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31.
Iduronate-2-sulfatase gene mutations in 16 patients with mucopolysaccharidosis type II (Hunter syndrome) 总被引:4,自引:0,他引:4
Bunge Susanna; Steglich Cordula; Zuther Cornelia; Beck Michael; Morris C. Phillip; Schwinger Eberhard; Schinzel Albert; Hopwood John J.; Gal Andreas 《Human molecular genetics》1993,2(11):1871-1875
Mutations of the iduronate-2-sulfatase gene were identifiedin 16 patients with mucopolysaccharidosis type II (Hunter syndrome).Together with another 10 cases reported by us earlier it emergesthat about 20% of the patients have deletions of the whole geneor other major structural alterations. One, two or three basepair deletions are found in about 23% of the cases while theremaining about 57% carry point mutations predicting amlno acidreplacement, premature termination of translation, or aberrantsplicing. Molecular analysis of mRNA in splice site mutantsshowed that these latter defects frequently resulted in useof cryptic splice sites in exons or introns. 62% of the smalldeletions and point mutations have occurred in 3 of the 9 iduronate-2-sulfatasegene exons. Knowledge of the primary genetic defect allows fastand reliable carrier detection and prenatal diagnosis as wellas insight into the relationship between genotype and phenotype. 相似文献
32.
Transport of organic cations (OC) is important for the recycling of endogenous OC and also a necessary step for detoxification of exogenous OC in the body. Even though the identification and characterisation of numerous OC transporters in recent years has allowed the elucidation of molecular mechanisms underlying OC transport, elucidation of the regulation of this transport is just beginning. This review summarises the general properties of OC transport and then analyses the literature on the regulation of these processes. Studies on short- and long-term regulation of OC transport are considered separately. Important aspects of short-term regulation have been clarified and the regulatory pathways of several OC transporters have been characterised. Short-term regulation appears to be transporter subtype-, tissue- and species-dependent and to involve transporter phosphorylation. Transporter phosphorylation may alter the affinity for substrates or/and expression on the plasma membrane. Even though several studies have shown long-term regulation of OC transport, the pathophysiological meaning of these changes are not well understood. In this case, regulation seems to be subtype-, tissue- and gender-specific. Further research is necessary to clarify this important issue of regulation of OC transport. 相似文献
33.
The Bloom's Syndrome Registry was published in this journal in 1977. Now, in the first in a series of progress reports, recent accessions to the Registry are recorded, new instances of neoplasia are listed, and recent clinical observations and experimental results of general interest are cited. 相似文献
34.
T. Deufel I. Paetzke D. Pongratz G. Hübner O. H. Wieland 《Journal of molecular medicine (Berlin, Germany)》1984,62(14):651-658
Summary In the diagnosis of metabolic myopathies the use of biochemical methods, in addition to morphological examination of muscle biopsies, is often necessary in order to identify a specific metabolic defect. In order to narrow down the spectrum of biochemical methods, extensive clinical investigation and morphological examination, including histology, enzyme histochemistry and electromicroscopy if necessary have to be done beforehand. Patients are classified in the following groups: 1) progressive muscular weakness and/or muscle wasting with storage of a) glycogen, b) lipid or c) mitochondrial alterations; 2) recurrent rhabdomyolysis induced by fasting or exercise a) with glycogen storage or b) without any specific morphological alterations. The spectrum of metabolic defects comprises disorders of glycogen and glucose metabolism (deficiency of acid maltase, debranching and branching enzyme, phosphorylase, phosphofructokinase and other glycolytic enzymes), lipid metabolism (carnitine deficiency, carnitine palmitoyl transferase deficiency), mitochondria (respiratory chain disorders, pyruvate dehydrogenase deficiency) and others such as adenylate deaminase deficiency. In some of these e.g. infantile acid maltase deficiency and mitochondriopathies, it is clinically more important when organs other than muscle are affected; however, muscle biopsy is a useful substrate for diagnosis of these metabolic disorders.
Mit Unterstützung durch die DFG und die Friedrich Baur Stiftung, München 相似文献
35.
Implanted biomaterials are coated immediately with host plasma constituents, including extracellular matrix (ECM); this reaction may be undesirable in some cases. Poly(L-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG) has been shown to spontaneously adsorb from aqueous solution onto metal oxide surfaces, effectively reducing the degree of non-specific adsorption of blood and ECM proteins, and decreasing the adhesion of fibroblastic and osteoblastic cells to the coated surfaces. Cell adhesion through specific peptide-integrin receptors could be restored on surfaces coated with PLL-g-PEG functionalized with peptides of the RGD (Arg-Asp-Gly) type. To date, no study has examined the effect of surface modifications by PLL-g-PEG-based polymers on bacterial adhesion. The ability of Staphylococcus aureus to adhere to the ECM and plasma proteins deposited on biomaterials is a significant factor in the pathogenesis of medical-device-related infections. This study describes methods for visualizing and quantifying the adhesion of S. aureus to smooth and rough (chemically etched) titanium surfaces without and with monomolecular coatings of PLL-g-PEG, PLL-g-PEG/PEG-RGD and PLL-g-PEG/PEG-RDG. The different surfaces were exposed to S. aureus cultures for 1-24h and bacteria surface density was evaluated using scanning electron microscopy and fluorescence microscopy. Coating titanium surfaces with any of the three types of copolymers significantly decreased the adhesion of S. aureus to the surfaces by 89-93% for PLL-g-PEG, and 69% for PLL-g-PEG/PEG-RGD. Therefore, surfaces coated with PLL-g-PEG/PEG-RGD have the ability to attach cells such as fibroblasts and osteoblasts while showing reduced S. aureus adhesion, resulting in a selective biointeraction pattern that may be useful for applications in the area of osteosynthesis, orthopaedic and dental implantology. 相似文献
36.
Nikol S Maier A Krausz E Höfling B Huehns TY 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》1998,9(5):375-388
No systemic pharmacological treatment has been convincingly shown to reduce the incidence of restenosis after angioplasty in patients. The lack of success of many pharmaceutical agents in reducing restenosis rates post-angioplasty and following stent implantation, as documented in dozens of clinical trials, has encouraged the development of new biotechnological approaches to the treatment of restenosis. Gene therapy and other agents, including antibodies, fusion toxins and ribozymes, have the potential to prevent some of the sequelae after arterial injury, particularly cell proliferation. Mechanical methods of preventing restenosis, for example sophisticated local drug delivery strategies and biodegradable stents using new materials, in combination with novel therapeutic agents or radiation, may also be of use. 相似文献
37.
Ilkka Pörsti Markus Hecker Eberhard Bassenge Rudi Busses 《Naunyn-Schmiedeberg's archives of pharmacology》1993,348(6):650-658
Summary We studied the functional role of angiotensin II (AII) receptor subtypes and vasodilatory endothelial autacoid release in response to AII in isolated perfused rabbit hearts. AII infusion induced biphasic changes in coronary perfusion pressure (CPP): an initial increase was followed by a decrease until a plateau was reached. At higher concentrations of AII (10 nmol/l) this plateau phase was lower than the initial CPP level. AII infusion elicited inverse changes in peak left ventricular pressure (LVP): coronary constriction was associated with a transient decline, and during the plateau phase LVP was clearly increased. AII also moderately augmented prostacyclin (PGI2) release from the coronary vascular bed. The AII-induced changes in CPP, LVP, and PGI2 release were effectively inhibited by the AT1 receptor subtype antagonist ICI D8731 (30 nmol/l), but not by the AT2 receptor antagonist CGP 42112 (30 nmol/l). The adenosine A1 receptor antagonist 8-phenyltheophylline (0.1 mol/l) attenuated the decline in CPP following the constriction phase without affecting the changes in LVP during AII infusion. The cyclooxygenase inhibitor diclofenac (1 mmol/l) had no effect on the AII-induced changes in CPP, whereas the nitric oxide-synthase inhibitor NG-nitro-L-arginine (30 mol/l) markedly potentiated the vasoconstriction but was without effect on the plateau phase of the response. In contrast to AII, the thromboxane analogue U46619 elicited sustained increases in CPP which were associated with slight decreases in LVP.In conclusion, AII induced a biphasic pressor response in the rabbit coronary vascular bed consisting of a transient vasoconstriction followed by a dilatation especially at higher concentrations of AII, an effect which was independent of the endothelial autacoids nitric oxide and PGI2. The AII-induced dilatation probably reflected rapid desensitization of the coronary arterial smooth muscle to the constrictor effect, and the concomitant accumulation of vasodilatory metabolites such as adenosine, generated during the positive inotropic action of AII. All the effects of AII in the rabbit heart appeared to be mediated via the AT, receptor subtype localized on coronary endothelial and smooth muscle cells, as well as on cardiomyocytes.On leave from the Department of Biomedical Sciences, University of Tampere, P.O. Box 607, FIN-33101 Tampere, FinlandCorrespondence to: I. Pörsti 相似文献
38.
Eberhard Schlicker Walter Schunack Manfred Göthert 《Naunyn-Schmiedeberg's archives of pharmacology》1990,342(5):497-501
Summary Discs of pig retina were preincubated with 3H-noradrenaline, 3H-dopamine or 3H-serotonin and then superfused. Electrical field stimulation increased the outflow of tritium from discs preincubated with 3H-noradrenaline or 3H-dopamine, but no from discs preincubated with 3H-serotonin. The tritium content at the end of superfusion was similar in discs preincubated with 3H-noradrenaline or 3H-dopamine but about tenfold lower in discs preincubated with 3H-serotonin. The tritium content in discs preincubated with 3H-noradrenaline was markedly reduced when desipramine was present during preincubation but was not affected by selective inhibitors of dopamine and serotonin uptake. The tritium content in discs preincubated with 3Hdopamine and 3H-serotonin, in contrast, was reduced or tended to be reduced by a selective dopamine and serotonin uptake inhibitor, respectively.The electrically evoked overflow of tritium from discs preincubated with 3H-noradrenaline was abolished by tetrodotoxin or omission of Ca2+. In discs superfused with desipramine, the electrically evoked overflow was enhanced by phentolamine but not affected by histamine. When both desipramine and phentolamine were present in the superfusion medium, histamine inhibited the evoked overflow (pIC15 6.85). This effect was mimicked by the histamine H3 receptor agonist R-(–)--methylhistamine as well as by its S-(+)-enantiomer (pIC15 7.85 and 5.30, respectively) but not by the H1 receptor agonist 2-(2-thiazolyl)ethylamine and the H2 receptor agonist dimaprit (each 10 mol/l). The inhibitory effect of histamine was abolished by the H3 receptor antagonist thioperamide 0.32 mol/l and attenuated by impromidine 3.2 mol/l but not affected by the H1 receptor antagonist dimetindene 3.2 mol/l and the H2 receptor antagonist ranitidine 10 mol/l.The results suggest that, in the pig retina, noradrenaline is taken up into, and released from, noradrenergic neurones (most likely vascular postganglionic sympathetic nerve fibres, less probably tissue-specific noradrenergic neurones of the retina) and that noradrenaline release is subject to modulation via H3 receptors and probably also a-adrenoceptors.Send offprint requests to E. Schlicker at the above address 相似文献
39.
Involvement of nitric oxide synthase in the physiology and pathophysiology of facial nerve function and dysfunction 总被引:1,自引:0,他引:1
O. Michel Alexander Hess Martin Krolzig Eberhard Stennert Klaus Addick Wilhelm Bloch 《European archives of oto-rhino-laryngology》2000,257(4):188-192
To date few reports have discussed the presence and function of nitric oxide (NO) in structures of the facial nerve. We performed
nicotinamide adenine dinucleotide phosphate (NADPH-d)-diaphorase-histochemistry and immunohistochemistry on the intratemporal
portion of the facial nerve, including the geniculate ganglion, of guinea pigs using specific antibodies to the three known
isoforms of NO synthase and soluble guanylyl-cyclase (sGC). Normal facial nerves were compared to those treated intratympanically
with bacterial lipopolysaccharides (LPS) and tumor necrosis factor-α (TNF-α). Both constitutive NOS isoforms and sGC could
be detected in the bipolar ganglion cells of normal animals, while the inducible isoform (iNOS or NOS II) was not found. Endothelial
NOS (NOS III) and sGC were present in blood vessels and were predominantly found in the perineurial sheath and less in the
endoneurium. sGC could be detected in all fibers in a cross section of the facial nerve. LPS and TNF treatment led to the
detection of iNOS in the perikaryia of the geniculate ganglion and the perineural sheath. These findings imply that NO may
be involved in neurotransmission at least in the visceroafferent system. NO regulates vascular tone of nutrient blood vessels
in the perineural sheath and endoneurium. The presence of sGC indicates that NO acts via its second messenger cGMP. NOS II
expression may be a contributing factor to facial nerve palsy via two different mechanisms: NOS II-generated NO may lead to
an overstimulation of the visceroefferent nerve fibers and motor fibers of the facial nerve. Dysregulation in facial nerve
blood vessels could lead to edema and elevated pressure on the nerve within its osseous canal.
Received: 13 April 1999 / Accepted: 12 August 1999 相似文献
40.
A. Wolkin E. Duncan M. Sanfilipo S. Wieland T. B. Cooper J. Rotrosen 《Journal of neural transmission (Vienna, Austria : 1996)》1994,95(1):49-61
Summary The purpose of this study was to evaluate the hypothesis that neuroleptic non-response in the face of adequate DA post-synaptic receptor blockade reflects failure of regulatory mechanisms to decrease DA pre-synaptic activity. Eight chronic schizophrenics, meeting rigorous criteria for neuroleptic non-response, were treated for four weeks with alpha-methylparatyrosine as an adjunct to their previously stable neuroleptic dose. Treatment with AMPT produced a prompt decrease in plasma HVA that was, on average, 72% lower at the end of the study. While there was also strong clinical evidence of reduction in central dopaminergic activity (both a significant reduction in dyskinetic movements and increase in extrapyramidal symptoms), there was virtually no change in severity of psychotic symptoms. Thus, in this group of non-responders, psychotic symptoms persisted despite both extensive dopamine post-synaptic receptor blockade and marked reduction of presynaptic activity. These symptoms may not be directly DA dependent. 相似文献