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Biomedical subjects

G Fischer

Publications and source records attributed to G Fischer.

At least 343 records · Page 19Linked to original sources
PubMed1992

Neurofibromatosis type 2 appears to be a genetically homogeneous disease.

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome characterized by the development of vestibular schwannomas and other tumors of the nervous system, including cranial and spinal meningiomas, schwannomas, and ependymomas. The presence of bilateral vestibular schwannomas is sufficient for the diagnosis. Skin manifestations are less common than in neurofibromatosis type 1 (NF1; von Recklinghausen disease). The apparent clinical distinction between NF1 and NF2 has been confirmed at the level of the gene locus by linkage studies; the gene for NF1 maps to chromosome 17, whereas the gene for NF2 has been assigned (in a single family) to chromosome 22. To increase the precision of the genetic mapping of NF2 and to determine whether additional susceptibility loci exist, we have performed linkage analysis on 12 families with NF2 by using four polymorphic markers from chromosome 22 and a marker at the NF1 locus on chromosome 17. Our results confirm the assignment of the gene for NF2 to chromosome 22 and do not support the hypothesis of genetic heterogeneity. We believe that chromosome 22 markers can now be used for presymptomatic diagnosis in selected families. The NF2 gene is tightly linked to the D22S32 locus (maximum lod score 4.12; recombination fraction 0). A CA-repeat polymorphism at the CRYB2 locus was the most informative marker in our families (lod score 5.99), but because the observed recombination fraction between NF2 and CRYB2 was 10 cM, predictions using this marker will need to be interpreted with caution.

Chromosomes, Human, Pair 17↗
PubMed1991

Peptidyl-prolyl cis-trans isomerase activity as studied by dynamic proton NMR spectroscopy.

Recently the identity of the peptidyl-prolyl cis-trans isomerase (PPIase), which accelerates the cis/trans isomerization of prolyl peptide bonds and cyclophilin, the binding protein for the immunosuppressive drug Cyclosporin A (CsA), was discovered. The PPIase catalysis toward the substrate Suc-Ala-Phe-Pro-Phe-pNA has been studied by 1H NMR spectroscopy. Using the bandshape analysis technique the rate of interconversion between the cis and trans isomers of the substrate could be measured in the presence of PPIase and under equilibrium conditions. The acceleration is inhibited by equimolar amounts of CsA. The results provide evidence that the PPIase catalysis is more complex than a simple exchange between two states.

Amino Acid Isomerases↗
PubMed1991

Conformational analysis of the tetrapeptide Pro-D-Phe-Pro-Gly in aqueous solution.

Conformational investigations of the tetrapeptide Pro-D-Phe-Pro-Gly in water solution were carried out by 1H and 13C NMR spectroscopy. The internal proline residue allows for the possibility of cis/trans isomerization about the D-Phe-Pro peptide bond resulting in two conformational isomers. The major isomer was identified as the trans isomer. The pH-dependence of the cis/trans equilibrium supports an additional stabilisation of the trans isomer by an intramolecular ionic interaction between the amino- and carboxy-terminus in the zwitterionic state. Based on 13C spin-lattice relaxation times (T1), different pyrrolidine ring conformations of Pro1 and Pro3 could be determined. By combination of several NMR data (vicinal coupling constants 3JN alpha, temperature dependence of the NH chemical shifts, differences in the chemical shifts between the beta and gamma carbons of the proline residues) and energy minimization calculations, a type II' beta-turn should contribute considerably to the overall structure of the trans isomer.

Endorphins↗
PubMed1991

Catalysis of protein folding by cyclophilins from different species.

Cyclophilins are a class of ubiquitous proteins with yet unknown function. They were originally discovered as the major binding proteins for the immunosuppressant cyclosporin A. The only known catalytic function of these proteins in vitro is the cis/trans isomerization of Xaa-Pro bonds in oligopeptides. This became clear after the discovery that bovine cyclophilin is identical with porcine prolyl isomerase. This enzyme accelerates slow, proline-limited steps in the refolding of several proteins. Here we demonstrate that the cyclophilins from man, pig, Neurospora crassa, Saccharomyces cerevisiae, and Escherichia coli are all active as prolyl isomerases and as catalysts of protein folding. This evolutionary conservation suggests that catalysis of prolyl peptide bond isomerization may be an important function of the cyclophilins. It could be related with de novo protein folding or be involved in regulatory processes. Catalysis of folding is very efficient in the presence of the high cellular concentrations of prolyl isomerase.

Amino Acid Isomerases↗
PubMed1991

Arachidonic acid release by basophilic leukemia cells and macrophages stimulated by Ca2+ ionophores, antigen and diacylglycerol: essential role for protein kinase C and prevention by glucocorticosteroids.

The role of protein kinase C in phospholipase A2 (PLA2) activation in rat basophilic leukemia cells (RBL-2H3) and macrophages was investigated. 12-O-Tetradecanoyl phorbol 13-acetate (TPA) doubled ionomycin-induced PLA2 activity, assessed by [3H]arachidonate release. Protein kinase C inhibitors, staurosporine and K252a (100 nM) or H-7 (15 micrograms/ml) inhibited ionomycin-stimulation of PLA2 activity by 62, 75 and 80%, respectively. Down-regulation of protein kinase C by prolonged treatment with TPA inhibited Ca2(+)-ionophore A23187 or antigen-stimulation of [3H]arachidonate release by 80%. We examined whether the inhibitory effect of dexamethasone (DEX) on PLA2 activity is related to modulation of protein kinase C activity. The 50% inhibition by DEX of ionomycin elevation of [3H]arachidonate release was almost overcome by addition of TPA. The Ca2+ ionophore and antigen-induced increase in [3H]TPA binding to intact RBL cells was not impaired by DEX. However, DEX markedly reduced phosphorylation of several proteins. 1-Oleoyl-2-acetyl-glycerol (OAG) had a sustained stimulatory effect on PLA2 activity in isolated plasma membranes derived from treated bone-marrow intact mouse macrophages, while both DEX and staurosporine reduced elevated PLA2 activity by 68 and 84%, respectively. The results support an essential role for protein kinase C in regulation of PLA2 activity.

Alkaloids↗
PubMed1991

Aminopropylsilane treatment for the surface of porous glasses suitable for enzyme immobilisation.

During silylation of porous glass with 3-aminopropyltriethoxysilane, the properties of the carrier affected the concentration of bound amino groups, the formation of aminopolysiloxane mono- or multilayer on the surface, and the hydrolytic stability of the layer formed. The influence of the carrier depended on the specific surface area and the size of pores. In contrast to silylation performed in organic solvents, in aqueous solutions a monolayer of aminopolysiloxane of high hydrolytic stability was formed on the surface of porous glass. Tetraethoxysilane modification of porous glass prior to silylation with aminosilane yields carriers of increased hydrolytic stability. Glucoamylase immobilised on carriers, that were modified in aqueous solutions, exhibit higher enzymatic activity.

Biotechnology↗
PubMed1991

Lectin binding pattern in the embryonal and early fetal human vertebral column.

Paraffin sections from vertebral columns of ten human embryos and fetuses ranging from stage 16 to the 12th week were stained with the FITC-coupled lectins PNA, RCA I, Con A and WGA in order to investigate changes in carbohydrate-binding sites during vertebral development. PNA revealed a specific binding site in the vertebral body blastema in the precartilaginous stage of development. Beginning with the 25-mm CRL embryo, PNA-binding sites occurred in the developing fibrous annulus and the inner zone of the intervertebral discs. The first binding sites for RCA I were seen in the extracellular matrix of vertebral bodies during the cartilaginous stage of vertebral development. During early ossification of the vertebrae, staining for RCA I-binding sites in the cytoplasm of the chondrocytes and the area around the future cartilaginous end-plates was observed. Con A bound to the chondrocyte cytoplasm, and also very strongly to notochordal cells in all developmental stages examined. WGA-binding sites appeared simultaneously with cartilage formation. Connective tissue components, e.g. ligaments, were diffusely stained by WGA. Also this lectin showed an affinity for vertebral body chondrocytes. We discuss the biochemical aspects of these lectin-binding sites, and their possible roles in the differentiation process of the human vertebral column. The results of this first lectin histochemical study on human vertebral development are compared with related results in other species.

Binding Sites↗
PubMed1991

Reduction of transmural oesophageal variceal pressure by metoclopramide.

In nineteen patients with portal hypertension and oesophageal varices, transmural variceal blood pressure was determined endoscopically by direct puncture of the varices before and after intravenous administration of 20 mg metoclopramide or placebo. No change in pressure was observed after placebo (mean difference -1.3 +/- 24.5%, N.S.), however, metoclopramide reduced the pressure by 17.6 +/- 18.6% (p = 0.02). Our results suggest that metoclopramide may be beneficial for the prevention or treatment of variceal haemorrhage.

Aged↗
PubMed1991

Variceal injection sclerotherapy.

With the development and widespread use of flexible endoscopes, injection sclerotherapy of oesophageal varices has advanced beyond the early stages. Although slightly different techniques and different sclerosants are used, the results are not strikingly different. The cumulative rate of adverse effects is in the range of 20 to 40%, with a procedure-related mortality of around 1 to 2%. Sclerotherapy is the best available treatment for haemostasis of acute oesophageal variceal bleeding. However, as a long-term therapy it is less effective in the prevention of recurrent gastrointestinal bleeding events, since obliteration of all varices often takes several months. Furthermore, extra-oesophageal bleeding is not amenable to sclerotherapy. Thus, if repeated injections fail to prevent recurrent bleeding, other options such as shunt surgery, transection, chronic medical portal decompression with beta-blockers or even liver transplantation should be considered according to the needs of the individual patient. Prophylaxis of first variceal haemorrhage was beneficial in selected patients with a high bleeding risk. It cannot, however, be generally recommended at present.

Duodenoscopy↗
PubMed1991

Alpha 1-adrenoceptor blockade and/or 5-HT1A agonism during treadmill exercise in dogs.

1. The hypotensive effects of alpha 1-adrenergic blockade and/or stimulation of central nervous 5-HT1A receptors were studied using drugs with different affinity for central nervous 5-HT1A and peripheral alpha 1-adrenoceptors. Urapidil, 5-methylurapidil, flesinoxan and 8-OH-DPAT were compared under states of different activation of the autonomic nervous system, i.e. at rest and during graded treadmill exercise. 2. The rank order of hypotensive potency as derived from the most extensive decrease in resting diastolic arterial blood pressure was urapidil greater than 5-methylurapidil greater than flesinoxan much greater than 8-OH-DPAT. 3. The reflex increase in heart rate due to the decrease in arterial blood pressure at rest was suppressed after 0.1 mumol kg-1 flesinoxan. 4. The reflex increase in heart rate due to the decrease in arterial blood pressure at rest was less accentuated after high doses of urapidil and 5-methylurapidil. 5. During exercise both 5HT1A receptor agonists, flesinoxan and 8-OH-DPAT, decreased sympathetic tone. 6. The combined effects of alpha 1-adrenoceptor blockade and 5-HT1A receptor stimulation (urapidil and 5-methylurapidil) result in distinct decreases in blood pressure and slight suppression of reflex tachycardia at rest after high doses. Stimulation of 5-HT1A receptors alone (flesinoxan) suppresses reflex tachycardia by modulation of baroreceptor reflex and at high dose also diminishes exercise-induced increase in sympathetic tone.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Liposculpture. 3. Surgical technique in liposculpture.

The guided liposuction cannula offers the surgeon the advantage of making tunnels that are parallel to the skin's surface. The tunnels are made approximately 1 cm from the skin surface, leaving a uniform fatty layer that covers the deeper tunneling performed with a swan-necked cannula. Anesthesia is administered using the tumescent mixture. Vertical tunnels, parallel to the forces of gravity (when the patient is standing), are made to avoid the draping effect seen in tunnels made in a bicycle-wheel pattern between 50 to 130 degrees and 230 to 210 degrees. The vertical tunnels are important for an acceptable cosmetic result.

Humans↗
PubMed1991

Dislocation and fracture-dislocation of the hip.

Of 54 patients with posterior dislocations of the hip of type I and type II (Stewart and Milford 1954), 47 were followed for a mean period of 6.7 years (2 to 11). Of these, 23 had dislocation with minimal lesions of the acetabulum (type I) and 24 had an avulsed dorsocranial fragment (type II). All were reduced by closed methods within six hours. The subsequent treatment of type I dislocations was conservative. At the beginning of the period type II injuries were treated conservatively, but surgery was increasingly chosen for later cases. Type I dislocations had significantly better results (p < 0.05) than type II fracture-dislocations, regardless of the method of treatment. There were no essential differences between the results of surgical and conservative treatment in type II dislocations.

Adolescent↗
PubMed1991

Conservative treatment of upper gastrointestinal bleeding in portal hypertension.

The main aim of conservative treatment of upper gastrointestinal bleeding in portal hypertension is aim to treat and prevent esophageal variceal hemorrhage. Controlled trials show that the hemostasis rate following vaso-active therapy (vasopressin and analogues, somatostatin) is only slightly superior to the spontaneous hemostasis rate. Complications caused by vasopressin treatment can be avoided by concomitant application of nitroglycerin or by alternative treatment with somatostatin. Balloon tamponade is slightly superior to vasopressin for arresting variceal hemorrhage. Injection sclerotherapy influences acute bleeding most positively. Analysis of controlled trials favors sclerotherapy for prophylaxis of rebleeding, but beta-adrenoceptor blockers appear to be almost equally good.

Adrenergic beta-Antagonists↗