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51.
52.
Schoch B Gorissen B Richter S Ozimek A Kaiser O Dimitrova A Regel JP Wieland R Hövel M Gizewski E Timmann D 《Journal of neurophysiology》2004,92(3):1856-1866
More recent findings suggest a possible role of the cerebellum in nonmotor functions. Disability of individuals with cerebellar damage in rapidly shifting attention is one frequently used example to support cerebellar involvement in mental skills. The original proposal was based on findings in five children with chronic surgical lesions of the cerebellum and a young adult with a degenerative disorder. The aim of the present study was to repeat Akshoomoff and Courchesne's initial findings in a larger group of children with focal cerebellar lesions. Ten children with cerebellar lesions and 10 age- and sex-matched controls were tested. Neocerebellar areas were affected in all children with cerebellar damage except one based on detailed analysis of MRI scans. Subjects had to perform a focus and a shift attention task. Two visual and two auditory stimuli were presented in a pseudorandom order. An ellipse and a high-pitched tone were presented less frequently than a circle and a low-pitched tone. Rare stimuli were presented at five different time intervals. In the focus tasks, subjects had to react to the same rare stimulus of one of the two modalities. In the shift task, subjects had to switch between the two rare stimuli. Motor deficits based on reaction times were small in cerebellar children compared with controls. The ability of target detection did not significantly differ in the children with cerebellar lesions compared with the control children in both the focus and the shift attention task. In particular, children with cerebellar damage showed no significant impairment in rapid (<2 s) shifts of attention. The present findings indicate that the cerebellum may be less critical in attention related processes than suggested previously. 相似文献
53.
54.
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
55.
Tosatti S Schwartz Z Campbell C Cochran DL VandeVondele S Hubbell JA Denzer A Simpson J Wieland M Lohmann CH Textor M Boyan BD 《Journal of biomedical materials research. Part A》2004,68(3):458-472
Osteoblasts exhibit a more differentiated morphology on surfaces with rough microtopographies. Surface effects are often mediated through integrins that bind the RGD motif in cell attachment proteins. Here, we tested the hypothesis that modulating access to RGD binding sites can modify the response of osteoblasts to surface microtopography. MG63 immature osteoblast-like cells were cultured on smooth (Ti sputter-coated Si wafers) and rough (grit blasted/acid etched) Ti surfaces that were modified with adsorbed monomolecular layers of a comb-like graft copolymer, poly-(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG), to limit nonspecific protein adsorption. PLL-g-PEG coatings were functionalized with varying amounts of an integrin-receptor-binding RGD peptide GCRGYGRGDSPG (PLL-g-PEG/PEG-RGD) or a nonbinding RDG control sequence GCRGYGRDGSPG (PLL-g-PEG/PEG-RDG). Response to PLL-g-PEG alone was compared with response to surfaces on which 2-18% of the polymer sidechains were functionalized with the RGD peptide or the RDG peptide. To examine RGD dose-response, peptide surface concentration was varied between 0 and 6.4 pmol/cm(2). In addition, cells were cultured on uncoated Ti or Ti coated with PLL-g-PEG or PLL-g-PEG/PEG-RGD at an RGD surface concentration of 0.7 pmol/cm(2), and free RGDS was added to the media to block integrin binding. Analyses were performed 24 h after cultures had achieved confluence on the tissue culture plastic surface. Cell number was reduced on smooth Ti compared to plastic or glass and further decreased on surfaces coated with PLL-g-PEG or PLL-g-PEG/PEG-RDG, but was restored to control levels when PLL-g-PEG/PEG-RGD was present. Alkaline phosphatase specific activity and osteocalcin levels were increased on PLL-g-PEG alone or PLL-g-PEG/PEG-RDG, but PLL-g-PEG/PEG-RGD reduced the parameters to control levels. On rough Ti surfaces, cell number was reduced to a greater extent than on smooth Ti. PLL-g-PEG coatings reduced alkaline phosphatase and increased osteocalcin in a manner that was synergistic with surface roughness. The RDG peptide did not alter the PLL-g-PEG effect but the RGD peptide restored these markers to their control levels. PLL-g-PEG coatings also increased TGF-beta1 and PGE(2) in conditioned media of cells cultured on smooth or rough Ti; there was a 20x increase on rough Ti coated with PLL-g-PEG. PLL-g-PEG effects were inhibited dose dependently by addition of the RGD peptide to the surface. Free RGDS did not decrease the effect elicited by PLL-g-PEG surfaces. These unexpected results suggest that PLL-g-PEG may have osteogenic properties, perhaps correlated with effects that alter cell attachment and spreading, and promote a more differentiated morphology. 相似文献
56.
Angiotensinogen is thought to be an acute-phase protein, since its plasma concentrations increase in response to some inflammatory conditions, e.g. partial hepatectomy, nephrectomy or lipopolysaccharide (LPS) injection. However, this response of angiotensinogen has never been related to that of established acute-phase proteins. We have, therefore, examined plasma concentrations and hepatic secretion of angiotensinogen in two widely used inflammation models, i.e. turpentine or LPS injection in the rat, as well as in nephrectomized and sham-nephrectomized rats, in comparison to the response of two established acute-phase proteins, 1-acid glycoprotein (AGP) and 1-macroglobulin (AMG). Plasma concentrations and secretion rates of AGP and AMG increased significantly in all the conditions examined. The magnitude of the response decreased in the order turpentine > nephrectomy = LPS > sham nephrectomy. Angiotensinogen secretion was stimulated in LPS-injected (2.5-fold) and nephrectomized rats (2.6-fold), whereas no changes were seen in sham-nephrectomized rats. Surprisingly, a significant decrease both in secretion rates and plasma concentrations of angiotensinogen occurred in turpentine-injected rats.Intraperitoneal injection of interleukin 6, a major inductor of hepatic acute-phase proteins, increased plasma concentrations and hepatic secretion rates of AGP, AMG and angiotensinogen. Changes in liver angiotensinogen mRNA correlated well with angiotensinogen secretion rates in all groups, indicating that alterations in angiotensinogen synthesis are responsible for the observed changes in secretion rates and plasma concentrations. The response of angiotensinogen to turpentine is difficult to reconcile with the conventional definition of an acute-phase protein. 相似文献
57.
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
58.
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
59.
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
60.
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