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71.
OBJECTIVE: To use molecular genetic techniques to prenatally screen for aniridia. DESIGN: Case report. METHODS: DNA was extracted from cultured fibroblasts obtained through amniocentesis. Two mutation detection methods, Ava1 restriction digestion and single-strand conformational polymorphism electrophoresis, were used to screen the PAX6 gene. MAIN OUTCOME MEASURES: The results from the amniocentesis sample were compared with DNA obtained from the affected father, firstborn infant, and unaffected mother to determine whether the fetus carried the PAX6 mutation. RESULTS: DNA from the fetus demonstrated the same banding pattern as the affected father and firstborn infant. CONCLUSIONS: The fetus carried the mutated PAX6 allele and was predicted to develop aniridia. This was later confirmed when the child was born. This case report illustrates an important use of genetic mutation screening in the clinical setting. 相似文献
72.
Booth AP Anwar R Chen H Churchill AJ Jay J Polansky J Nguyen T Markham AF 《The British journal of ophthalmology》2000,84(7):722-726
AIMS: A number of genetic loci have been implicated in the pathogenesis of primary open angle glaucoma (POAG). The aim of this study was to identify the genetic cause of POAG in a large Scottish family and, if possible, offer genetic screening and advice to family members. METHODS: Family members were examined to determine their disease status. Base excision sequence scanning was carried out in order to test for the presence of a POAG causing mutation at known genetic loci. Direct DNA sequencing was performed in order to determine the mutation sequence. RESULTS: All family members of known affected disease status and two family members of unknown disease status were found to have a mutation in the TIGR gene. The mutation resulted in the substitution of a glycine residue with an arginine residue at codon 252 (Gly252Arg). No other sequence variations were present in any members of the family. CONCLUSION: The Gly252Arg mutation in the TIGR gene results in the development of POAG in this family. It was possible to identify younger, currently unaffected, members of the family who carry the mutation and who are therefore at a very high risk of developing POAG themselves. This is the first demonstration that Gly252Arg can be a disease causing mutation rather than a benign polymorphism. The possible pathogenic mechanisms and wider implications of the mutation are considered. 相似文献
73.
74.
75.
Dean GL Williams DI Churchill DR Fisher MJ 《American journal of respiratory and critical care medicine》2002,165(12):1670; author reply 1670
76.
Comparison of mortality risk for dialysis patients and cadaveric first renal transplant recipients in Ontario, Canada 总被引:8,自引:0,他引:8
Rabbat CG Thorpe KE Russell JD Churchill DN 《Journal of the American Society of Nephrology : JASN》2000,11(5):917-922
In population-based studies, renal transplantation has been shown to improve survival compared to dialysis patients awaiting transplantation in the United States. However, dialysis mortality in the United States is higher than in Canada. Whether transplantation offers a survival advantage in regions where dialysis survival is superior to that in the United States is uncertain. This study examines a cohort of 1156 patients who started end-stage renal disease (ESRD) therapy and were wait-listed for cadaveric renal transplantation in the province of Ontario, Canada between January 1, 1990 and December 31, 1994. Patients were followed from wait-listing for renal transplant (n = 1156), to cadaveric first renal transplant (n = 722), to death, or to study end (December 31, 1995). The annual crude mortality rates for wait-listed dialysis patients and transplanted patients were 5.0 and 3.4%, respectively. In Cox proportional hazards models, mortality in wait-listed patients was associated with increased age and diabetes, but not time from onset of ESRD to wait-listing. Factors associated with death following transplantation include older age, diabetes, and longer time spent on the waiting list before transplantation. In a time-dependent Cox regression model, the relative risk of death after transplantation compared to dialysis varied in a time-dependent manner. Covariates associated with increased risk included older age, diabetes, and time from onset of ESRD to wait-listing. The average relative risk (RR) of dying was 2.91 (95% confidence interval [CI], 1.34 to 6.32) in the first 30 d after transplantation, but was significantly lower 1 yr after transplantation (RR 0.25; 95% CI, 0.14 to 0.42), indicating a beneficial long-term effect when compared to wait-listed dialysis patients. This long-term benefit was most evident in subgroups of patients with diabetes (RR 0.38; 95% CI, 0.17 to 0.87) and glomerulonephritis (RR 0.13; 95% CI, 0.04 to 0.39) as the cause of ESRD. The survival advantage associated with renal transplantation is evident in this cohort of patients with a lower wait-listed dialysis mortality than that reported previously in the United States. The magnitude of the treatment effect is consistent across studies. 相似文献
77.
Norton KI Kattan M Rao JS Cleveland R Trautwein L Mellins RB Berdon W Boechat MI Wood B Meziane M Platzker AC;P 《AJR. American journal of roentgenology》2001,176(6):1553-1558
OBJECTIVE: We prospectively studied children with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 to determine the incidence of chronic radiographic lung changes (CRC) and to correlate these changes with clinical assessments. SUBJECTS AND METHODS: Between 1990 and 1997, we scored 3050 chest radiographs using a standardized form. Group I children (n = 201) were HIV-1-infected at enrollment. Group II children (n = 512) were enrolled prenatally or before 28 days postpartum and subsequently subdivided into group IIa (n = 86), children identified as HIV-1-infected; and group IIb (n = 426), those who were HIV-1-uninfected. CRC were defined as parenchymal consolidations or nodular disease lasting 3 months or more or increased bronchovascular markings or reticular densities lasting 6 months or more. Morbidity was assessed by CD4 counts, viral load, the presence of low oxygen saturation, wheezing, tachypnea, crackles, and clubbing. RESULTS: The cumulative incidence of chronic radiographic lung changes in HIV-1-infected children was 32.8% by 4 years old, with increased bronchovascular markings or reticular densities being most common. Chronic changes were associated with lower CD4 cell counts and higher viral loads. Resolution of these chronic changes was associated with decreasing CD4 cell counts but not with lower rates of clinical findings, viral load, or difference in survival. CONCLUSION: With increased survival, CRC are becoming more common. The resolution of these changes may indicate immunologic deterioration rather than clinical improvement. 相似文献
78.
Biomarkers for lysosomal storage disorders: identification and application as exemplified by chitotriosidase in Gaucher disease 总被引:1,自引:0,他引:1
Johannes M Aerts Marielle J van Breemen Anton P Bussink Karen Ghauharali Richard Sprenger Rolf G Boot Johanna E Groener Carla E Hollak Mario Maas Suzanne Smit Huub C Hoefsloot Age K Smilde Johannes PC Vissers Sheryas de Jong Dave Speijer Chris G de Koster 《Acta paediatrica (Oslo, Norway : 1992)》2008,97(S457):7-14
79.
Wang JF; Bashir M; Engelsberg BN; Witmer C; Rozmiarek H; Billings PC 《Carcinogenesis》1997,18(2):371-375
Chromium (Cr) is a human carcinogen and a potent DNA damaging agent.
Incubation of DNA with CrCl3 resulted in dose-dependent binding of Cr to
DNA and, at concentrations >20 microM, altered the electrophoretic
mobility of a 100 bp oligonucleotide. We also demonstrate that high
mobility group (HMG) proteins 1 and 2 bind Cr-damaged DNA (Cr-DNA). Protein
binding was lesion density-dependent, with maximal binding to DNA treated
with 100 microM CrCl3. HMG2 binds to Cr-DNA with a calculated Kd of
approximately 10(-9) M. These proteins also bound DNA obtained from
chromate-treated cells. These results suggest that the covalent attachment
of Cr to DNA induces alterations in DNA structure which are recognized by
HMG1 and HMG2. Therefore, these proteins may function as Cr-damaged DNA
recognition proteins in vivo and as a consequence of binding, may play a
role in directing the cellular response to Cr-DNA adduct formation.
相似文献
80.
NA Bridges JA Christopher PC Hindmarsh CG Brook 《Archives of disease in childhood》1994,70(2):116-118
The aetiology of 197 girls and 16 boys presenting with sexual precocity was reviewed. Ninety one girls and four boys had central precocious puberty (M:F 23:1); a cause was identified in all the boys but in only six girls. All boys with precocious puberty need detailed investigation; in girls investigation should be based on clinical findings, particularly the consonance of puberty. 相似文献