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101.
Georgsson J Sköld C Plouffe B Lindeberg G Botros M Larhed M Nyberg F Gallo-Payet N Gogoll A Karlén A Hallberg A 《Journal of medicinal chemistry》2005,48(21):6620-6631
Two 1,3,5-trisubstituted aromatic scaffolds intended to serve as gamma-turn mimetics have been synthesized and incorporated in five pseudopeptide analogues of angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe), replacing Val-Tyr-Ile, Val-Tyr, or Tyr-Ile. All the tested compounds exhibited nanomolar affinity for the AT2 receptor with the best compound (3) having a K(i) of 1.85 nM. Four pseudopeptides were AT2 selective, while one (5) also exhibited good affinity for the AT1 receptor (K(i) = 30.3 nM). This pseudopeptide exerted full agonistic activity in an AT2 receptor induced neurite outgrowth assay but displayed no agonistic effect in an AT1 receptor functional assay. Molecular modeling, using the program DISCOtech, showed that the high-affinity ligands could interact similarly with the AT2 receptor as other ligands with high affinity for this receptor. A tentative agonist model is proposed for AT2 receptor activation by angiotensin II analogues. We conclude that the 1,3,5-trisubstituted benzene rings can be conveniently prepared and are suitable as gamma-turn mimics. 相似文献
102.
Khalak HG Wakil SM Imtiaz F Ramzan K Baz B Almostafa A Hagos S Alzahrani F Abu-Dhaim N Abu Safieh L Al-Jbali L Al-Hamed MS Monies D Aldahmesh M Al-Dosari MS Kaya N Shamseldin H Shaheen R Al-Rashed M Hashem M Al-Tassan N Meyer B Alazami AM Alkuraya FS 《Genetics in medicine》2012,14(5):515-519
PurposeCopy number variants are an important source of human genome diversity. The widespread distribution of hemizygous copy number variants in the DNA of healthy humans suggests that haploinsufficiency is largely tolerated. However, little is known about the extent to which corresponding nullizygosity (two-copy deletion) is similarly tolerated.MethodsWe analyzed a cohort of first cousin unions to enrich for shared parental hemizygous events and tested their Mendelian inheritance in offspring.ResultsAnalysis of autozygous DNA blocks (autozygome) in the offspring not only proved an efficient method of mapping “dispensable” DNA but also revealed potential selective bias against the occurrence of nullizygous changes. This bias was not restricted to genic copy number variants and was not accounted for by a high rate of miscarriages.ConclusionsThe autozygome is an efficient way to map dispensable segments of DNA and may reveal selective bias against nullizygosity in healthy individuals.Genet Med 2012:14(5):515–519 相似文献
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Mostafazadeh A Saravi M Niaki HA Drabbels J Gholipour HM Minagar M Mosavi E Jalali F Bijani A 《Iranian journal of allergy, asthma, and immunology》2011,10(1):11-19
Coronary atherosclerotic disease is one of the most endangering health disorder worldwide. This study was designed to investigate the correlation between HLA-DR1 alleles and circulating Th1/Th2 type cytokines in coronary atherosclerosis. By Elisa, Th1/Th2 type cytokines were determined in serum samples of 31 subjects with unstable angina, 27 subjects with chronic stable angina and 24 individuals as normal control. By SSP-PCR, more than 100 alleles of HLA-DRBeta1 were typed in 24 subjects who had skewed serum levels of Th1/Th2 type cytokines. Lipid profiles were determined by the routine methods of clinical laboratory in all subjects. The mean serum concentration of IL-10 in normal control subjects was higher in comparison to the patient groups.0.33±0.59 pg/ml versus 0.064±0.3 pg/ml in unstable angina pectoris group (p<0.028) and 0.22±0.6 pg/ml in chronic stable subjects. There was no statistically significant difference among the groups in serum levels of other desired cytokines (IFN-Gamma, IL-4). 33.33% of normal control subjects were HLA-DR16 positive whereas none of the subjects with chronic stable angina or individuals with unstable angina pectoris was positive for this antigen. The mean concentration of serum LDL-cholesterol in normal control group was high 142.046±35.40 (pg/ml).This preliminary study shows that the atherogenic effect of the LDL- cholesterol may be dampened by HDL-cholesterol through anti inflammatory cytokine IL-10 and HLA-DR16, a phenomenon interpretable via immunological homunculus theory. 相似文献
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Serdar E. Bulun Hiroki Utsunomiya Zhihong Lin Ping Yin You-Hong Cheng Mary E. Pavone Hideki Tokunaga Elena Trukhacheva Erkut Attar Bilgin Gurates Magdy P. Milad Edmond Confino Emily Su Scott Reierstad Qing Xue 《Molecular and cellular endocrinology》2009,300(1-2):104
Endometriosis is a common and chronic disease characterized by persistent pelvic pain and infertility. Estradiol is essential for growth and inflammation in endometriotic tissue. The complete cascade of steroidogenic proteins/enzymes including aromatase is present in endometriosis leading to de novo estradiol synthesis. PGE2 induces the expression of the genes that encode these enzymes. Upon PGE2 treatment, coordinate recruitment of the nuclear receptor SF-1 to the promoters of these steroidogenic genes is the key event for estradiol synthesis. SF-1 is the key factor determining that an endometriotic cell will respond to PGE2 by increased estradiol formation. The presence of SF-1 in endometriosis and its absence in endometrium is determined primarily by the methylation of its promoter. The key steroidogenic enzyme in endometriosis is aromatase encoded by a single gene because its inhibition blocks all estradiol biosynthesis. Aromatase inhibitors diminish endometriotic implants and associated pain refractory to existing treatments in affected women. 相似文献
109.
Xueshuang Mei Francesca Atturo Karin Wadin Sune Larsson Sumit Agrawal Hanif M. Ladak 《Upsala journal of medical sciences》2013,118(3):131-142
AbstractBackground: The Uppsala collection of human temporal bones and molds is a unique resource for education and international research collaboration. Micro-computerized tomography (micro-CT) and synchrotron imaging are used to investigate the complex anatomy of the inner ear. Impaired microcirculation is etiologically linked to various inner ear disorders, and recent developments in inner ear surgery promote examination of the vascular system. Here, for the first time, we present three-dimensional (3D) data from investigations of the major vascular pathways and corresponding bone channels.Methods: We used the archival Uppsala collection of temporal bones and molds consisting of 324 inner ear casts and 113 macerated temporal bones. Micro-CT was used to investigate vascular bone channels, and 26 fresh human temporal bones underwent synchrotron radiation phase contrast imaging (SR-PCI). Data were processed by volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and soft tissue analyses.Results: Micro-CT with 3D rendering was superior in reproducing the anatomy of the vascular bone channels, while SR-PCI replicated soft tissues. Arterial bone channels were traced from scala vestibuli (SV) arterioles to the fundus, cochlea, and vestibular apparatus. Drainage routes along the aqueducts were examined.Conclusion: Human inner ear vessels are difficult to study due to the adjoining hard bone. Micro-CT and SR-PCI with 3D reconstructions revealed large portions of the micro-vascular system in un-decalcified specimens. The results increase our understanding of the organization of the vascular system in humans and how altered microcirculation may relate to inner ear disorders. The findings may also have surgical implications. 相似文献
110.
Maryam Khojasteh-Fard Milad Abolhalaj Parvin Amiri Majid Zaki Zahra Taheri Mostafa Qorbani Javad Tavakkoly Bazzaz Mahsa M. Amoli 《Disease markers》2012,33(6):289-293
Objective: Both adaptive and innate immune systems are involved in coronary artery disease (CAD). The aim of this study was to evaluate TH17 cytokines expression profiles in un-stimulated peripheral blood lymphocytes (PBMCs) of patients with coronary artery disease. Methods: Expression profiles of IL-17, IL-23, and TGF-β1 were determined in individuals with and without CAD using Real-time PCR. Results: A significant decrease in IL-23 gene expression in un-stimulated PBMCs of patients with CAD compared to those without CAD was found (p=0.003, OR=0.045, 95% CI: 0.006–0.355). Conclusion: Our data reinforce the potential role of the IL-23 as a critical regulatory molecule that bridges the innate and adaptive arms of the immune system in the complex mechanisms associated with the development of atherosclerosis. 相似文献