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排序方式: 共有261条查询结果,搜索用时 187 毫秒
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Bone scintigraphy in the reflex sympathetic dystrophy syndrome 总被引:1,自引:0,他引:1
45.
Henrik B Mortensen Peter GF Swift Reinhard W Holl P Hougaard Lars Hansen Hilde Bjoerndalen Carine E De Beaufort Michael Knip and Hvidoere Study Group on Childhood Diabetes 《Pediatric diabetes》2010,11(4):218-226
HB Mortensen, PGF Swift, RW Holl, P Hougaard, L Hansen, H Bjoerndalen, CE de Beaufort, M Knip. Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age, ketoacidosis, HLA status, and autoantibodies on residual beta‐cell function and glycemic control 12 months after diagnosis. Objective: To identify predictors of residual beta‐cell function and glycemic control during the first 12 months after the diagnosis of type 1 diabetes (T1D). Subjects and Methods: Clinical information and blood samples were collected from 275 children. HbA1c, antibodies, HLA typing and mixed meal‐stimulated C‐peptide levels 1, 6, and 12 months after diagnosis were analyzed centrally. Results: Mean age at diagnosis was 9.1 yr. DKA with standard bicarbonate <15 mmol/L was associated with significantly poorer residual beta‐cell function 1 (p = 0.004) and 12 months (p = 0.0003) after diagnosis. At 12 months, the decline in stimulated C‐peptide levels compared with the levels at 1 month was 69% in the youngest age group and 50% in patients 10 yr and above (p < 0.001). Stimulated C‐peptide at 12 months was predicted by younger age (p < 0.02) and bicarbonate levels at diagnosis (p = 0.005), and by stimulated C‐peptide (p < 0.0001), postmeal blood glucose (p = 0.0004), insulin antibodies (IA; p = 0.02) and glutamic acid decarboxylase antibodies (GADA; p = 0.0004) at 1 month. HbA1c at 12 months was predicted by HbA1c at diagnosis (p < 0.0001), GADA at 1 month (p = 0.01), and non‐white Caucasian ethnicity (p = 0.002). Conclusions: Younger age, ketoacidosis at diagnosis, and IA and GADA 1 month after diagnosis were the strongest explanatory factors for residual beta‐cell function at 12 months. Glycemic control at 12 months was influenced predominantly by ethnicity, HbA1c at diagnosis, and GADA at 1 month. 相似文献
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Background and purpose:
The glucagon-like peptide-1 receptor (GLP-1R) belongs to Family B of the G protein-coupled receptor superfamily and is a target for treatment of type 2 diabetes. Family B G protein-coupled receptors contain a putative N-terminal signal peptide, but its role in receptor synthesis and trafficking are unclear. Further, the signal peptide is not cleaved in at least one family member.Experimental approach:
We examined receptor glycosylation and the role of the signal peptide in GLP-1R synthesis and trafficking using constructs containing epitope tags at the N- and/or C-terminus and in which the signal peptide sequence was either present or absent.Key results:
The signal peptide was absolutely required for GLP-1R synthesis but could be substituted to some extent by increasing positive charge in the N-terminal region of the receptor flanking the signal peptide. The signal peptide is cleaved during synthesis and processing of the receptor. An enhanced GFP-epitope tag at the N-terminus of the receptor permitted synthesis of the receptor but blocked signal peptide cleavage and prevented trafficking to the plasma membrane. Cleavage site mutation allowed synthesis of a full-length receptor, blocked signal peptide cleavage and caused retention within the endoplasmic reticulum.Conclusions and implications:
Signal peptide cleavage was not essential for receptor synthesis but was obligatory for processing and trafficking of receptors to the plasma membrane. Further, the GLP-1R is subject to N-linked glycosylation and only the mature, fully glycosylated form of the receptor is present in the plasma membrane. Inhibition of glycosylation prevents processing and cell surface expression of the GLP-1R. 相似文献47.
S Khom B Strommer J Ramharter T Schwarz C Schwarzer T Erker GF Ecker J Mulzer S Hering 《British journal of pharmacology》2010,161(1):65-78
BACKGROUND AND PURPOSE
Subunit-specific modulators of γ-aminobutyric acid (GABA) type A (GABAA) receptors can help to assess the physiological function of receptors with different subunit composition and also provide the basis for the development of new drugs. Valerenic acid (VA) was recently identified as a β2/3 subunit-specific modulator of GABAA receptors with anxiolytic potential. The aim of the present study was to generate VA derivatives as novel GABAA receptor modulators and to gain insight into the structure–activity relation of this molecule.EXPERIMENTAL APPROACH
The carboxyl group of VA was substituted by an uncharged amide or amides with different chain length. Modulation of GABAA receptors composed of different subunit compositions by the VA derivatives was studied in Xenopus oocytes by means of the two-microelectrode voltage-clamp technique. Half-maximal stimulation of GABA-induced chloride currents (IGABA) through GABAA receptors (EC50) and efficacies (maximal stimulation of IGABA) were estimated. Anxiolytic activity of the VA derivatives was studied in mice, applying the elevated plus maze test.KEY RESULTS
Valerenic acid amide (VA-A) displayed the highest efficacy (more than twofold greater IGABA enhancement than VA) and highest potency (EC50= 13.7 ± 2.3 µM) on α1β3 receptors. Higher efficacy and potency of VA-A were also observed on α1β2γ2s and α3β3γ2s receptors. Anxiolytic effects were most pronounced for VA-A.CONCLUSIONS AND IMPLICATIONS
Valerenic acid derivatives with higher efficacy and affinity can be generated. Greater in vitro action of the amide derivative correlated with a more pronounced anxiolytic effect in vivo. The data give further confidence in targeting β3 subunit containing GABAA receptors for development of anxiolytics. 相似文献48.
Wang Minjiao Qian Yifeng Zhao Hanjiang Zhu Min Yu Hongbo Shen Steve GF. 《Clinical oral investigations》2022,26(12):7083-7093
Clinical Oral Investigations - To evaluate postoperative mandibular stability and condylar changes in patients with mandibular hypoplasia and preoperative condylar resorption (CR) undergoing... 相似文献
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Comparison of assays for anti-HBc in blood donors 总被引:5,自引:0,他引:5
Testing for anti-HBc has been recommended for use as a paradoxical or surrogate marker of carriers of non-A, non-B hepatitis. Serial sampling on a pool of 35,600 donors was done and those donors found to be repeatedly reactive by EIA method were rested using RIA methodology. Of 1367 donors found to be repeatedly reactive by EIA method, only 984 were confirmed by RIA. Those found to be reactive by EIA only were allowed to donate blood again, with only three of them becoming positive by both EIA and RIA on subsequent donations. The majority of these donors (107 out of 151) reverted to EIA negative status. Therefore, the finding of a positive anti-HBc by EIA method that could not be repeated by RIA method is not an early reproducible sign of anti-HBc reactive status. 相似文献