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31.
N. Barisic K. G. Claeys M. Sirotkovi-Skerlev A. Löfgren E. Nelis P. De Jonghe V. Timmerman 《Annals of human genetics》2008,72(3):416-441
Charcot‐Marie‐Tooth disease (CMT) is the most common neuromuscular disorder. It represents a group of clinically and genetically heterogeneous inherited neuropathies. Here, we review the results of molecular genetic investigations and the clinical and neurophysiological features of the different CMT subtypes. The products of genes associated with CMT phenotypes are important for the neuronal structure maintenance, axonal transport, nerve signal transduction and functions related to the cellular integrity. Identifying the molecular basis of CMT and studying the relevant genes and their functions is important to understand the pathophysiological mechanisms of these neurodegenerative disorders, and the processes involved in the normal development and function of the peripheral nervous system. The results of molecular genetic investigations have impact on the appropriate diagnosis, genetic counselling and possible new therapeutic options for CMT patients. 相似文献
32.
Mechanical loading stimulates dentin matrix protein 1 (DMP1) expression in osteocytes in vivo. 总被引:3,自引:0,他引:3
Jelica Gluhak-Heinrich Ling Ye Lynda F Bonewald Jian Q Feng Mary MacDougall Stephen E Harris Dubravko Pavlin 《Journal of bone and mineral research》2003,18(5):807-817
Dentin matrix protein 1 (DMP1) was originally postulated to be dentin specific. Further analysis showed that DMP1 is also expressed in mature cartilage and bone. In bone tissue, DMP1 is expressed predominantly in late osteoblasts and osteocytes. DMP1 belongs to the SIBLING (Small Integrin Binding Ligand N-linked Glycoprotein) family of cellular matrix proteins that also includes osteopontin, bone sialoprotein, dentin sialophosphoprotein, and others. In this study, we examined the effect of mechanical loading on expression of DMP1 mRNA and DMP1 protein in alveolar bone in the mouse tooth movement model by in situ hybridization and immunocytochemistry. The expression of DMP1 mRNA was determined quantitatively in mechanically loaded and control sites of dento-alveolar tissue at several time points from 6 h to 7 days after loading. The tooth movement model allows simultaneous evaluation of bone resorption and bone formation sites. Expression of DMP1 mRNA in osteocytes increased 2-fold as early as 6 h after treatment in both the bone formation and bone resorption sites. After 4 days, DMP1 expression in osteocytes increased to a maximum of 3.7-fold in the bone formation sites and 3.5-fold in the resorption sites. Osteoblasts responded in the opposite manner and showed a transient 45% decrease of DMP1 mRNA in bone formation sites and a constant decrease of DMP1 mRNA during the entire course of treatment in the bone resorption sites, with a peak inhibition of 67% at day 2. By immunocytochemistry using a C-terminal region peptide antibody to DMP1, we found that there was a transient decrease in immunoreactivity at 3 days after treatment on both the formation side and the resorption side compared with the matched contralateral control tissue. However by 7 days of loading, there was a dramatic increase in DMP1 protein immunoreactivity on both the formation side and the resorption side. These results represent changes in epitope availability using this antibody or true changes in protein levels. The observations imply that the DMP1 protein is undergoing dynamic changes in either synthesis or other protein/matrix interaction after mechanical loading of alveolar bone. The findings indicate that DMP1 is involved in the responses of osteocytes and osteoblasts to mechanical loading of bone. These results support the hypothesis that osteocytes alter their matrix microenvironment in response to mechanical loading. 相似文献
33.
The increased concern about terrorist use of nerve agents prompted us to search for new more effective oximes against tabun and soman poisoning. We investigated the interactions of five bispyridinium oximes: K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) propane dibromide], K048 [1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide], K033 [1,4-bis(2-hydroxyiminomethylpyridinium) butane dibromide], TMB-4 [1,3-bis(4-hydroxyiminomethylpyridinium) propane dibromide] and HI-6 [(1-(2-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxapropane dichloride)] with human erythrocyte acetylcholinesterase (AChE; E.C. 3.1.1.7) and their effects on tabun- and soman-poisoned mice. All the oximes reversibly inhibited AChE, and the enzyme-oxime dissociation constants were between 17 and 180 microM. Tabun-inhibited AChE was completely reactivated by TMB-4, K027 and K048, with the overall reactivation rate constants of 306, 376 and 673 min(-1)M(-1), respectively. The reactivation of tabun-inhibited AChE by K033 reached 50% after 24h, while HI-6 failed to reactivate any AChE at all. Soman-inhibited AChE was resistant to reactivation by 1mM oximes. All studied oximes protected AChE from phosphorylation with both soman and tabun. In vivo experiments showed that the studied oximes were relatively toxic to mice; K033 was the most toxic (LD50=33.4 mg/kg), while K027 was the least toxic (LD50=672.8 mg/kg). The best antidotal efficacy was obtained with K048, K027 and TMB-4 for tabun poisoning, and HI-6 for soman poisoning. Moreover, all tested oximes showed no cytotoxic effect on several cell lines in concentrations up to 0.8mM. The potency of the oximes K048 and K027 to protect mice from five-fold LD50 of tabun and their low toxicity make these compounds leading in the therapy of tabun poisoning. The combination of HI-6 and atropine is the therapy of choice for soman poisoning. 相似文献
34.
Mikulić D Ilić I Cepulić M Giljević JS Orlić D Zupancić B Fattorini I Seiwerth S 《Journal of pediatric surgery》2006,41(3):524-529
Background/Purpose
Intratumoral angiogenesis quantified by microvessel density (MVD) has been shown to be a strong prognostic indicator in a number of malignant tumors. Its association with prognosis in Ewing sarcoma has not been previously studied. The aim of our study was to investigate the relationship between angiogenesis and clinical outcome in Ewing sarcoma.Methods
Twenty-seven patients with Ewing sarcoma were included in a retrospective immunohistochemical study. Sections from diagnostic biopsies were immunostained using anti-von Willebrand factor antibody and microvessels were counted at 400× magnification on three microscopic fields per patient. Microvessel density was correlated with overall and disease-free survival as a continuous variable using univariate regression analysis and as a dichotomous variable by Kaplan-Meier and log-rank analysis. Correlation between clinicopathologic variables and the degree of angiogenesis was tested using χ2 test.Results
Increasing MVD was not confirmed to be a poor prognostic factor in univariate analysis. Also, statistically significant difference was not found in overall survival or disease-free survival between patients with high (>31.6 vessels per field) and low (≤31.6 vessels per field) microvessel counts. Finally, there was no difference regarding the metastatic rate between patients with high and low microvessel counts.Conclusions
Our results did not confirm increasing angiogenesis quantified by MVD to be predictive of prognosis or pulmonary metastasis in Ewing sarcoma. The diffuse pattern of distribution of microvessels found in Ewing sarcoma may be responsible for the observed lack of prognostic significance of angiogenesis. Future work is required to assess the prognostic importance of MVD in this disease. 相似文献35.
36.
Stojanovic Vesna Vuckovic Nada Barisic Nenad Doronjski Aleksandra 《Stress and health》2011,27(3):e195-e198
Aim of this study was to detect and quantify histological changes in kidneys after exposure to acute and chronic stress. Rats were divided into the groups consisting of 12 animals: control group—freely moving (unstressed); rats subjected to immobilization for 2 h; rats subjected to repeated 2 h immobilization for ten consecutive days; rats subjected to repeated 2 h immobilization for two consecutive days. Eight features of histopathological damage were scored on normal (0) to severe (4) scale. Changes occured in the kidneys during both, acute and chronic stress. The most common type of degeneration is ‘cloudy swelling’ in epithelial cells of proximal and distal tubules and interstitial edema. Chronic stress induces more prominent changes, which inflict more glomeruls than acute stress. Acute and repetitive stress induces mild or moderate histopathologic changes in kidneys. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
37.
Stapled hemorrhoidopexy is becoming a widely accepted surgical treatment for third- and fourth-degree hemorrhoids because
it is associated with much less postoperative pain than open hemorrhoidectomy. After the procedure, a circular line of staples
is left in the anal canal; therefore, there is a risk of penile injury or condom damage during anal intercourse, which increases
the risk of exposure to sexually transmitted diseases. We report the case of a male homosexual patient who engaged in anal
intercourse after recovering from a stapled hemorrhoidopexy, resulting in condom damage. We did not consider this possibility
and neglected to discuss the issue with the patient. With an estimated 2.5% of the general population being exclusive, male
homosexuals, it is necessary to inform such patients to refrain from anal intercourse after hemorrhoidopexy, although there
are no reports stating how long this restraint should last. 相似文献
38.
We describe an opening with smooth walls in front and medial to foramen ovale which leads to an oblique canal directed towards the fossa pterygoidea. The canal was up to 2.3 mm long and opened near the root of the pterygoid process. We called this opening "foramen ovale accessorium", and found it in 48 of 124 anatomical specimens. The foramen was present in newborns and in those aged over 80 years old on one side but rarely on both sides of the sphenoid bone. Only in a single specimen were there two foramina side by side in front of the foramen ovale. In another case, the foramen ovale accessorium was present in the anterior wall of the canalis ovalis and pointed to the fossa pterygoidea. The localization and direction of the foramen ovale accessorium led us to the conclusion that it housed some of the separate rootlets for the chewing muscles, in this case for mm pterygoidei, mm tensor veli palatini and tensor tympani. The existence and contents of the foramen ovale accessorium is important in surgical interventions on the trigeminal nerve and/or ganglion Gasseri. 相似文献
39.
Zenon?Pogoreli?Email author Marijana?Rikalo Miro?Juki? Josip?Kati? Ivo?Juri? Dubravko?Furlan Dra?en?Budimir Mihovil?Bio?i? 《Surgery today》2017,47(1):108-113