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Functional studies and rare variant screening of SLC1A1/EAAC1 in males with obsessive-compulsive disorder 总被引:1,自引:0,他引:1
Veenstra-Vanderweele J Xu T Ruggiero AM Anderson LR Jones ST Himle JA Kennedy JL Richter MA Hanna GL Arnold PD 《Psychiatric genetics》2012,22(5):256-260
Several studies have found that the neuronal glutamate transporter gene SLC1A1/EAAC1 is associated with obsessive-compulsive disorder (OCD), with a stronger association in males. Previous studies have primarily focused on common single-nucleotide polymorphisms, rather than rare functional variants that are likely to have larger effects. We screened 184 males with OCD for rare variation in SLC1A1 exons; however, no new coding variation was found. When combined with previous screens, only one SLC1A1 amino acid variant has been detected among the 841 individuals screened, which is less than for other neurotransmitter transporter genes (P=0.0001). We characterized the function of the one SLC1A1 missense variant reported previously in OCD, Thr164Ala, and found that the Ala164 allele leads to decreased Vmax and Km (P<0.0001) in transfected human embryonic kidney cells. Further work will be necessary to understand the impact of this rare SLC1A1/EAAC1 Ala164 variant on neuronal function and circuitry relevant to OCD. 相似文献
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We present a rare case of fistulation of a dermoid cyst with the transverse colon. We illustrate how an infected dermoid cyst can be diagnosed as an appendix abscess although the management of these is quite different. The general surgeon should be aware of this as a differential diagnosis for an appendix abscess. 相似文献
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Amanda Hanna Jill Banks Denise A. Marston Richard J. Ellis Sharon M. Brookes Ian H. Brown 《Emerging infectious diseases》2015,21(5):879-882
Genetic sequences of a highly pathogenic avian influenza (H5N8) virus in England have high homology to those detected in mainland Europe and Asia during 2014. Genetic characterization suggests this virus is an avian-adapted virus without specific affinity for zoonoses. Spatio-temporal detections of H5N8 imply a role for wild birds in virus spread. 相似文献
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Maarten Albersen Loes Linsen Hanna Tinel Peter Sandner Koenraad Van Renterghem 《The journal of sexual medicine》2013,10(5):1268-1277
IntroductionOverall efficacy rates of phosphodiesterase type 5 inhibitors (PDE5‐i) for erectile dysfunction (ED) are 60–70%. PDE5‐i treatment failures currently have to resort to invasive treatment options for restoration of erectile function.AimsTo assess changes in the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase (PKG) pathway in human corpus cavernosum (HCC) of PDE5‐i nonresponders compared with healthy controls. To evaluate the effects of BAY 60‐4552, a stimulator of soluble guanylate cyclase (sGC), and vardenafil on relaxation of HCC strips from PDE5‐i nonresponders.Main Outcome MeasuresmRNA expression, morphological localization of the NO/cGMP/PKG pathway, and relaxant capacity of both compounds alone or combined. Analysis of variance, t‐test or Mann–Whitney test based upon number of groups and normality of data.MethodsHCC tissues were harvested after consent from individuals undergoing penile prosthesis implantation (patients) and potent patients undergoing transurethral surgery (healthy controls, needle biopsy). HCC tissues of patients were compared with those of healthy controls for the expression of mRNA coding for PDE5A, eNOS, PKGα1, PKG2, sGCα1, sGCα2, sGCβ1, sGCβ2, α‐smooth muscle actin (aSMA) and β‐actin by quantitative polymerase chain reaction (qPCR). The respective proteins were localized using immunofluorescence. Tissue strips of patients were precontracted with phenylepinephrine followed by incubation with 1 μM of either vardenafil or BAY 60‐4552, or both simultaneously.ResultsThe main targets in the NO/cGMP/sGC pathway were downregulated in PDE5‐i nonresponders. The pathway was morphologically located to HCC smooth muscle, of which the overall content was preserved in ED patients based on aSMA expression. BAY 60‐4552 and vardenafil have synergistic effects on relaxation of HCC of PDE5‐i nonresponders. The main limitation is the small amount of control tissue precluding functional testing on these samples.ConclusionDespite downregulation of the NO/cGMP/PKG pathway, combining BAY 60‐4552 with vardenafil significantly enhanced relaxation HCC strips of PDE5‐i nonresponders. 相似文献
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Various bone proteins and growth factors in specific concentrations are required for bone formation. If the body cannot produce sufficient quantities of these factors, bone trauma can be healed with an implant that includes the required factors in a carrier. This study was designed to evaluate various calcium salt candidates that can be used as carrier with reindeer bone protein extract to induce ectopic bone formation in the muscle pouch model of mouse. The bone protein extract was either impregnated into the disc form of carrier or mixed with carrier powder before implantation. The radiographic analysis indicated increased bone formation in all of the active groups containing the bone protein extract compared to the controls within 21 days follow-up. The highest bone formation was seen in the group with calcium sulfate with stearic acid where new bone and calcified cartilage were clearly visible. The greatest bone formation occurred in the groups that had bone protein extract readily available. This indicates that the bone forming factors in sufficient concentrations are required at the early stage of bone formation. The calcium sulfate with stearic acid was the most suitable and effective carrier for reindeer bone protein extract. 相似文献
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