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Biomedical subjects

T Müller

Publications and source records attributed to T Müller.

At least 19 recordsLinked to original sources
PubMed1992

Levitation, holding, and rotation of cells within traps made by high-frequency fields.

Biological cells and other particles can be electrically manipulated by means of negative dielectrophoresis within microchambers whose electrode geometry is of the order of the cell size. Very-high-frequency fields (50 MHz and above) and media of increased relative permittivity are especially suitable for the purpose, as shown by experimental data on levitation and rotation. It appears to be possible to move and rotate cells or particles at will using this technology.

Cytological Techniques↗
PubMed1992

Calcium entry through kainate receptors and resulting potassium-channel blockade in Bergmann glial cells.

Glutamate receptors, the most abundant excitatory transmitter receptors in the brain, are not restricted to neurons; they have also been detected on glial cells. Bergmann glial cells in mouse cerebellar slices revealed a kainate-type glutamate receptor with a sigmoid current-to-voltage relation, as demonstrated with the patch-clamp technique. Calcium was imaged with fura-2, and a kainate-induced increase in intracellular calcium concentration was observed, which was blocked by the non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and by low concentrations of external calcium, indicating that there was an influx of calcium through the kainate receptor itself. The entry of calcium led to a marked reduction in the resting (passive) potassium conductance of the cell. Purkinje cells, which have glutamatergic synapses, are closely associated with Bergmann glial cells and therefore may provide a functionally important stimulus.

Animals↗
PubMed1992

Classification of oxygen transport to tissue with neural networks.

In the current stage of the development of the EMPHO II it was shown that the transport of oxygen to tissue can be classified for all applications in real time by using neural networks. The resolution of the oxygen classification is 1%. The implementation of the neural network is possible on a commercial signal processor TMS 320C30 board which is compatible with an IBM PC. The implementation of the neural network is done fully in software and no special neurocomputer is necessary. The results are very promising so that the neural network design goals will be established in the future. In the future further efforts will be made in order to increase the data base and to train the network in more detail.

Animals↗
PubMed1992

5-HT1A receptor-effector system responsivity in panic disorder.

To explore 5-HT1A receptor responsivity in panic disorder (PD), hypothermic, neuroendocrine and behavioral responses to the selective partial 5-HT1A receptor agonist ipsapirone (IPS) were investigated in patients with primary PD and healthy controls. Fourteen patients and matched controls received a single oral dose of 0.3 mg/kg IPS or placebo under double-blind, random-assignment conditions. IPS induced hypothermia and corticotropin (ACTH)/cortisol release but had only minimal effects on behavior. Compared with controls, the patients with PD exhibited significantly attenuated thermoregulatory and neuroendocrine responses to IPS. Although the healthy subjects reported increased drowsiness and the PD patients rated themselves more nervous and less calm following administration of IPS, no consistent changes in ratings of anxiety or panic symptoms were recorded. The impaired hypothermic and ACTH/cortisol responses following 5-HT1A receptor activation reflects subsensitivity of both the pre- and post-synaptic 5-HT1A receptor-effector system, thus supporting the hypothesis that a 5-HT1A receptor-related serotonergic dysfunction may be linked to the pathophysiology of PD. Future studies of 5-HT1A receptor-effector complex function in conjunction with assessment of the responsivity of other subtypes (e.g. 5-HT2, 5-HT3) should promote the evaluation of 5-HT system integrity in anxiety disorders and its involvement in anxiolytic drug effects.

Adrenocorticotropic Hormone↗
PubMed1992

Hemophan versus hemophan--a philippic against the suggestion of constant membrane quality.

All statements referring to biocompatibility of dialyzers depend on the suggestion of a constant and reproducible structure of the investigated membrane material. The data presented here strike this concepts in case of hemophane. Two commercially available hemophane dialyzers, the GF MC 120 (Gambro) and the MO 450 (SMAD) membranes, were compared. Significant differences could be seen in the induction of leukopenia and leukocyte sequestration reaction within patients lungs, but also in capacity to influence granulocyte oxidative metabolism and release of granular enzymes. According to these data it seems questionable whether hemophane is a membrane material with constant structure and quality normally expected for products bearing trade names. Excluding other differences (like surface-area or sterilization method) variable amounts of DEAE substituents and/or an inconstant distribution of the DEAE groups within the membranes may be the most possible reason responsible for the differences found. The study underlines the urgent need of an exact physico-chemical characterization of dialyzer membranes and is therefore a challenge for free publication of such basic data by the producers.

Biocompatible Materials↗
PubMed1992

p53 mosaicism with an exon 8 germline mutation in the founder of a cancer-prone pedigree.

Changes in the tumor-suppressor gene p53 are frequently acquired during the course of malignant development of human tumors. Recently, constitutional heterozygous mutations in p53 exon 7 have been identified as the primary cause of cancer predisposition in cases of the familial Li-Fraumeni cancer syndrome. These findings underline the need for extensive mutation screening in families with high cancer incidence. This report describes the detection and follow-up by two-dimensional single-strand conformation polymorphism analysis (2DSSCP) of a new germline mutation of p53 exon 8 in a case of suspected Li-Fraumeni syndrome. Although a high cancer incidence had been reported in the family history of the father of siblings suffering from brain tumor and rhabdomyosarcoma, a constitutional heterozygous p53 mutation was identified only in the affected children. Retrospective analysis of archival tissue of a half-sister who died several years ago from a tumor of previously uncertain diagnosis revealed the same mutation. The mutation had therefore occurred in the germ cells of the mother, who thus appears to be a mosaic. The cancer predisposition of the paternal ancestors must have been due to other factors.

Adolescent↗
PubMed1992

Light-microscopic demonstration of methylene blue accumulation sites in mouse brain after supravital staining.

Mouse brains were stained supravitally with methylene blue and studied in paraffin sections by light microscopy. In the perikarya, the dye was found to bind primarily to the nuclei; only slight staining of the cytoplasm was observed. Dye accumulations within nerve fibers were found in the nodes of Ranvier and in the varicosities of the unmyelinated endings. Specific dye binding in dendrites corresponded mainly to beads and spines. The accumulation sites in terminal neuronal processes appeared to be closely related to the plasma membrane. These morphological data would explain the neurophysiologically proven interaction of the dye with calcium-binding sites in membranes.

Animals↗
PubMed1992

[Anti-oxidative therapy of pancreatitis--an 18-month interim evaluation].

99 patients affected with acute pancreatitis of different genesis were treated in hospital (necrotizing n = 38, mild form n = 61) from May 1990 to November 1991. Nearly 80% of these illnesses were ethanol-induced, 12% were of biliary origin. 90 patients were submitted to an adjuvant antioxidant therapy with selenium and D-alpha-tocopherol (necrotizing form n = 29, mild form n = 61). The average lethality rate of 34% (1982-1989) fell to 1.1% (1 female patient with biliarily induced pancreatitis). No lethal courses were observed in alcohol-induced, idiopathic, post-traumatic, and post-operative forms. Clinical courses proceeded more easily under adjuvant antioxidant therapy, surgical treatment was not necessary. A treatment at reasonable costs can be made in all general internal wards.

Acute Disease↗
PubMed1991

Cadmium/zinc-metallothionein induces DNA strand breaks in vitro.

The in vitro DNA strand breaking activity of metallothionein (MT) containing Cd2+ and Zn2+ in a molar ratio of 5:2 is described. Studies with radical scavengers and electron paramagnetic resonance spectroscopy indicate that the DNA damage might be caused by a radical species formed by the native protein (i.e., MT) charged with the heavy metal ions. No DNA strand breaks are detectable with the heat-denatured MT or with Cd2+ or Zn2+ alone. Inhibition studies using EDTA as a metal ion chelator or N-ethylmaleimide to alkylate sulfhydryl groups suggest that both the bound heavy metal ions as well as the SH groups of the various cysteine residues of MT may be involved in the MT-dependent DNA cleavage. Further characterization showed that the DNA cleavage is more likely random than sequence- or base-specific. These observations may provide a clue in the search for initial events in Cd-related carcinogenicity.

Animals↗
PubMed1991

Long-term fluoxetine treatment decreases 5-HT1A receptor responsivity in obsessive-compulsive disorder.

Fluoxetine (FLX) is a selective serotonin (5-HT) reuptake inhibitor with therapeutic benefit in patients with obsessive-compulsive disorder (OCD). To evaluate the effect of chronic FLX treatment on 5-HT1A receptor responsivity, hypothermic, neuroendocrine, and behavioral responses to the selective 5-HT1A receptor ligand ipsapirone (IPS) were examined in patients with primary OCD. A single dose of 0.3 mg/kg of IPS or placebo were given under double-blind, random-assignment conditions to ten patients before and during FLX treatment. The ability of IPS to induce hypothermia and ACTH/cortisol release was significantly attenuated during chronic FLX as compared to the pretreatment IPS challenge. The behavioral effects of IPS, though minimal, were less pronounced during FLX treatment. While FLX was effective in reducing the severity of OC symptoms, no significant correlation between attenuation of 5-HT1A receptor-mediated functional measures and FLX-induced improvement in OC symptoms was detected. These findings are consistent with the development of adaptive hyporesponsivity of the 5-HT1A receptor-effector system complex possibly involving subsensitivity of the 5-HT1A receptor itself and/or decreased functional activity of the postreceptor signal transduction. Modulation of 5-HT1A receptor-effector system function may be critical to the antidepressant/anti-OC efficacy of 5-HT reuptake inhibitors.

Adrenocorticotropic Hormone↗
PubMed1991

Demonstration of calcium in dermal melanocytes of Xenopus laevis and Poecilia reticulata with electron energy-loss spectroscopy and electron spectroscopic imaging.

The subcellular distribution of calcium in dermal melanocytes of Xenopus laevis and Poecilia reticulata has been analysed. Using two cytochemical methods, phosphate precipitation and a combined oxalate-pyroantimonate technique, electron energy-loss spectroscopy and electron spectroscopic imaging have been applied for elemental analysis. Both precipitation techniques revealed a high calcium content in the melanosomes of both species. Calcium was also located in the vicinity of collagen fibrils and in the plasma membrane.

Animals↗
PubMed1991

Structure/activity relationships in basic FGF.

Although the FGFs have been subject to extensive biological studies, only limited progress has been made so far in determining the critical elements of structure-activity relationships in the FGFs. Among the recognized structural elements with potential to affect the biological activity of FGFs are the cysteine residues, and the heparin- and receptor-binding domains. These features have been studied using a variety of experimental approaches, but the available data are inconclusive. For example, ambiguity regarding the presence of a disulfide structure in FGFs was not resolved until the availability of x-ray crystal structure data. Furthermore, the functionally important heparin- and receptor-binding domains have been poorly characterized, with some interpretations being controversial. In this report, we describe a novel fragment of basic FGF (bFGF) with high biological activity [Ser78,96-bFGF(70-153)]. This fragment was generated by pronase treatment of heparin-bound recombinant Glu3,5Ser78,96-bFGF mutant and is active in vitro at an ED50 of about 100 ng/ml. The structure of the fragment and the manner by which it was generated provide additional insight into important aspects of structure-activity relationships in FGFs. Specifically, we conclude that (a) the cysteines in our bFGF mutant do not form a disulfide bond, (b) the high-affinity heparin binding of bFGF critically depends on an intact 3-dimensional structure of the growth factor rather than on specific heparin-binding sequence domains, and (c) the bFGF sequence between residues 70 and 122 is important for high biological activity.

Binding Sites↗
PubMed1991

The role of membrane contact in hemodialysis-induced granulocyte activation.

Besides complement, interleukin-1 and beta 2-microglobulin, activation of granulocyte function has been found out to be the major parameter in the determination of dialyzer biocompatibility. Unfortunately, the term 'granulocyte activation' has been widely used without restriction to distinct functions or definition of the related metabolic pathways. Therefore, the present study aims to elucidate the influence of hemodialysis (HD) pure membrane contact on granulocyte O2- release. The activation of this metabolic pathway which is also known as the so-called oxidative burst has been generally accepted as the initial signal in the granulocyte inflammatory activation cascade. Two membranes which have been previously shown to differ most widely in biocompatibility, cuprophane and polysulfone, have been selected. During HD with cuprophane the stimulatable O2- release was initially decreased, whereas polysulfone HD was effectless on granulocyte oxidative metabolism. The inhibition was due to a prestimulation of the granulocyte by pure interaction of the cell with the surface of the dialyzer membrane which could be proved by evaluating a plasma-free model. Activation of oxidative metabolism was strongly correlated with granulocyte adherence, showing a significantly higher rate of cell adherence in the case of cuprophane. Nevertheless, sheer forces were able to prevent granulocytes becoming adherent directly to the dialyzer membrane, but sheer forces were not able to influence the oxidative burst reaction, suggesting that the membrane-related stimulation of oxidative metabolism occurs immediately after a very short, possibly a single and hasty contact of the cell to the surface of the dialyzer membrane.

Aged↗