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Biomedical subjects

S Müller

Publications and source records attributed to S Müller.

At least 289 records · Page 16Linked to original sources

Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy.

We have investigated the level of TCR occupancy required to elicit different biological responses in human CTL clones specific for an influenza matrix peptide. Specific cytotoxicity could be detected at extremely low peptide concentrations (10(-12) to 10(-15) M). However, IFN-gamma production, responsiveness to IL-2 and Ca++ fluxes were observed only at peptide concentrations > 10(-9) M, while autonomous proliferation required even higher peptide concentrations. In parallel experiments we measured TCR downregulation to estimate the number of TCRs triggered. We observed that at low peptide concentrations, where only cytotoxicity is triggered, TCR downregulation was hardly detectable. Conversely, induction of IFN-gamma production and proliferation required triggering of at least 20-50% of TCRs. Taken together these results indicate that a single CTL can graduate different biological responses as a function of antigen concentration and that killing of the specific target does not necessarily result in full activation.

Calcium↗

A two-hybrid system analysis shows interactions between 6-phosphofructo-1-kinase and 6-phosphofructo-2-kinase but not between other glycolytic enzymes of the yeast Saccharomyces cerevisiae.

The yeast two-hybrid system was used to investigate whether protein-protein interactions between enzymes of the early reactions of glycolysis exist in the yeast Saccharomyces cerevisiae. Various glycolytic enzymes were fused either to the GAL4 transcription-activating or DNA-binding domain and were tested for their ability to restore GAL4-dependent gene activation. All the different fusion proteins complemented the growth and enzymatic defects caused by the deletion of the respective genes, which indicates that these proteins are still functional. Interactions between the two phosphofructo-1-kinase subunits PFK1 and PFK2, interactions between the phosphofructo-2-kinase subunits, and dimerization of phosphoglucose isomerase were demonstrated. Dimerization of hexokinase 2, however, could not be demonstrated neither with N-terminal nor C-terminal fusions. A direct interaction between the hexose-6-phosphate interconverting enzymes hexokinase 2, phosphoglucose isomerase, and phosphofructo-1-kinase could also not be demonstrated. Nevertheless, our results indicate a weak interaction between phosphofructo-1-kinase and phosphofructo-2-kinase.

Base Sequence↗

Signal extinction and T cell repolarization in T helper cell-antigen-presenting cell conjugates.

We have previously demonstrated that in T cell-antigen-presenting cell (APC) conjugates many T cell receptors (TCR) are serially triggered by a few peptide-MHC complexes, resulting in sustained signaling. Here, we investigate the mechanisms that determine the duration and extent of signaling. We show that in the course of the T helper cell-APC interaction, down-regulation of triggered TCR leads to extinction of signaling. However, T cells that have been activated by a previous encounter with peptide-pulsed APC and have extinguished signaling can swiftly repolarize towards APC displaying higher antigen concentrations and dedicate their help to these cells. These results demonstrate that TCR down-regulation allows T cells to calibrate their response and dedicate their help to APC offering the highest stimulus.

Amino Acid Sequence↗

Brain representation of active and passive movements.

During active and passive (driven by a torque motor) flexion and extension of the right elbow, regional cerebral blood flow (rCBF) was measured in six healthy, male volunteers using positron emission tomography and the standard H2(15)O injection technique. During active as well as during passive movements of the right elbow there were strong increases in rCBF, identical in location, amount, and extent in the contralateral sensorimotor cortex. There were activations during both conditions in the supplementary motor area (stronger and more inferior in the active condition) and inferior parietal cortex (on the convexity during active movements and in the depth of the central sulcus during passive movements). During active movements only, activations of the basal ganglia and the cingulate gyrus were found. Brain activations during motor tasks are largely related to the processing of afferent information.

Adult↗

[Progressive pneumoperitoneum in treatment of inguinal and scar hernias. Results of animal experiments and clinical applications].

Preoperative progressive pneumoperitoneum is a well-known, but sporadically used procedure in preparing patients with giant inguinal or incisional hernias for the operation. The technique requires frequent insufflation of air into the abdominal cavity in order to create space to accommodate herniated viscera and facilitate fascial repair with minimal tension. This article demonstrates the histological findings, technique, complications, advantages and long-term results of the preoperative progressive pneumoperitoneum in hernia repair.

Abdominal Muscles↗

Comparative fluorescence in situ hybridization mapping of primate chromosomes with Alu polymerase chain reaction generated probes from human/rodent somatic cell hybrids.

We have used Alu polymerase chain reaction generated probes from rearranged human/rodent somatic cell hybrids for fluorescence in situ hybridization and comparative mapping of some intrachromosomal changes in the karyotypes of great apes (Pan troglodytes, P. paniscus, Gorilla gorilla, Pongo pygmaeus), a gibbon (Hylobates lar), and an Old World monkey (Macaca fuscata). Probes containing chromosomes 2 and 18 fragments confirmed inversions already suggested by the banding pattern of great ape homologues. However, a chromosome 3 fragment showed complex rearrangements in the gibbon and macaque karyotype which were previously not well defined from banding. 'Subchromosomal painting' will allow the identification of intrachromosomal changes on the basis of DNA homology and provides a powerful method to study karyological and genomic evolution.

Animals↗

Effects of yohimbine on sexual experiences and nocturnal penile tumescence and rigidity in erectile dysfunction.

The therapeutic effect of the alpha 2-antagonist yohimbine in erectile dysfunction was studied in a double-blind placebo-controlled design. Thirty-one male patients underwent extensive clinical, urological, and psychiatric diagnosis and were dichotomically classified into an organic and a nonorganic subgroup. Following a 1-week placebo run-in period, patients were randomly assigned to a placebo or a verum group (yohimbine 15 mg daily) for a treatment period of 7 weeks. The Clinical Global Impression (CGI) scale was used as the primary efficacy parameter. Additionally, nocturnal penile tumescence and rigidity (NPTR) were measured. Global assessment of erectile function applying the CGI scale revealed, beyond a placebo effect in both organic and nonorganic patients, a therapeutic effect in the subgroup of nonorganic patients, with a significantly greater improvement in the yohimbine group compared to the placebo group. No superiority of yohimbine compared to placebo was found in the organic patients. These findings on the subjective level had no correlate in the NPTR recordings. The NPTR parameters were unchanged under yohimbine treatment in both the nonorganic and organic subgroup. No interrelation was found between subjective improvement and NPTR alterations. Polysomnographic control of the NPTR registrations ensured that the duration of REM sleep under treatment was not influenced.

Adult↗

Metabolism of dynorphin A1-13 in human CSF.

In-vitro incubation of human cerebrospinal fluid (CSF) obtained from patients ranging from 22-78 years with 10 microM of dynorphin A1-13 (Dyn A1-13) resulted in several cleavage products. Dyn A1-12 and A2-13 were identified as the major CSF metabolites by matrix-assisted laser desorption mass spectrometry (LD-MS). Further metabolites were Dyn A1-6, A2-12 and A4-12. LD-MS further suggested the formation of Dyn A1-8, A1-7, A1-10, A7-10, A3-12, A7-12, A3-13, A7-13 and A8-13. The metabolic half-life of Dyn A1-13 at 37 degrees C was approximately 2.5 h (range 1.75-8.5 h), compared to less than one minute in plasma. The half-life of Dyn A1-13 decreased markedly with age or age-associated processes (n = 20, r2 = 0.498). Noncompartmental kinetic analysis in the absence or presence of enzyme inhibitors (leucinethiol 10 microM, captopril 100 microM and GEMSA 20 microM) suggested that Dyn A1-13 is mainly metabolized by carboxypeptidase to A1-12 (51%) and by aminopeptidases to A2-13 (35%). The generation of A1-6 (13%) was only detected under enzyme inhibition. The extent of conversion into the main metabolites did not follow an age-associated trend, thus over-all enzyme levels but no specific enzymatic systems are elevated with age.

Adult↗

Effect of haloallylamines on polyamine oxidase activity and spermine levels in Ascaris suum.

In parasitic nematodes the rate-limiting step in the polyamine interconversion pathway is catalysed by polyamine oxidase. MDL 72527, the specific inhibitor of mammalian polyamine oxidase, had no effect on the Ascaris suum enzyme, whereas its activity was inhibited in a time-dependent manner by the haloallylamine MDL 72145, originally designed as a specific inhibitor of monoamine oxidase A and B. The dissociation constant (Ki) was found to be 0.9 microM and the enzyme half-life under saturation conditions (t50) was determined to be 0.8 min. Incubation of A. suum in vitro in the presence of 50 microM MDL 72145 for 6 h resulted in a decrease in polyamine oxidase activity to about 20% of the control value, and spermine concentrations simultaneously increased about 200%. Both results suggest that MDL 72145 might be a chemical lead compound for the design of new chemotherapeutic agents against nematode infections.

Allylamine↗

Preoperative two- and three-dimensional transesophageal echocardiographic assessment of heart tumors.

BACKGROUND: Two-dimensional transesophageal echocardiography is the most widely used diagnostic approach in the rare entity of heart tumors. The aim of this study was to assess the diagnostic usefulness of three-dimensional echocardiography in comparison with the two-dimensional technique in a rare clinical setting. METHODS: Twenty-seven patients (18 women; mean age, 49.7 +/- 14 years) with a histologically proven diagnosis of a cardiac tumor were studied. The primary diagnosis was done by a two-dimensional transthoracic echocardiography (n = 9) and transesophageal echocardiography (n = 18). In addition, we performed three-dimensional transesophageal assessment in 5 patients with left atrial myxomas. The echocardiographic findings were compared with the intraoperative appearance and pathologic diagnosis. RESULTS: The echocardiographically suspected diagnosis of a heart tumor in 29 cases was histologically correct in 27 patients (myxomas, 20; epicardial lipoma, 1; malignant epicardial mesothelioma, 1; metastatic processes of hypernephromas, 2; and undifferentiated tumors of the pericardium, 3). Only the combination of multiplane transesophageal and three-dimensional echocardiography was able to demonstrate the shape, dimensions, location, origin, surface, three-dimensional movement, and involvement of valves and was most useful in the preoperative diagnosis and planning. CONCLUSIONS: Three-dimensional transesophageal echocardiography yields important additional clinical information and improves the operative planning. Three-dimensional echocardiography may become the best approach to study the anatomy and pathology of the heart as it provides an objective display of cardiac size and shape in heart tumors.

Adult↗

Occurrence of nitro and non-nitro benzenoid musk compounds in human adipose tissue.

Nitro benzenoid musk compounds (Musk tibetene [CAS no. 145-39-1], Musk ambrette [83-66-9], Musk moskene [116-66-5], Musk ketone [81-14-1] and Musk xylene [81-15-2]) and non-nitro benzenoid musks (Celestolide [13171-00-1], Galaxolide [1222-05-5]) and Fixolide [1506-02-1] [21445-77-7] were analysed in 15 human adipose tissue samples from Switzerland by gas chromatography/high resolution mass spectrometry. The levels of Musk xylene and Galaxolide ranged up to 288 ng/g lipids and 171 ng/g lipids, respectively. The concentrations of non-nitro benzenoid musks found in human adipose tissue raise concern since very few toxicological data are available.

Adipose Tissue↗

Multiplane transoesophageal echocardiography is the only definitive ultrasound approach in adult supravalvular aortic stenosis.

This report describes a rare case of isolated supravalvular aortic stenosis (SVAS) in a 28 year-old female patient. A congenital heart defect, diagnosed at birth, was until 1994 suspected to be a valvular aortic stenosis (VAS). Cardiac catheterization led to the diagnosis of supravalvular aortic stenosis, which could easily be confirmed by multiplane but not by monoplane transoesophageal echocardiography (TEE). Precordial examinations had not revealed the vitium, probably because the SVAS is a rare malformation of the ascending aorta, but with multiplane TEE the aortic narrowing could be imaged clearly and pressure gradients comparable to those found with invasive measurements were established. The advantage of this non-invasive method for diagnosis and preoperative preparation are discussed in detail.

Adult↗

Tetraamido-substituted 2,3-naphthalocyanine zinc(II) complexes as phototherapeutic agents: synthesis, comparative photochemical and photobiological studies.

The aim of this study is to report the synthesis and photochemical and phototherapeutic activities of tetraamido-substituted 2,3-naphthalocyanine zinc(II) complexes (ZnNcs 5-8). Four naphthalocyanine complexes, tetrabenzamido- (ZnNc 5), tetramethoxybenzamido- (ZnNc 6), tetrahexylamido- (ZnNc 7) and tetradodecylamido- (ZnNc 8) naphthalocyanine zinc complexes absorbing at around 770 nm were synthesized. The dye-sensitized photo-oxidation of 1,3-diphenylisobenzofuran via 1O2 was studied in more detail in order to compare the quantum yields of these different sensitizers. Pharmacokinetic and photodynamic therapy studies of Lewis lung carcinoma in mice were carried out after administration of liposome incorporated ZnNcs 5-8. The phototherapeutic efficiency was evaluated by changes in the mean tumour diameter with time, regrowth delay (days), average survival time (days) and electron microscopy observations. According to all assessment criteria used, the most promising photosensitizer seems to be tetrabenzamido-substituted ZnNc 5. We suggest that mainly structural properties are the reason for the better results observed. The morphological analysis confirms the mechanism of photonecrosis, which was observed in our previous work with unsubstituted and substituted ZnNcs 1-4. Direct photodamage to the membrane, mitochondria and rough endoplasmic reticulum in the neoplastic cells and delayed photodestruction of the endothelial cells surrounding the tumour tissue were detected. Also, changes in lysosomes were observed. The data presented through different parameters are compared with such obtained for other photodynamic therapy sensitizers.

Animals↗

Filensin and phakinin form a novel type of beaded intermediate filaments and coassemble de novo in cultured cells.

The fiber cells of the eye lens possess a unique cytoskeletal system known as the "beaded-chain filaments" (BFs). BFs consist of filensin and phakinin, two recently characterized intermediate filament (IF) proteins. To examine the organization and the assembly of these heteropolymeric IFs, we have performed a series of in vitro polymerization studies and transfection experiments. Filaments assembled from purified filensin and phakinin exhibit the characteristic 19-21-nm periodicity seen in many types of IFs upon low angle rotary shadowing. However, quantitative mass-per-length (MPL) measurements indicate that filensin/phakinin filaments comprise two distinct and dissociable components: a core filament and a peripheral filament moiety. Consistent with a nonuniform organization, visualization of unfixed and unstained specimens by scanning transmission electron microscopy (STEM) reveals the the existence of a central filament which is decorated by regularly spaced 12-15-nm-diam beads. Our data suggest that the filamentous core is composed of phakinin, which exhibits a tendency to self-assemble into filament bundles, whereas the beads contain filensin/phakinin hetero-oligomers. Filensin and phakinin copolymerize and form filamentous structures when expressed transiently in cultured cells. Experiments in IF-free SW13 cells reveal that coassembly of the lens-specific proteins in vivo does not require a preexisting IF system. In epithelial MCF-7 cells de novo forming filaments appear to grow from distinct foci and organize as thick, fibrous laminae which line the plasma membrane and the nuclear envelope. However, filament assembly in CHO and SV40-transformed lens-epithelial cells (both of which are fibroblast-like) yields radial networks which codistribute with the endogenous vimentin IFs. These observations document that the filaments formed by lens-specific IF proteins are structurally distinct from ordinary cytoplasmic IFs. Furthermore, the results suggest that the spatial arrangement of filensin/phakinin filaments in vivo is subject to regulation by host-specific factors. These factors may involve cytoskeletal networks (e.g., vimentin IFs) and/or specific sites associated with the cellular membranes.

Animals↗