been shown to be bound and internalized selectively by angiogenic tumor endothelial cells after intravenous injection. Based on this phenomenon, the chemotherapeutic agent paclitaxel was encapsulated into these lipid complexes providing a vascular targeting agent (MBT-0206). As noninvasive imaging techniques are of critical importance for optimizing antivascular cancer treatment in the clinic, we have evaluated the antivascular effects of MBT-0206 in the A-MEL-3 solid tumor model using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Twenty-four hours after three intravenous applications of MBT-0206, tumors of treated animals demonstrated a significant decrease of intratumoral blood volume and an increase of vascular permeability in comparison to size-matched control tumors. In contrast, animals treated with conventional paclitaxel given as Taxol at equal drug dose did not show any significant differences in vascular parameters acquired by DCE-MRI in comparison to controls. Immunohistological analysis confirmed a significant reduction of microvessel density in MBT-0206 treated tumors. Moreover, a significant increase of intratumoral microvascular occlusion following MBT-0206 treatment was observed compared to controls and paclitaxel treated animals. In conclusion, antivascular tumor therapy with MBT-0206 significantly impairs functional tumor microcirculation. DCE-MRI is a promising tool to quantify the antivascular effects of MBT-0206 during treatment.

Animals↗
PubMed2006

[Treatments of prostate carcinoma and imaging follow up].

Multiple treatments are proposed to cure prostate carcinoma. Radical prostatectomy is the classical option for localized tumor. However radiotherapy can be proposed in such circumstances with the argument of a less invasive procedure with similar results. High Intensity Focalised Ultrasound (HIFU) is a new technique available for similar staging of the carcinoma with good results. Follow up is based on biological evaluation of PSA. Imaging studies are required only in cases of abnormal level. Endorectal Ultrasonography with biopsies is useful after radical surgery. Indications for MRI study is mainly to differentiate a localized from a general recurrence.

Aged↗
PubMed2005

Radiofrequency and laser ablation of spinal lesions.

Radiofrequency current and laser energy can be delivered locally through electrode-needle or optical fiber inserted in the tissue and allows local ablation of tissues, up to a volume of 4 to 5 cm in diameter with one application or vaporizes tissue. Tumor ablation guided with medical imaging proved a high local efficacy over 90% for tumors less than 25 mm in the liver, lung, and kidney. The spinal applications of the thermal energy of RF and laser are reported in this paper. First, the tumor ablation is reviewed with malignant and benign tumors. In malignant tumors, radiofrequency is very efficient in local tumor control and in pain management. The second part of this paper is devoted to disk diseases where laser and RF techniques increase their applications. The technique, indications and results of these techniques are reported and illustrated.

Back Pain↗
PubMed2005

Sphingosine 1-phosphate is involved in cytoprotective actions of calcitriol in human fibroblasts and enhances the intracellular Bcl-2/Bax rheostat.

Calcitriol is originally known to decrease proliferation rates of several carcinoma cells, partly via induction of apoptosis. On the other hand, the secosteroid is revealed to protect some cell types like thyrocytes, HL-60 cells and melanocytes against programmed cell death. Here we report that calcitriol despite its strong antiproliferative effect on human dermal fibroblasts did not induce apoptosis in these cells. In contrast, calcitriol possessed an antiapoptotic action in dermal fibroblasts. Thus, the ability of the apoptotic stimuli TNFalpha/actinomycin and C2-ceramides (C2-Cer) to induce programmed cell death was drastically diminished in the presence of calcitriol. Moreover, we identified sphingosine 1-phosphate (S1P) as a downstream mediator of calcitriol for its cytoprotective property. Thus, the secosteroid could not protect fibroblasts from apoptosis in the presence of N,N-dimethylsphingosine (DMS), which inhibits sphingosine kinase, the crucial enzyme to form S1P. Like calcitriol, S1P in different concentrations did not induce fibroblast apoptosis and moreover drastically decreased the rates of apoptotic cells after treatment with TNFalpha1/actinomycin. As S1P has been identified to modify the Bcl-2/ Bax ratio in epithelial cells and keratinocytes, we also measured the expression of these proteins in dermal fibroblasts revealing an increased Bcl-2 level after stimulation with S1P while the Bax protein expression was not modified. In conclusion, calcitriol H was revealed to protect human fibroblasts from apoptosis by formation of S1P resulting in a changed Bcl-2/Bax ratio.

Annexin A5↗
PubMed2004

Glucocorticoids mediate differential anti-apoptotic effects in human fibroblasts and keratinocytes via sphingosine-1-phosphate formation.

Glucocorticoids are potent anti-inflammatory and immunomodulatory drugs which also induce growth inhibition in a variety of cell types. For this reason long-term treatment of inflammatory skin diseases may result in irreversible skin atrophy. To elucidate whether the antiproliferative action of glucocorticoids in fibroblasts is accompanied by induction of apoptosis we investigated the influence of dexamethasone (DEX) on both parameters. Interestingly, we revealed that growth inhibitory concentrations of this glucocorticoid did not induce fibroblast apoptosis. Moreover, DEX protected these cells from apoptosis induced by tumor necrosis factor alpha (TNFalpha)/actinomycin, UV-irradiation, and cell permeable ceramides. These findings are in contrast to the lack of anti-apoptotic effects detected in keratinocytes. Although DEX inhibited TNFalpha mediated nuclear factor-kappa (NF-kappaB) activity in fibroblasts, this mechanism was not involved in its cytoprotection as it was verified by specific NF-kappaB inhibitors. Therefore, we looked for alternative intracellular mediators. Coincubation of fibroblasts with the sphingosine kinase inhibitor N,N-dimethylsphingosine, which blocks formation of the sphingolipid degradation product sphingosine-1-phosphate (S1P), abrogated the protective glucocorticoid effect almost completely. As preincubation with S1P reduced the number of apoptotic cells after stimulation with TNFalpha/actinomycin and moreover DEX increased the intracellular S1P content a role of this sphingolipid in the cytoprotection by DEX is suggested.

Apoptosis↗
PubMed2004

Protamine enhances uptake of cationic liposomes in angiogenic microvessels.

INTRODUCTION: Cationic liposomes have been shown to target angiogenic endothelial cells of solid tumours. Supposing a charge-related mechanism might be responsible for liposome-endothelial interaction, we investigated the effect of intravenous pre-injection of the charged molecules protamine, a polycationic protein, and fucoidan, a polyanionic polysaccharide on the accumulation of cationic liposomes within the blood vessels of a solid tumour. MATERIALS AND METHODS: Experiments were performed using the amelanotic hamster melanoma A-Mel-3 growing in a dorsal skinfold chamber of hamsters. Accumulation of fluorescently-labelled cationic liposomes was quantified by intravital macroscopy and digital image analysis of tumour (t) and surrounding normal host tissue (n) over an observation period of 6 h. All animals received an i.v. injection of cationic liposomes. Animals of the control group were pre-treated with an i.v. injection of 0.9% saline, while animals of group 2 received positively charged protamine and animals of group 3 negatively charged fucoidan prior to liposome injection. RESULTS: In control animals i.v. injection of cationic liposomes revealed a preferential targeting of the tumour vessels, indicated by a maximal t/n ratio of 2.2 +/- 0.24 and a maximal fluorescence intensity (fmax) corresponding to the tumour of 66 +/- 12 [% standard]. While there were no significant differences of liposome accumulation within normal host tissue, accumulation of cationic liposomes within the tumour was significantly enhanced after the pre-administration of protamine (fmax: 117 +/- 12 [% standard]). The t/n ratio was significantly increased in protamine pre-treated animals (5.3 +/- 1.7) in comparison to control and fucoidan treated animals. In contrast, pre-injection of fucoidan resulted in reduced maximal fluorescence intensities in tumour (47 +/- 8 [% standard]) and normal surrounding host tissue. CONCLUSION: Pre-administration of protamine increases the accumulation of cationic liposomes in a solid tumour animal model causing an increased selectivity of cationic liposomes in targeting angiogenic microvessels.

Animals↗
PubMed2004

[Buried bumper - a new method of non-surgical removal].

Buried bumper syndrome is a rare complication among patients with PEG for long-term feeding. Tight fixation of the external bumper causes pressure necrosis beneath the internal bumper. This leads to the internal bumper's penetration of the deeper gastric wall, where it is completely overgrown by gastric mucosa. A method is shown how the buried bumper can be removed without an operation. This method was used successfully in seven patients. The buried bumper syndrome can be avoided with careful precautions.

Aged↗
PubMed2004

Dermcidin is constitutively produced by eccrine sweat glands and is not induced in epidermal cells under inflammatory skin conditions.

BACKGROUND: Antimicrobial peptides (AMPs) are important effector molecules of innate immunity, protecting epithelial surfaces of multicellular organisms. In human skin two classes of AMPs-the beta-defensins and the cathelicidins-are produced by keratinocytes primarily under inflammatory conditions. In contrast, dermcidin (DCD), a recently discovered AMP with broad-spectrum activity, is expressed in eccrine sweat glands and transported via sweat to the epidermal surface. OBJECTIVES: To investigate whether DCD expression is induced under inflammatory conditions in epidermal keratinocytes. METHODS: Lesional skin of the inflammatory skin diseases atopic dermatitis, psoriasis and lichen planus was analysed by immunohistochemistry using a polyclonal anti-DCD antiserum. We also examined whether DCD RNA expression is induced in cultured human keratinocytes, fibroblasts, melanocytes and melanoma cells. RESULTS: Whereas DCD was constitutively expressed in eccrine sweat glands of all skin biopsies, we found that, independent of the type of the inflammatory skin lesion, DCD protein expression was not induced in human epidermal keratinocytes. In contrast, beta-defensin 2 was expressed in epidermal keratinocytes of inflammatory human skin, but not in keratinocytes of healthy human skin. Upon stimulation of the cultured cells with 12-O-tetradecanoyl-phorbol-13-acetate, tumour necrosis factor-alpha, lipopolysaccharide or H2O2, DCD mRNA expression was not detected in primary keratinocytes, fibroblasts and melanocytes, but was detected in MeWo and SKMEL28 melanoma cells. CONCLUSIONS: These results indicate that, unlike human cathelicidins and beta-defensins which are inducible peptides that primarily function in response to injury and inflammation, DCD is exclusively part of the constitutive innate defence of human skin. By modulating surface colonization, DCD may help to prevent local and systemic invasion of pathogens.

Adult↗
PubMed2004

New chimera proteins for fluorescence correlation spectroscopy.

A new class of chimera proteins has been developed. They are ideally suited for detection by fluorescence correlation spectroscopy (FCS), a new technology to analyze molecular interactions. The molecular structure of these chimera proteins consists of four domains: a N-terminal (His)6-tag for affinity chromatography followed by an eight amino acid epitope for immunodetection, a polypeptide affinity domain (ADF) for target specific interaction and a C-terminal Green Fluorescent Protein (GFPuv) for reporting of interaction with the target by FCS. We designed, prepared and characterized a prototype of ADF-GFP proteins capable of specific interaction with DNA fragments bearing nuclear factor (NF)-kappaB sites. ADF NF-kappaB p50 and a non-DNA-binding deletion mutant (p35) combined with GFPuv were inserted in a procaryotic vector and expressed in E. coli. Following affinity purification the fluoroproteins p50-GFPuv and p35-GFPuv were employed in specific protein-protein and protein-DNA interaction studies. FCS analysis as well as EMSA showed that p50-GFPuv revealed a fully functional ADF. We present a model for the preparation of GFP fusion proteins capable of specific interaction with proteins, lipids or nucleic acids. The rational design allows any polypeptide fragment to be incorporated into the chimeric protein. So a new series of bio-molecules with different binding specificities and assays can be developed.

Blotting, Western↗
PubMed2003

[A puzzling circulatory failure after total hip replacement].

The diagnosis of acute circulatory failure in the postoperative course of hip replacement must concentrate on frequent complications, but rare complications requiring specific treatment must also be diagnosed. We report on the occurrence of a case of acute adrenal insufficiency subsequent to enoxaparin-induced type II thrombocytopenia. A delay was necessary to establish a correct diagnosis for two reasons: (1) an unusual clinical presentation and (2) an underevaluation of the medical risk during the preoperative visit. The evolution was nevertheless favorable after prescription of steroids that had to be prescribed chronically.

Acute Disease↗
PubMed2003

[Palliative laser therapy of colorectal cancer with sustained local tumor removal].

Laser photocoagulation is an established palliative therapeutic method in advanced colorectal cancer. In most cases tumor obstruction of the colonic lumen and symptoms like bleeding, secretion and diarrhoea can be improved or prevented. Even curative tumor therapy of some patients has been reported, particularly in cases with superficial growth of the tumor. We report about an elderly female patient with locally advanced invasive carcinoma of the rectosigmoidal junction. This tumor and a polypoid carcinoma of the sigmoid, possibly in combination with snare resection, were persistently removed by laser photocoagulation.

Adenocarcinoma↗
PubMed2001

Neuron-specific expression of Cre recombinase during the late phase of brain development.

Gene targeting to disrupt gene expression in a temporal and spatial manner in a specific tissue using Cre recombinase-mediated gene inactivation has been proven to be useful to study in vivo gene function. To delete genes specifically in neurons during the late phase of brain development, we have generated transgenic mouse lines that express Cre recombinase under the control of the murine neurofilament-H (mNF-H) gene promoter. In this study, we report that one of these mouse lines expresses Cre recombinase specifically in the neurons of the brain and spinal cord during the late stage of their development. The transgenic line displays specific excision of the loxP-flanked gene in the neurons just after embryonic day 18.5 (E.18.5), which coincides with the later phase of brain maturation including spinal cord and olfactory bulb area. This mNF-H-cre transgenic mouse line will be valuable for studying in vivo functions of neuron-specific genes, particularly, defining their precise roles in the mature nervous system using conditional gene targeting strategies.

Age Factors↗
PubMed2001

Dermcidin: a novel human antibiotic peptide secreted by sweat glands.

Antimicrobial peptides are an important component of the innate response in many species. Here we describe the isolation of the gene Dermcidin, which encodes an antimicrobial peptide that has a broad spectrum of activity and no homology to other known antimicrobial peptides. This protein was specifically and constitutively expressed in the sweat glands, secreted into the sweat and transported to the epidermal surface. In sweat, a proteolytically processed 47-amino acid peptide was generated that showed antimicrobial activity in response to a variety of pathogenic microorganisms. The activity of the peptide was maintained over a broad pH range and in high salt concentrations that resembled the conditions in human sweat. This indicated that sweat plays a role in the regulation of human skin flora through the presence of an antimicrobial peptide. This peptide may help limit infection by potential pathogens in the first few hours following bacterial colonization.

Amino Acid Sequence↗
PubMed2001

Conditional gene knockout using Cre recombinase.

Cre recombinase has become an important instrument for achieving precise genetic manipulation in mice. Many of these desired genetic manipulations rely on Cre's ability to direct spatially and temporally specified excision of a predesignated DNA sequence that has been flanked by directly repeated copies of the loxP recombination site. Success in achieving such conditional mutagenesis in mice depends both on the careful design of conditional alleles and on reliable detection of cre gene expression. These procedures include PCR, immunohistochemistry and the use of a recombination-proficient GFP-tagged Cre protein.

Animals↗
PubMed2000

Determination of transport kinetics of chick MCT3 monocarboxylate transporter from retinal pigment epithelium by expression in genetically modified yeast.

Monocarboxylate transporters (MCTs) comprise a group of highly homologous proteins that reside in the plasma membrane of almost all cells and which mediate the 1:1 electroneutral transport of a proton and a lactate ion. The isoform MCT3 is restricted to the basal membrane of the retinal pigment epithelium where it regulates lactate levels in the neural retina. Kinetic analysis of this transporter poses formidable difficulties due to the presence of multiple lactate transporters and their complex interaction with MCTs in adjacent cells. To circumvent these problems, we expressed both the MCT3 gene and a green fluorescent protein-tagged MCT3 construct in Saccharomyces cerevisiae. Since L-lactate metabolism in yeast depends on the CYB2 gene, we disrupted CYB2 to study the MCT3 transporter activity free from the complications of metabolism. Under these conditions L-lactate uptake varied inversely with pH, greater uptake being associated with lower pH. Whereas the V(max) was invariant, the K(m) increased severalfold as the pH rose from 6 to 8. In addition, MCT3 was highly resistant to a number of "classical" inhibitors of lactate transport. Last, studies with diethyl pyrocarbonate and p-chloromercuribenzenesulfonate set limitations on the locus of potential residues involved in the critical site of lactate translocation.

4-Chloromercuribenzenesulfonate↗
PubMed2000

Organization of the mouse ASGR1 gene encoding the major subunit of the hepatic asialoglycoprotein receptor.

The hepatic asialoglycoprotein receptor was the first of the mammalian lectins to be recognized and has been the subject of intense investigation for three decades. Yet, the precise biological role of this major hepatic endocytic receptor has remained elusive. We describe here the characterization of the mouse gene for the major subunit of this receptor (ASGR1) along with 3.5 kb of the upstream 5' region. The gene comprises eight coding exons, with the major transcript in liver displaying a single non-coding 5' exon. A minor hepatic transcript initiates 435 bp upstream of the major start and includes an additional 5' non-coding exon and intron. A minimal 600 bp proximal region of ASGR1 exhibits hepatic-specific promoter activity in HepG2 cells in vitro. These results provide the basis for more detailed genetic studies on the functional role of the hepatic asialoglycoprotein receptor in mammals.

Animals↗