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21.
Tao Yang Roberto Mendoza-Londono Huifang Lu Jianning Tao Kaiyi Li Bettina Keller Ming Ming Jiang Rina Shah Yuqing Chen Terry K. Bertin Feyza Engin Branka Dabovic Daniel B. Rifkin John Hicks Milan Jamrich Arthur L. Beaudet Brendan Lee 《The Journal of clinical investigation》2010,120(7):2474-2485
The majority of human skeletal dysplasias are caused by dysregulation of growth plate homeostasis. As TGF-β signaling is a critical determinant of growth plate homeostasis, skeletal dysplasias are often associated with dysregulation of this pathway. The context-dependent action of TFG-β signaling is tightly controlled by numerous mechanisms at the extracellular level and downstream of ligand-receptor interactions. However, TGF-β is synthesized as an inactive precursor that is cleaved to become mature in the Golgi apparatus, and the regulation of this posttranslational intracellular processing and trafficking is much less defined. Here, we report that a cysteine-rich protein, E-selectin ligand–1 (ESL-1), acts as a negative regulator of TGF-β production by binding TGF-β precursors in the Golgi apparatus in a cell-autonomous fashion, inhibiting their maturation. Furthermore, ESL-1 inhibited the processing of proTGF-β by a furin-like protease, leading to reduced secretion of mature TGF-β by primary mouse chondrocytes and HEK293 cells. In vivo loss of Esl1 in mice led to increased TGF-β/SMAD signaling in the growth plate that was associated with reduced chondrocyte proliferation and delayed terminal differentiation. Gain-of-function and rescue studies of the Xenopus ESL-1 ortholog in the context of early embryogenesis showed that this regulation of TGF-β/Nodal signaling was evolutionarily conserved. This study identifies what we believe to be a novel intracellular mechanism for regulating TGF-β during skeletal development and homeostasis. 相似文献
22.
Tiffany T.Y. Huang Li-Hong He M. Ali Darendeliler Michael V. Swain 《Acta biomaterialia》2010,6(12):4553-4559
Our objectives were to correlate the mineral density (MD) and elastic modulus (E) of natural white spot lesions (WSLs) and compare them with analytical and numerical models. Five natural WSLs from four extracted sound premolar teeth were scanned at a voxel size of 7.6 μm using a desktop X-ray microtomography (XRMT) system. Five hydroxyapatite phantoms with densities ranging from 1.52 to 3.14 g cm?3 were used as calibration standards for each scan. MD throughout the WSLs was quantified using an MD calibration equation derived from hydroxyapatite phantoms. Subsequently, teeth were cross-sectioned and the E modulus was measured systematically across the WSLs at intervals of 25 and 50 μm using nanoindentation. The MD and E modulus of WSLs correlated well. The relationship may be expressed as E = E0 exp?bP (R2 = 0.952) with E0 the elastic modulus of the fully dense material, P the porosity and b a constant. The results for sound enamel were compared with Spears model. The limitation of Spears model to the WSLs is discussed and an alternative model developed by Rice for porous materials is proposed. Clinical implications of this work for quantifying de-/remineralization of teeth are pointed out. We conclude that XRMT can be utilized to extrapolate the E modulus of WSLs. This provides a basis for non-destructive, longitudinal analysis of WSLs in de-/remineralization studies of enamel. 相似文献
23.
F Darendeliler E A Livesey P C Hindmarsh C G Brook 《Acta paediatrica Scandinavica》1990,79(10):950-956
We have studied the growth of 144 children after treatment of brain tumours distant from the hypothalamo-pituitary axis. All had cranial irradiation and 87 spinal irradiation. In 56 patients observed without intervention for 3 years, height SDS in the cranial (CR) group (n = 20) declined from 0.02 to -0.44 and in the craniospinal (CS) group (n = 36) from -0.28 to -1.11. Failure of spinal growth had a marked effect in the CS group. The onset of puberty was slightly but not significantly advanced; median ages at onset of puberty were 10.3 years in girls and 12.1 years in boys. Of the total group 86.4% had clinical and biochemical evidence of growth hormone insufficiency. Fifty-two children, 33 (28 CS; 5 CR) of whom were prepubertal, received biosynthetic human growth hormone, in a dose of 15 mU/m2/week by daily injection for a period of one year. Height velocity SDS increased significantly in both groups from -2.74 to +1.90 (CS) and from -1.0 to +4.26 (CR). Spinal response to GH treatment was restricted in the craniospinal group. 相似文献
24.
We have previously reported that peroxynitrite (ONOO(-)) caused relaxations on isolated rat anococcygeus muscle and in the present study the possible mechanisms of the relaxant effect were investigated. ONOO(-) (0.03- 1.0 mmol/l)-induced relaxations were reduced significantly by the presence of an ATP-sensitive potassium channel (K(+)(ATP) channel) blocker, glibenclamide (0.3 micromol/l), or 1H-(1,2,4)oxadiazolo(4,3-alpha)quinoxalin-1-one (ODQ) (30.0 micromol/l), a guanylyl cyclase inhibitor. However, 3-aminobenzamide (3.0 mmol/l), an inhibitor of poly(ADP- ribose)synthase, did not influence the relaxant effect of ONOO(-) (1.0 mmol/l). Results of the present study implicate that activation of K(+)(ATP) channels and/or cGMP/K(+)(ATP) channel interaction might play a role in the relaxant responses to ONOO(-) in isolated rat anococcygeus muscle. 相似文献
25.
Arslanoğlu I Saka N Bundak R Günöz H Darendeliler F 《Journal of pediatric endocrinology & metabolism : JPEM》2000,13(3):313-318
Insulin injection is a problem in pediatric and adolescent age, and premixed insulin therapy given in pen-injectors (Novopen II) is expected to increase compliance. Compliance with treatment and safety of this kind of insulin substitution was investigated in 20 IDDM patients (8.2-19.6 years old). The study was of randomized cross-over design and its duration was 6 (2x3) months. Metabolic parameters were compared between premixed insulin therapy via pen-injector and patient-mixed insulin therapy via conventional syringe, and no differences were observed except for the postponing of night hypoglycemic attacks to 07.00 a.m. during premixed insulin therapy. No technical or medical problems occurred. Patients were more satisfied with the new therapy regimen as determined by questionnaire. We concluded that this kind of insulin substitution is safe in pediatric and adolescent IDDM patients. 相似文献
26.
Poyrazoğlu S Günöz H Darendeliler F Saka N Bundak R Baş F 《Journal of pediatric endocrinology & metabolism : JPEM》2005,18(2):171-179
This retrospective study evaluated clinical characteristics of patients with constitutional delay of growth and puberty (CDGP) at presentation, during puberty and at final height. The records of 151 children (105 boys, 46 girls) with CDGP were reviewed and the results were evaluated with respect to findings in healthy Turkish schoolchildren. CDGP was twice as frequent in boys as in girls. Height and weight deficit and short sitting height of the children were evident at presentation and continued up to final height. Mean age of onset of puberty was retarded by 2.5 years in girls and by 3 years in boys. The time between onset of puberty and pubertal growth spurt was shorter in both girls and boys than in the controls. Peak growth velocity was compromised in both girls and boys. Forty-one patients (30 boys, 11 girls) reached final height (FH). Mean FH was shorter than both target height and predicted adult height. The Bayley-Pinneau method was found to be a better predictor of FH than either the Tanner-Whitehouse method or target height. FH also showed correlation with the father's height. There was no effect of testosterone treatment on final height. Height deficit at onset of puberty, shorter duration between onset of puberty and pubertal growth spurt, compromised peak growth velocity and short upper segment due to delayed puberty, are findings which may explain the decreased final height of children with CDGP. 相似文献
27.
28.
Paradoxical enlargement of intracranial tuberculomas or development of new ones during adequate antituberculous chemotherapy is an uncommon event. Treatment of such cases is controversial. Steroid therapy is usually advocated without change in the antituberculous drug program. However, in some patients whose lesions fail medical treatment, or who have superficially located large lesions, surgical therapy may be required. A 15-year-old girl with pulmonary miliary tuberculosis, tuberculous meningitis and multiple intracranial tuberculomas is presented. While her pulmonary lesions and intracranial tuberculomas except one were healed with chemotherapy, one tuberculoma increased in size 1 month after starting chemotherapy. She was followed with dexamethasone treatment in addition to antituberculous therapy for 2 months. Then, the lesion was removed because it had increased in size in spite of appropriate chemotherapy. 相似文献
29.
AIM: To review the management of transposed teeth, and to illustrate the treatment options with four case reports. METHODS: The aetiology and management of transposed teeth are reviewed. Three management options are discussed: correcting the order of transposed teeth, maintaining the order of transposed teeth, and extraction of one of the transposed teeth. Methods of camouflaging transposed teeth are described in detail. The treatment options are illustrated with case reports. 相似文献
30.
OBJECTIVE: To report experience of gender (re)assignment in genotypic female (46XX) patients with congenital adrenal hyperplasia (f-CAH), a difficult and stressful experience if complicated with delayed presentation and inadvertent assignment. PATIENTS AND METHODS: Between 1983 and 2002, 70 patients with f-CAH were counselled for gender assignment. The age at diagnosis and operation, the degree of virilization, parental consanguinity, the gender preference of the families, and the factors governing the decision-making process were determined. RESULTS: Forty-one (59%) patients presented after the neonatal period. All parents had already assumed or were advised of a gender for their children, based on the suggestive appearance of the external genitalia. Consequently, 49 patients were reared as female and 21 as "male". Only nine of these "males" could be reassigned as females (mean age at presentation 7.87 months, sd 10.42). Twelve children had to be reared as "male"(mean age at presentation 55.8 months, sd 32.42) in compliance with the parents' and the study group's decision, and appropriate masculinizing reconstructive surgery was undertaken. The difference in the mean age of those reassigned as female and those who remained "male" was significant (P < 0.001). The parental consanguinity rate among the families was especially high in the 'male' patients. CONCLUSIONS It is extremely difficult to correct the gender of patients with f-CAH when they present at >2.5 years old. Furthermore, the delay in diagnosis and the male bias in choice of gender in our population might be a result of strong social pressures on families, influenced by cultural, traditional and economic factors. 相似文献