| 1. |
|
|
| 2. |
|
|
| 3. |
- Branham, Kari, et al.
(författare)
-
Mutations in RPGR and RP2 Account for 15% of Males with Simplex Retinal Degenerative Disease
- 2012
-
Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 53:13, s. 8232-8237
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine the proportion of male patients presenting simplex retinal degenerative disease (RD: retinitis pigmentosa [RP] or cone/cone-rod dystrophy [COD/CORD]) with mutations in the X-linked retinal degeneration genes RPGR and RP2. METHODS. Simplex males were defined as patients with no known affected family members. Patients were excluded if they had a family history of parental consanguinity. Blood samples from a total of 214 simplex males with a diagnosis of retinal degeneration were collected for genetic analysis. The patients were screened for mutations in RPGR and RP2 by direct sequencing of PCR-amplified genomic DNA. RESULTS. We identified pathogenic mutations in 32 of the 214 patients screened (15%). Of the 29 patients with a diagnosis of COD/CORD, four mutations were identified in the ORF15 mutational hotspot of the RPGR gene. Of the 185 RP patients, three patients had mutations in RP2 and 25 had RPGR mutations (including 12 in the ORF15 region). CONCLUSIONS. This study represents mutation screening of RPGR and RP2 in the largest cohort, to date, of simplex males affected with RP or COD/CORD. Our results demonstrate a substantial contribution of RPGR mutations to retinal degenerations, and in particular, to simplex RP. Based on our findings, we suggest that RPGR should be considered as a first tier gene for screening isolated males with retinal degeneration. (Invest Ophthalmol Vis Sci. 2012;53:8232-8237) DOI:10.1167/iovs.12-11025
|
|
| 4. |
- Caglar, K, et al.
(författare)
-
Serum fetuin-a concentration and endothelial dysfunction in chronic kidney disease
- 2008
-
Ingår i: Nephron. Clinical practice. - : S. Karger AG. - 1660-2110. ; 108:3, s. C233-C240
-
Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Defective endothelial function, an initial step in the development of atherosclerotic plaque, is prevalent in moderate to advanced chronic kidney disease (CKD). In this study, the investigators hypothesized that fetuin-A, a calcification inhibitor, is a novel risk factor for the development of endothelial dysfunction in patients. <i>Methods:</i> 198 nondiabetic patients with a mean age of 44.0 ± 12.4 years and with different stages of CKD were studied. In addition to a detailed metabolic panel, flow-mediated dilatation assessed by high-resolution brachial ultrasonography was performed to determine endothelial dysfunction. Carotid intima-media thickness was also estimated by ultrasonography. Serum fetuin-A concentrations were determined by using a human ELISA method. <i>Results:</i> Endothelial dysfunction was observed in all stages (1–5) of CKD and worsened in parallel to the reduction in estimated glomerular filtration rate. Serum fetuin-A concentrations were also found to be decreased in all but stage 1 CKD. On multiple regression analysis, endothelial dysfunction was independently associated with fetuin-A (β = 0.745, p < 0.001) and intact parathyroid hormone concentrations (β = –0.216, p < 0.001). <i>Conclusion:</i> These data in a selected cohort of CKD patients indicate that fetuin-A may be one of the contributing factors for the development of endothelial dysfunction in CKD patients.
|
|
| 5. |
|
|
| 6. |
- Gawel, Danuta, et al.
(författare)
-
A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
- 2019
-
Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs. Methods: The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs. Results: We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model. Conclusions: Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Yilmaz, MI, et al.
(författare)
-
Improving proteinuria, endothelial functions and asymmetric dimethylarginine levels in chronic kidney disease: ramipril versus valsartan
- 2007
-
Ingår i: Blood purification. - : S. Karger AG. - 1421-9735 .- 0253-5068. ; 25:4, s. 327-335
-
Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> The aim of this study was to find out whether the beneficial effects of the renin-angiotensin-aldosterone system (RAS) blockage in chronic kidney disease (CKD) has any relation with the alteration of asymmetric dimethylarginine (ADMA) levels. <i>Methods:</i> Sixty-six nondiabetic patients with CKD and proteinuria and 36 healthy subjects were enrolled. Patients were treated with either ramipril 5 mg daily or valsartan 160 mg daily for 3 months. Proteinuria, ADMA, symmetric dimethyl arginine (SDMA), flow-mediated dilatation (FMD) and HOMA index measurements were performed both before and after the treatment. <i>Results:</i> ADMA, SDMA, hsCRP levels, HOMA index and proteinuria of patients were significantly higher (p < 0.001 for all) and FMD, <i>L</i>-arginine and <i>L</i>-arginine/ADMA ratio in CKD were significantly lower than controls. According to the multiple regression analysis, proteinuria levels were independently related to ADMA and SDMA levels. <i>Conclusion:</i> Both drugs were equally effective in reducing elevated ADMA levels and improving endothelial dysfunction in CKD patients.
|
|
| 16. |
|
|
| 17. |
- Yilmaz, MI, et al.
(författare)
-
Predictors of carotid artery intima-media thickness in chronic kidney disease and kidney transplant patients without overt cardiovascular disease
- 2010
-
Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 31:3, s. 214-221
-
Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Carotid intima-media thickness (IMT) assessed using ultrasonography is a widely used marker of atherosclerosis. In the largest study to date of IMT and chronic kidney disease (CKD), we assessed correlates of IMT in CKD patients with a wide range of renal dysfunction, and also investigated what happens to IMT following renal transplantation. <i>Methods:</i> We studied 406 patients with different stages of nondiabetic CKD (50% males, 46 ± 12 years), and 58 kidney transplant recipients (27 ± 6 years), testing relationships between IMT, assessed by ultrasonography, and selected biomarkers. <i>Results:</i> Despite a lack of overt CVD, patients had significantly higher IMT as compared to controls (0.9 [0.7–1.0] vs. 0.6 [0.4–0.7] mm; p > 0.001). Furthermore, in multivariate analysis IMT was independently associated with CKD stage, mean arterial pressure (MAP) and calcium-phosphate product, but not with Framingham risk factors. Following kidney transplantation, IMT decreased rapidly, reaching levels comparable to those in the controls within 90 days. In a time-dependent multivariate analysis, this decrease was predicted by changes in GFR, MAP, and uric acid levels. <i>Conclusion:</i> Our data does not exclude IMT as a predictor of mortality in CKD, but suggests that other etiologies than atherosclerosis may be more important in determining IMT levels in the population with CKD.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
