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S Müller

Publications and source records attributed to S Müller.

At least 199 records · Page 11Linked to original sources
PubMed1999

ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft recipients.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to slow the progression of chronic renal failure. However, the value of ACE inhibitors for the treatment of hypertension in renal allograft recipients has not been established. ACE inhibitors dilate the efferent glomerular arteriole, an effect that may aggravate the decrease in glomerular filtration rate resulting from cyclosporine-induced vasoconstriction at the afferent glomerular arteriole. Therefore, the goal of this double-blind, randomized study was to compare the antihypertensive and renal effects of the ACE inhibitor quinapril with those of the beta-blocker atenolol in renal allograft recipients in whom hypertension developed 6 to 12 weeks after transplantation. All patients received cyclosporine as an immunosuppressant and had stable graft function (serum creatinine concentration, <220 micromol/L) at entry into the study. Twenty-nine patients who received quinapril (daily dose titrated between 2.5 and 20 mg) and 30 patients who received atenolol (daily dose titrated between 12.5 and 100 mg) completed the 24-month study. The two groups did not differ in age, sex ratio, height, and weight before entry into the study. Quinapril decreased diastolic blood pressure from 96+/-1 to 84+/-1 mm Hg (average throughout treatment period), and atenolol decreased diastolic blood pressure from 96+/-1 to 83+/-1 mm Hg. The serum creatinine concentration did not change significantly in either group after 24 months (129+/-8 micromol/L at entry and 148+/-19 micromol/L after 24 months in the quinapril group and 131+/-6 micromol/L at entry and 152+/-15 micromol/L after 24 months in the atenolol group; P=NS for both groups). After 24 months, the change in urinary albumin excretion from baseline was -10+/-15 mg/d in the quinapril group and 52+/-32 mg/d in the atenolol group (P=0.03). These results show that quinapril and atenolol are effective antihypertensive drugs when used after renal transplantation. Moreover, compared with atenolol, quinapril has no adverse effects on graft function. The relative reduction in albuminuria observed with quinapril as compared with atenolol could indicate a beneficial effect of quinapril on long-term graft function.

Adolescent↗
PubMed1999

Reorganization of sensory and motor systems in hemiplegic stroke patients. A positron emission tomography study.

BACKGROUND AND PURPOSE: Cortical reorganization of motor systems has been found in recovered stroke patients. Reorganization in nonrecovered hemiplegic stroke patients early after stroke, however, is less well described. We used positron emission tomography to study the functional reorganization of motor and sensory systems in hemiplegic stroke patients before motor recovery. METHODS: Regional cerebral blood flow (rCBF) was measured in 6 hemiplegic stroke patients with a single, subcortical infarct and 3 normal subjects with the [(15)O]H(2)O injection technique. Brain activation was achieved by passive elbow movements driven by a torque motor. Increases of rCBF comparing passive movements and rest were assessed with statistical parametric mapping. Significant differences were defined at P<0.01. RESULTS: In normal subjects, significant increases of rCBF were found in the contralateral sensorimotor cortex, supplementary motor area, cingulate cortex, and bilaterally in the inferior parietal cortex. In stroke patients, significant activation was observed bilaterally in the inferior parietal cortex and in the contralateral sensorimotor cortex, ipsilateral prefrontal cortex, supplementary motor area, and cingulate cortex. Significantly larger increases of rCBF in patients compared with normal subjects were found bilaterally in the sensorimotor cortex, stronger in the ipsilateral, unaffected hemisphere, and in both parietal lobes, including the ipsilateral precuneus. CONCLUSIONS: Passive movements in hemiplegic stroke patients before clinical recovery elicit some of the brain activation patterns that have been described during active movements after substantial motor recovery. Changes of cerebral activation in sensory and motor systems occur early after stroke and may be a first step toward restoration of motor function after stroke.

Aged↗
PubMed1999

Clinically relevant cholesterol elevation in anxiety disorders: a comparison with normal controls.

Recently, several studies reported elevated cholesterol levels in panic disorder, agoraphobia, and general anxiety disorder, but the clinical relevance is still unsettled. All studies so far have disregarded the possible influence of dietary and physical exercise factors. In this study, 30 patients with different anxiety disorders and 30 normal controls were compared for total cholesterol, low-density lipoprotein (LDL), and cholesterol high-density lipoprotein (HDL) ratio. Dietary and physical exercise habits were measured by self-rating questionnaires. Patients with anxiety disorders had significantly elevated total cholesterol, LDL, and cholesterol/HDL ratios. Patients showed borderline-high or high cholesterol levels almost 3 times as often as control participants. Anxiety-specific avoidance of physical exercise and special dietary habits of anxiety patients had a significant but minor impact on differences in cholesterol between both groups. Our data support the assumption that serum cholesterol elevations in anxiety disorder patients are within a clinically relevant range.

Journal Article↗
PubMed1999

Nonradioactive labeling of large DNA fragments for genome walking, RFLP and northern blot analysis.

In this report, we present a simple nonradioactive labeling procedure for DNA fragments of high specific labeling density that can be used for a variety of applications. The protocol is based on the universal mono-functional platinum reagent for chemical digoxigenin (DIG) labeling of nucleic acids. The labeling protocol was optimized for large DNA templates as complete bacterial artificial chromosomes (BAC). Variations of incubation time and temperature improved the labeling density such that about 30% of the nucleotides were DIG-modified within 30 min. Furthermore, the refined procedure generates in a single-tube reaction and without prior digestion-labeled DNA fragments of 0.5-4.0 kb from a 130-kb template. Hybridization experiments were performed on Southern and northern blots and allowed the detection of single copy genes in 2.5 micrograms genomic DNA from Arabidopsis thaliana, which has a haploid genome size of 0.13 pg (ca. 120 Mb) and medium expressed transcripts from 0.8 microgram poly(A)+ RNA, respectively. The extremely high specific labeling density, the stability and the universal application of the probe generated with the platinum reagent makes this method a useful alternative to classical radioactive nuclei acids labeling techniques.

Alleles↗
PubMed1999

Simultaneous MALT-type lymphoma and early adenocarcinoma of the stomach associated with Helicobacter pylori gastritis.

We report about two cases of combined gastric lymphoma and gastric carcinoma with one of them representing a case of early gastric high grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) with co-existing early gastric adenocarcinoma. In contrast to most previously reported similar cases, in both of our cases the definitive diagnosis of gastric lymphoma and carcinoma was obtained preoperatively. This, however, seems to be in future times an essential prerequisite for employing minimal invasive methods such as eradication therapy in the case of diagnosed early lymphoma and endoscopic treatment for early gastric carcinomas. These methods have been proven to be an effective and beneficial alternative treatment especially with regard to the life quality of the patients.

Adenocarcinoma↗
PubMed1999

[Xenotransplantation. Possibilities of animal breeding].

The pig is the most likely donor organism for xenotransplantation of organs to humans. However, since this constellation is discordant, hyperacute rejection needs to be overcome. This review summarises current strategies of genetically modifying pigs for xenotransplantation. Limitations of the classical method of DNA-microinjection and new perspectives arising from the possibility of cloning animals from cultured cells are discussed.

Animals↗
PubMed1998

Trivalent antimonials induce degradation of the PML-RAR oncoprotein and reorganization of the promyelocytic leukemia nuclear bodies in acute promyelocytic leukemia NB4 cells.

Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17) chromosomal translocation that fuses the genes encoding the promyelocytic leukemia protein (PML) and the retinoic acid receptor (RAR). The resulting PML-RAR protein induces a block in the differentiation of the myeloid progenitor cells, which can be released by retinoic acid (RA) in vitro and in vivo. The RA-induced differentiation of APL blasts is paralleled by the degradation of the fusion protein and the relocation of wild-type PML from aberrant nuclear structures to its normal localization in nuclear bodies. Recently, arsenic trioxide (As2O3) treatment was proposed as an alternative therapy in APL, because it can induce complete remission in both RA-sensitive and -resistant APL patients. Intriguingly, As2O3 was also shown to induce degradation of the PML-RAR chimera and to reorganize PML nuclear bodies. Here we show that trivalent antimonials also have striking effects on RA-sensitive and RA-resistant APL cells. Treatment of the APL-derived NB4 cells and the RA-resistant subclone NB4R4 with antimony trioxide or potassium antimonyl tartrat triggers the degradation of the fusion protein and the concomitant reorganization of the PML nuclear bodies. In addition, as reported for As2O3, the antimonials provoke apoptosis of NB4 and NB4R4 cells. The mechanism of antimony action is likely to be similar to that of As2O3, notably both substances induce the attachment of the ubiquitin-like SUMO-1 molecule to the PML moiety of PML-RAR. From these data, we propose that, in analogy to As2O3, antimonials might have a beneficial therapeutic effect on APL patients, perhaps with less toxicity than arsenic.

Antimony↗
PubMed1998

Cross-species colour segmenting: a novel tool in human karyotype analysis.

We used fluorescence in situ hybridization (FISH) with DNA probes derived from bivariate fluorescence activated flow sorting of primate chromosomes. In cases where human and primate karyotypes differ by chromosome rearrangements, reverse painting of primate probes resulted in a subregional delineation of the human homologous chromosomes. Probes were used from two gibbon species (Hylobates concolor and H. syndactylus) which both showed highly rearranged karyotypes. Hybridization of human chromosomes with painting probes derived from both gibbons showed that, with the exception of human chromosomes 15, 18, 21, 22 and the sex chromosomes, each chromosome was differentiated in at least two and up to six segments. These probes have been used in the analysis of various cases of constitutional chromosomal rearrangements in human pathology including complex intrachromosomal rearrangements. They were also used in a multi colour format (colour segmenting) to differentiate the entire human karyotype into 81 homologous coloured segments with probes derived from H. concolor, and 74 segments with probes derived from H. syndactylus. The addition of colours not only simplifies chromosome identification compared to the analysis of classical banding based on grey values, but colour segmenting also provides simple coloured landmarks for further fine analysis by classical banding.

Animals↗
PubMed1998

A supraspliceosome model for large nuclear ribonucleoprotein particles based on mass determinations by scanning transmission electron microscopy.

Pre-mRNA splicing is an important regulatory step in the expression of most eukaryotic genes. In vitro studies have shown splicing to occur within 50-60 S multi-component ribonucleoprotein (RNP) complexes termed spliceosomes. Studies of mammalian cell nuclei have revealed larger complexes that sediment at 200 S in sucrose gradients, termed large nuclear RNP (lnRNP) particles. These particles contain all factors required for pre-mRNA splicing, including the spliceosomal U snRNPs and protein splicing factors. Electron microscopy has shown them to consist of four apparently similar substructures. In this study, mass measurements by scanning transmission electron microscopy of freeze-dried mammalian lnRNP preparations, both confirm the similarity between the lnRNP particles and reveal the mass uniformity of their subunits. Thus, the tetrameric lnRNP particle has a mass of 21.1(+/-1.6) MDa, while each repeating subunit has a mass of 4.8(+/-0.5) MDa, which is close to the estimated mass of the fully assembled 60 S spliceosome. The 1.9 MDa discrepancy between the lnRNP particle's mass and the cumulative masses of its four subunits may be attributed to an additional domain frequently observed in the micrographs. Notably, strands and loops of RNA were often seen emanating from lnRNP particles positively stained with uranyl formate. Our results support the idea that the nuclear splicing machine is a supraspliceosome complex. For clarity, we define spliceosomes devoid of pre-mRNA as spliceosome cores, and propose that the supraspliceosome is constructed from one pre-mRNA, four spliceosome cores, each composed mainly of U snRNPs, and additional proteins. In this way a frame is provided to juxtapose exons about to be spliced.

Mass Spectrometry↗
PubMed1998

[Basalioma].

Explore the source record for details and available documents.

Basal Cell Carcinoma↗
PubMed1998

Characterization of KIF1C, a new kinesin-like protein involved in vesicle transport from the Golgi apparatus to the endoplasmic reticulum.

Kinesins comprise a large family of microtubule-based motor proteins, of which individual members mediate specific types of motile processes. Using the ezrin domain of the protein-tyrosine phosphatase PTPD1 as a bait in a yeast two-hybrid screen, we identified a new kinesin-like protein, KIF1C. KIF1C represents a member of the Unc104 subfamily of kinesin-like proteins that are involved in the transport of mitochondria or synaptic vesicles in axons. Like its homologues, the 1103-amino acid protein KIF1C consists of an amino-terminal motor domain followed by a U104 domain and probably binds to target membranes through carboxyl-terminal sequences. Interestingly, KIF1C was tyrosine-phosphorylated after peroxovanadate stimulation when overexpressed in 293 or NIH3T3 fibroblasts or in native C2C12 cells. Using immunofluorescence, we found that KIF1C is localized primarily at the Golgi apparatus. In brefeldin A-treated cells, the Golgi membranes and KIF1C redistributed to the endoplasmic reticulum (ER). This brefeldin A-induced flow of Golgi membranes into the ER was inhibited in cells transiently overexpressing catalytically inactive KIF1C. In conclusion, our data suggest an involvement of tyrosine phosphorylation in the regulation of the Golgi to ER membrane flow and describe a new kinesin-like motor protein responsible for this transport.

Amino Acid Sequence↗
PubMed1998

Enhanced binding of antibodies to the DTR motif of MUC1 tandem repeat peptide is mediated by site-specific glycosylation.

The epithelial mucin MUC1 is an important tumor marker of breast cancer and other carcinomas. Its immunodominant DTR motif, which is the principal target for immunotherapeutic approaches, has been assumed until recently not to be glycosylated in both normal and tumor MUC1 and to acquire its immunogenic conformation by virtue of a certain number of tandem repeats. We present evidence that the antigenicity of the single repeat toward a considerable number of antibodies to the DTR motif is greatly enhanced if it is glycosylated within this motif, and only in this position. Twenty-eight monoclonal anti-MUC1 antibodies with DTR specificity were tested for binding to synthetic 21-mer (AHG21) or 20-mer (HGV20) tandem repeat peptides O-glycosylated with galactose beta1-3N-acetylgalactosamine alpha or N-acetylgalactosamine alpha at defined Thr or Ser positions. Binding was measured in ELISA experiments using the glycopeptides as plate-immobilized antigens or as inhibitors in solution. At least 12 antibodies revealed significantly enhanced binding to the peptides glycosylated at the DTR motif (Thr-10) as compared to positional isomers glycosylated at Thr-5, Ser-6, Ser-16, or Thr-17 and to the nonglycosylated peptides. Six antibodies (VU-3-C6, A76-A/C7, Ma552, VU-11-D1, VU-12-E1, and VU-11-E2) that were unreactive with the monomeric repeat peptide did bind to the DTR-glycosylated peptide. Several lines of evidence suggest that glycosylation with N-acetylgalactosamine is sufficient for the observed enhancement effect. Our results are of special interest in conjunction with the recent observation that the DTR motif of lactation-associated MUC1 is O-glycosylated in vivo (Müller et al., J. Biol. Chem., 272: 24780-24793, 1997). They may have consequences for the design of efficient tumor vaccines.

Antibodies, Monoclonal↗
PubMed1998

Long-term immune reconstitution and outcome after HLA-nonidentical T-cell-depleted bone marrow transplantation for severe combined immunodeficiency: a European retrospective study of 116 patients.

We have performed a retrospective analysis of the development of T- and B-cell functions after HLA-nonidentical T-cell-depleted bone marrow transplantation (BMT) performed in 193 patients with severe combined immunodeficiency (SCID) at 18 European centers between December 1982 and December 31, 1993. One hundred sixteen of 193 patients were alive with evidence of engraftment 6 months after BMT. Development of T-cell function occurred earlier than B-cell function and was achieved more frequently up to the time of last follow-up. The median time to achieve normal T-cell function was 8.7 months, whereas the median time to achieve normal B-cell function was 14.9 months. Twenty-four patients died later than 6 months post-BMT, mainly due to chronic graft-versus-host disease (cGVHD) and/or viral infection. Absence of T-cell reconstitution 6 months after BMT, unlike absence of B-cell reconstitution, was associated with a poor outcome. Two additional factors were associated with a poor outcome: presence of cGVHD 6 months after BMT and B- SCID versus B+ SCID. However, two of these three factors remained as significant prognostic factors in a multivariate analysis: the absence of T-cell function and the presence of cGVHD 6 months after BMT. Analysis of the factors influencing the development of immune reconstitution showed that T- and B-cell functions occurred earlier and more frequently in B+ SCID versus B- SCID patients. Acute GVHD was associated with a slower development of T-cell function at 6 months, and cGVHD had a negative influence on the development of T-cell function afterwards, but neither acute nor chronic GVHD was found to influence the development of B-cell function. Once engraftment occurred, whether patients had or had not received Busulfan in the conditioning regimen did not influence the kinetics and quality of T-cell function development. In a multivariate study, two factors were found to influence the T-cell function 6 months after BMT: type of SCID and acute GVHD. The results of this retrospective analysis should lead to new protocols adapted to SCID disease, considering that disease-related as well as BMT-related parameters influence the development of immune function and thereby long-term outcome after HLA-nonidentical T-cell-depleted BMT.

B-Lymphocytes↗
PubMed1998

The role of the C-terminus for catalysis of the large thioredoxin reductase from Plasmodium falciparum.

The thioredoxin system is one of the major thiol reducing systems of the cell. Recent studies have revealed that Plasmodium falciparum and human thioredoxin reductase represent a novel class of enzymes, which are substantially different from the isofunctional prokaryotic Escherichia coli enzyme. We identified the cysteines Cys88 and Cys93 as the redox active disulfide and His509 as the active site base [Gilberger, T.-W., Walter, R.D. and Müller, S., J. Biol. Chem. 272 (1997) 29584-29589]. In addition to the active site thiols Cys88 and Cys93 the P. falciparum enzyme has another pair of cysteines at the C-terminus: Cys535 and Cys540. To assess the possible role of these peripheral cysteines in the catalytic process the single mutants PfTrxRC535A and PfTrxRC540A, the double mutant P/TrxRC535AC540A and the deletion mutant PfTrxRdelta9 (C-terminal deletion of the last nine amino acids) were constructed. All mutants are defective in their thioredoxin reduction activity, although they still show reactivity with 5,5'-dithiobis (2-nitrobenzoate). These data imply that the C-terminal cysteines are crucially involved in substrate coordination and/or electron transfer during reduction of the peptide substrate.

Animals↗
PubMed1998

Noninvasive biomagnetic imaging in coronary artery disease based on individual current density maps of the heart.

OBJECTIVE: In this paper we present an attempt at noninvasive imaging of distributed myocardial electrical activity in patients suffering from myocardial infarction and in healthy subjects. Although advances have been made, noninvasive three-dimensional imaging of cardiac electrophysiological activity is still in its infancy and extending our knowledge of cardiac electrophysiological properties may be a valuable guide in the treatment of patients with coronary artery disease. METHODS: Magnetic field mapping data formed the input for an inverse solution that is based on a multiple dipole model. The lead field normalized minimum norm least square criterion was applied to predefined myocardial source geometry. Current density distributions were calculated for the left ventricle during ventricular depolarization. Images from two patients with previous myocardial infarction were compared to images from two healthy subjects. RESULTS: Low regional and global current density was found in the infarction patients. Regions of low current density corresponded to infarcted segments. The images of the healthy subjects displayed less marked areas of low current density. CONCLUSION: The proposed multiple dipole model may be able to distinguish viable from scarred myocardium. A prospective clinical study should be undertaken to investigate the spatial resolution and the diagnostic performance of this method.

Body Surface Potential Mapping↗
PubMed1998

Laparoscopic recovery of pronuclear-stage goat embryos.

The oviducts of 16 Saanen does, superovulated with follicle-stimulating hormone (FSH) and synchronised with prostaglandin F2 alpha were flushed 75 to 86 hours after the injection of prostaglandin. The mean (sd) ovulation rate was 13.7 (3.9). The flushings were directed orthograde through a flexible intravenous catheter, which was introduced into the oviduct via the infundibulum. The flushing medium was recovered by a balloon-catheter, which was placed in the uterine lumen near the uterotubal junction. Five does were flushed unilaterally either because they had one blocked oviduct or because they had ovulated on only one ovary. The overall embryo recovery rate was 72 per cent. Nine weeks later 11 of the donor ewes were examined laparoscopically and no adhesions of the reproductive organs were observed. Eight of these does were synchronised with progestagen-vaginal sponges, superovulated with FSH and their oviducts were flushed again. Their mean ovulation rate was 16.0 (4.3) and 86 per cent of the embryos were recovered. The optimal time to obtain pronuclear stage embryos was 75 to 78 hours after the injection of prostaglandin. All the embryos recovered within this period were at the pronuclear stage whereas 28 per cent of those recovered one to six hours later were at the two- or four-cell stage.

Animals↗