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81.
82.
Jones DG Liang X Stewart EL Noe RA Kallander LS Madauss KP Williams SP Thompson SK Gray DW Hoekstra WJ 《Bioorganic & medicinal chemistry letters》2005,15(13):3203-3206
Mifepristone is a non-selective antagonist of 3-oxosteroid receptors with both abortifacient and anti-endometriotic activities. Non-steroidal mimetics of mifepristone and progesterone are important templates for modulation of the progesterone receptor (PR). For our PR program, we sought an unexplored, synthetically accessible non-steroidal mimetic of mifepristone, suitable for parallel synthesis of analogues. Docking of compounds into a PR homology model identified 4-substituted pyrazolines, which, when synthesized and tested, exhibited functional antagonism of PR. 相似文献
83.
Gregory KE Ono RN Charbonneau NL Kuo CL Keene DR Bächinger HP Sakai LY 《The Journal of biological chemistry》2005,280(30):27970-27980
Biochemical and biophysical methods are used to show that BMP-7 is secreted as a stable complex consisting of the processed growth factor dimer noncovalently associated with its two prodomain propeptide chains and that the BMP-7 complex is structurally similar to the small transforming growth factor beta (TGFbeta) complex. Because the prodomain of TGFbeta interacts with latent TGFbeta-binding proteins, a family of molecules homologous to the fibrillins, the prodomain of BMP-7 was tested for binding to fibrillin-1 or to LTBP-1. The BMP-7 prodomain and BMP-7 complex, but not the separated growth factor dimer, interact with N-terminal regions of fibrillin-1. This interaction may target the BMP-7 complex to fibrillin microfibrils in the extracellular matrix. Immunolocalization of BMP-7 in tissues like the kidney capsule and skin reveals co-localization with fibrillin. However, BMP-7 immunolocalization in other tissues known to be active sites for BMP-7 signaling is not apparent, suggesting that immunolocalization of BMP-7 in certain tissues represents specific extracellular storage sites. These studies suggest that the prodomains of TGFbeta-like growth factors are important for positioning and concentrating growth factors in the extracellular matrix. In addition, they raise the possibility that prodomains of other TGFbeta-like growth factors interact with fibrillins and/or LTBPs and are also targeted to the extracellular matrix. 相似文献
84.
Cristina T Fonseca Daniela M Amaral Márcia G Ribeiro Izabel CR Beserra Marília M Guimarães 《BMC endocrine disorders》2005,5(1):1-6
Background
The prevalence of diabetes mellitus is higher in individuals with Down syndrome (DS) than in the general population; it may be due to the high prevalence of obesity presented by many of them. The aim of this study was to evaluate the insulin resistance (IR) using the HOMA (Homeostasis Model Assessment) method, in DS adolescents, describing it according to the sex, body mass index (BMI) and pubertal development.Methods
15 adolescents with DS (8 males and 7 females) were studied, aged 10 to 18 years, without history of disease or use of medication that could change the suggested laboratory evaluation. On physical examination, the pubertal signs, acanthosis nigricans (AN), weight and height were evaluated. Fasting plasma glucose and insulin were analysed by the colorimetric method and RIA-kit LINCO, respectively. IR was calculated using the HOMA method. The patients were grouped into obese, overweight and normal, according to their BMI percentiles. The EPIINFO 2004 software was used to calculate the BMI, its percentile and Z score.Results
Five patients were adults (Tanner V or presence of menarche), 9 pubertal (Tanner II – IV) and 1 prepubertal (Tanner I). No one had AN. Two were obese, 4 overweight and 9 normal. Considering the total number of patients, HOMA was 1.7 ± 1.0, insulin 9.3 ± 4.8 μU/ml and glucose 74.4 ± 14.8 mg/dl. The HOMA values were 2.0 ± 1.0 in females and 1.5 ± 1.0 in males. Considering the nutritional classification, the values of HOMA and insulin were: HOMA: 3.3 ± 0.6, 2.0 ± 1.1 and 1.3 ± 0.6, and insulin: 18.15 ± 1.6 μU/ml, 10.3 ± 3.5 μU/ml and 6.8 ± 2.8 μU/ml, in the obese, overweight and normal groups respectively. Considering puberty, the values of HOMA and insulin were: HOMA: 2.5 ± 1.3, 1.4 ± 0.6 and 0.8 ± 0.0, and insulin: 13.0 ± 5.8 μU/ml, 7.8 ± 2.9 μU/ml and 4.0 ± 0.0 μU/ml, in the adult, pubertal and prepubertal groups respectively.Conclusion
The obese and overweight, female and adult patients showed the highest values of HOMA and insulin. 相似文献85.
Charbonneau NL Ono RN Corson GM Keene DR Sakai LY 《Birth defects research. Part C, Embryo today : reviews》2004,72(1):37-50
Growth factors, potent regulators of cell differentiation, tissue morphogenesis, tissue homeostasis, and cellular response to injury, reside in the extracellular matrix. Genetic evidence in humans and mice as well as biochemical data implicate fibrillins and LTBPs in the extracellular control of TGFbeta and BMP signaling. Fibrillins and LTBPs form tissue-specific and temporally regulated microfibril networks. In the developing embryo, three fibrillins and four LTBPs contribute molecular heterogeneity to microfibril networks, and provide different templates upon which TGFbeta-related growth factors can be positioned. By accommodating this molecular heterogeneity, microfibril architecture can orchestrate a variety of different signals in very specific tissue locations. Human fibrillinopathies display a broad phenotypic spectrum from tall to short stature, from hypermobile joints to joint contractures and stiffness, and from severe to mild or no cardiovascular manifestations. A spectrum of growth factor dysregulation may be caused by differential effects of mutations in fibrillins on microfibril architecture, thus altering appropriate targeting or positioning of growth factors within microfibril networks. Growth factor dysregulation may help to explain the broad phenotypic spectrum of the fibrillinopathies. 相似文献
86.
Quality assurance of recombinant protein drugs concerning identity and purity represents a difficult task, in particular, when post-translational modifications lead to a heterogeneous mixture of biomolecules. We chose Neorecormon (rh-EPO, Roche) for our studies to demonstrate the efficiency of two-dimensional electrophoresis (2-DE) to analyse post-translationally modified recombinant drugs. More than 40 protein spots in the range from isoelectric point (pI) 3.5-4.5 and 32-45 kDa could be separated. Enzymatic deglycosylation revealed that the heterogeneity of the protein pattern is mainly caused by variations in glycosylation. In comparison to the separately performed isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, as requested by the European Pharmacopoeia, we see a great synergy to use 2-DE for the analysis of rh-EPO. A by far higher resolution can be achieved, allowing an improved differentiation of the various rh-EPO glycoforms. Sequential deglycosylation of sialic acids, N-glycosides and the O-glycoside lead to significant shifts both in apparent relative molecular mass and pI. Comparing the 2-DE patterns of rh-EPO before and after deglycosylation allows on the one hand valuable information to be gained on the glycosylation of the recombinant protein and shows on the other hand how significantly the 2-DE protein pattern can be influenced by the glycosylation. As the equipment for the performance of 2-DE has improved significantly over the last decade, we see 2-DE as a reliable method, which should be approved for the routine quality assurance of recombinant drugs and also recommended for the European Pharmacopoeia. 相似文献
87.
Interspecific differences in responsiveness to temperature, photoperiod, soil salinity, and soil moisture confirm the hypothesis that abiotic factors differentially affect the germination of salt marsh plants. In growth chamber experiments, four of eight annual species responded to small differences in temperature or photoperiod. Increasing soil salinity decreased the final proportion of seeds germinating and slowed germination for each of the seven species tested. Higher soil moisture increased the proportion germinating of five species and germination speed of all seven species. Salinity and moisture interacted to affect the proportion germinating of five species and germination speed of all seven species. Although the abiotic factor with the largest effect on germination varied among species, more species responded to, and the magnitudes of the responses were larger for, soil salinity than for the other abiotic factors. These germination tests partially explained interspecific differences in the timing of germination in the field. Patterns of Hutchinsia procumbens, Lythrum hyssopifolium, Parapholis incurva, and possibly Lasthenia glabrata ssp. coulteri germination in response to a nonseasonal rainfall could be explained by their response to salinity, temperature, or photoperiod. Fine-scale differences in the timing of establishment within the typical germination window and spatial distributions along salinity and moisture gradients were not explained. 相似文献
88.
Using circulant symmetry to model featureless objects 总被引:1,自引:0,他引:1
89.
Success of argon laser therapy as a therapeutic modality for port wine stains has been correlated with the degree of vascular congestion within the lesions. Epinephrine causes vasoconstriction and erythrocyte stasis within normally innervated vessels. We tested the hypothesis that subcutaneous injection of epinephrine would cause vasoconstriction, altered hemodynamics, and increased red cell mass in port wine stains and thus allow more directed and less nonspecific damage and a better cosmetic result. Two clinically similar and adjacent areas within port wine stains were biopsied from 10 patients following subcutaneous injection of either Xylocaine or Xylocaine with epinephrine. Erythrocytes within vessels of the superficial cutaneous vascular plexus were increased in areas pretreated with Xylocaine plus epinephrine (55.3 versus 45.9 percent; p less than 0.09). This increase was seen in 9 of 10 patients studied (p less than 0.05). Epinephrine appears to increase erythrocytes within ectatic vessels of port wine stains and thus would likely improve laser energy absorption and cosmetic results. 相似文献
90.