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11.
Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations 总被引:9,自引:1,他引:9
Meyer J; Sudbeck P; Held M; Wagner T; Schmitz ML; Bricarelli FD; Eggermont E; Friedrich U; Haas OA; Kobelt A; Leroy JG; Van Maldergem L; Michel E; Mitulla B; Pfeiffer RA; Schinzel A; Schmidt H; Scherer G 《Human molecular genetics》1997,6(1):91-98
It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
12.
Cenk Can Buket Demirci Ay?egül Uysal Yasemin Delen Ak?ay Sezen Ko?ay 《Pharmacological research》2003,48(3):223-230
We examined the effects of the phenothiazine derivative, chlorpromazine on thoracic aortic endothelial cell histology (14 h after LPS challenge) in a model of endotoxic shock in rats. Since excessive formation of tumor necrosis factor-alpha (TNF-alpha) and oxygen-derived free radicals contribute to endothelial injury in endotoxemia, we also evaluated the effect of the drug on the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase in liver tissue in this model and tried to find out whether this possible effect was associated with a change in serum TNF-alpha levels (measured 90 min after chlorpromazine administration). Endotoxemia was induced by a single i.p. injection of lipopolysaccharide (LPS) (5 mg kg(-1) in 1.5 ml of saline; LPS from Escherichia coli serotype 055:B5, L-2880, Sigma Chemical Company). Electron microscopic evaluation of the aortas revealed that chlorpromazine (administered 30 min prior to LPS challenge), in smaller doses (3 mg kg(-1)) ameliorated the endothelial cell injury caused by LPS, whereas it caused deterioration of endothelial cell morphology in higher doses (10 and 25 mg kg(-1)). Chlorpromazine administration caused a significant reduction in serum TNF-alpha levels, which was correlated well with an increase in SOD activity in all drug doses (3, 10 and 25 mg kg(-1)). Catalase activity was increased only in the 25 mg kg(-1) chlorpromazine group. 相似文献
13.
Effect of genetic modification of acute inflammatory responsiveness on tumorigenesis in the mouse 总被引:1,自引:3,他引:1
14.
15.
3-Aminobenzamide,a Poly ADP Ribose Polymerase Inhibitor,Attenuates Renal Ischemia/Reperfusion Injury
Introduction. This study was designed to investigate whether 3-amino benzamide (3-AB), a poly (ADP-ribose) polymerase (PARP) inhibitor, has a protective effect on kidney injury induced by renal ischemia/reperfusion (I/R) by decreasing oxidative and nitrosative stress on renal dysfunction and injury. Materials and Methods. Thirty-two male Sprague-Dawley rats were divided into four groups: sham-operated, sham-operated + 3-AB, I/R, I/R + 3-AB. Rats were given 3-AB (100 mg/kg/day ip) 14 days prior to I/R. I/R and I/R + 3-AB groups underwent 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood were obtained for evaluation. Superoxide dismutase, glutathione peroxidase, malondialdehide, protein carbonyl content, and nitrite/nitrate level (NOx) were determined in the renal tissue. Serum creatinine (SCr), blood urea nitrogen (BUN), and aspartate aminotransferase (AST) were determined in the blood. Additionally, renal sections were used for histological grade of renal injury. Results. 3-AB significantly reduced the I/R-induced increases in SCr, BUN, and AST. In addition, 3-AB markedly reduced elevated oxidative stress product, restored decreased antioxidant enzymes, and attenuated histological alterations. Moreover, 3-AB attenuated the tissue NOx levels, indicating reduced NO production. Conclusions. 3-AB has beneficial effect on renal glomerular and tubular dysfunction in rats' kidneys subjected to I/R injury. Moreover, 3-AB has ameliorating effect on both oxidative stress and nitrosative stress of the kidneys, which correlated with histopathological evaluation. 相似文献
16.
17.
Uysal Bora 《European journal of orthopaedic surgery & traumatology : orthopedie traumatologie》2018,28(4):757-757
European Journal of Orthopaedic Surgery & Traumatology - 相似文献
18.
19.
Battal Tahsin Somuk Sema Koc Omer Ates Göksel Göktas Harun Soyalic Ismail Onder Uysal 《Acta oto-laryngologica》2016,136(11):1168-1172
Conclusion: A significant association was found of oropharyngeal tularemia with SLC11A1 allele polymorphism (INT4?G/C) and MBL2 C?+?4T (P/Q). These results indicate C allele and Q allele might be a risk factor for the development of oropharyngeal tularemia.Aim: This study aimed to investigate the relationship of SLC11A1, MBL, and P2X7 gene polymorphism with oropharyngeal tularemia.Methods: The study included totally 120 patients who were diagnosed with oropharyngeal tularemia. Frequencies of polymorphisms in the following genes were analyzed both in the patient and control groups in the study: SLC11A1 (5’(GT)n Allele 2/3, Int4?G/C, 3’ UTR, D543N G/A), MBL (MBL2 C?+?4T (P/Q), and P2X7 (?762 C/T and 1513 A/C).Results: Among all polymorphisms that were investigated in this study, SLC11A1 gene showed a significance in the distriburtion of polymorphism allelle frequency at the INT4 region. Frequency of C allele was 54 (28%) in patients with oropharyngeal tularemia, and 31 (13%) in the control group (p?=?0.006 and OR = 1.96 (1.21–3.20)). An association was detected between MBL2 C?+?4T (P/Q) gene polymorphism and oropharyngeal tularemia (p?0.005 and OR?=?0.30 (0.19–0.48)). No significant relation was found between P2X7 (?762 C/T and 1513 A/C) gene polymorphism and oropharyngeal tularemia in this study (p?>?0.05). 相似文献
20.
Glutathione S-transferase-pi in malignant tissues and plasma of human colorectal and gastric cancers 总被引:7,自引:0,他引:7
Doğru-Abbasoğlu S Mutlu-Türkoğlu U Türkoğlu S Erbil Y Barbaros U Uysal M Aykaç-Toker G 《Journal of cancer research and clinical oncology》2002,128(2):91-95
PURPOSE: In this study, 16 paired samples of colorectal and gastric cancers and adjacent non-neoplastic tissues were analysed for the determination of glutathione S-transferase (GST) activities and the expression of GST-pi. METHODS: Western blotting procedure as well as plasma GST-pi levels were used. RESULTS: GST activities were found to be increased in malignant tissues of patient compared with adjacent normal tissues. A significant correlation was detected between GST activity and GST-pi expression in malignant tissues of patients. Plasma GST-pi levels increased in patients compared to aged-matched control subjects. When the patients were grouped according to TNM stage, GST-pi expression in malignant tissues as well as plasma GST-pi levels were higher in patients with more advanced tumor stages. CONCLUSIONS: Our results indicate that GST-pi expression in malignant tissues and plasma GST-pi levels in human colorectal and gastric cancers increased depending on the stages of tumor. 相似文献