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31.
PINK1 mutations in sporadic early-onset Parkinson's disease. 总被引:5,自引:0,他引:5
Eng-King Tan Kenneth Yew Eva Chua K Puvan Hui Shen Esther Lee Kim-Yoong Puong Yi Zhao Ratnagopal Pavanni Meng-Cheong Wong Dominic Jamora Deidre de Silva Kyaw-Thu Moe Fung-Peng Woon Yih Yuen Louis Tan 《Movement disorders》2006,21(6):789-793
Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population. 相似文献
32.
A R Molina H Brasch S T Tan 《Journal of plastic, reconstructive & aesthetic surgery》2006,59(12):1458-1462
One serious complication of neurofibromatosis type 1 (NF1) is the development of malignant peripheral nerve sheath tumours (MPNSTs). These malignancies often develop within pre-existing plexiform neurofibromas and their development is now thought to be associated with both tumour suppressor gene mutations and dysregulated growth factor signalling. Recent work demonstrates that the lifetime risk of malignant transformation is significantly greater than previously thought. Ionising radiation, a long-standing disease, particularly the presence of a large number of plexiform neurofibromas from an early age, are suggested risk factors. We present an NF1 patient who developed an MPNST of the cervical vagus nerve which was successfully treated with surgery. Close monitoring of patients with NF and a high level of suspicion towards rapidly enlarging and painful swellings is merited as these features may signify malignant transformation. Whether a positive history of MPNST in other affected family members predisposes the individual to a higher risk of malignant transformation is unclear. 相似文献
33.
Jonathan Larkin Anne Bost John I Glass Seng-Lai Tan 《Journal of interferon & cytokine research》2006,26(12):854-865
Hepatitis C virus (HCV)-specific impairments in host immunity have been described at multiple levels of the innate and adaptive response, which may lead to viral persistence in the majority of infections. Understanding of HCV-associated immune defects could lead to novel therapeutic advances. Natural killer (NK) cells, the major effector cells of the innate immune system, are functionally impaired in chronic HCV infection. It has been suggested that this phenotype is a result of virus-specific defects in antigen-presenting cells (APCs) that regulate NK cell activity, as normal NK function is restored when they are stimulated ex vivo. In this study, we used human NK cell cytotoxicity assays to evaluate the activation-induced effects of NK cells on the HCV replicon-containing hepatic cells. We found that cytokine-activated NK cells were capable of inducing an HCV-associated, perforin/granzyme-dependent lysis of human hepatoma cells and that this required direct cellular contact and was independent of MHC class I expression levels. In contrast, on removal of cytokine stimulation, NK cells failed to exert any direct cytolytic effect on replicon targets. These findings suggest an important underlying mechanism by which NK cells control HCV infection and, with appropriate understanding of HCV-associated immune defects, could lead to novel therapeutic advances. 相似文献
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Clinical experience of phototherapy for non-haemolytic hyperbilirubinaemia in 3999 infants in Kandang Kerbau Hospital, Singapore, is documented. Phototherapy was most effective in extremely preterm infants with very low birth weight (gestation less than or equal to 32 weeks, birth weight less than or equal to 1500 g) and least effective in full term infants with very low birth weight (gestation greater than or equal to 37 weeks, birth weight less than or equal to 1500 g) and large preterm infants (gestation less than 37 weeks, birth weight greater than 2270 g). Overall, phototherapy was effective in almost all the infants, with a failure rate of only 2.00/1000 infants. No characteristic features common to all the failures could be detected. The bilirubin rebound was usually mild; repeat phototherapy was required in only 30 infants (7.50/1000), with the response to the second exposure comparable to that to the first. No infant required a third exposure. All the infants tolerated phototherapy well, none developing any illness that could be attributed to the treatment. This clinical experience shows that phototherapy for the treatment of nonhaemolytic hyperbilirubinaemia is effective and safe. 相似文献
38.
膳食黑米皮抑制高脂诱导的家兔动脉粥样硬化形成及其机制的初步探讨 总被引:1,自引:0,他引:1
目的 探讨膳食黑米皮对高脂诱导的家兔动脉粥样硬化形成的影响及其作用机制。方法 24只雄性新西兰大耳白家兔,按体重随机分为3组,分别饲以正常基础饲料、高脂饲料(含96%基础饲料、0.5%胆固醇、3.5%猪油)、黑米皮饲料(含 91%基础饲料、0.5%胆固醇、3.5%猪油、5%黑米皮),实验期为 60d。用图像分析法测定各组家兔主动脉脂质斑块面积,并分析家兔氧化与抗氧化状态。结果 黑米皮实验家兔的主动脉壁斑块面积较高脂组低66%(P<0.001);黑米皮组实验家兔的主动脉壁8-ohdG含量和血清及主动脉壁中MDA水平也低于高脂组(P<0.05 );而红细胞及主动脉壁中SOD水平和血清α-生育酚含量在两个处理组之间差异无显著性。结论 膳食黑米皮可以抑制高脂诱导的家兔动脉粥样硬化形成,其机制可能与之降低机体氧化应激水平及过氧化脂质生成有关。 相似文献
39.
Sherry X Yang Richard M Simon Antoinette R Tan Diana Nguyen Sandra M Swain 《Clinical cancer research》2005,11(17):6226-6232
PURPOSE: To delineate gene expression patterns and profile changes in metastatic tumor biopsies at baseline and 1 month after treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib in patients with metastatic breast cancer. EXPERIMENTAL DESIGN: Patients were treated with 150 mg of oral erlotinib daily. Gene expression profiles were measured with Affymetrix U133A GeneChip and immunohistochemistry was used to validate microarray findings. RESULTS: Estrogen receptor (ER) status by immunohistochemistry is nearly coincided with the two major expression clusters determined by expression of genes using unsupervised hierarchical clustering analysis. One of 10 patients had an EGFR-positive tumor detected by both microarray and immunohistochemistry. In this tumor, tissue inhibitor of metalloproteinases-3 and collagen type 1 alpha 2, which are the EGF-down-regulated growth repressors, were significantly increased by erlotinib. Gene changes in EGFR-negative tumors are those of G-protein-linked and cell surface receptor-linked signaling. Gene ontology comparison analysis pretreatment and posttreatment in EGFR-negative tumors revealed biological process categories that have more genes differentially expressed than expected by chance. Among 495 gene ontology categories, the significant differed gene ontology groups include G-protein-coupled receptor protein signaling (34 genes, P = 0.002) and cell surface receptor-linked signal transduction (74 genes, P = 0.007). CONCLUSIONS: ER status reflects the major difference in gene expression pattern in metastatic breast cancer. Erlotinib had effects on genes of EGFR signaling pathway in the EGFR-positive tumor and on gene ontology biological process categories or genes that have function in signal transduction in EGFR-negative tumors. 相似文献
40.
保留肾单位手术治疗早期小肾癌21例临床分析 总被引:1,自引:0,他引:1
Yao-Jun Xiao Shao-Bin Zheng Wan-Long Tan Tong Chen Huan Qi Zhi-Qiang Shao Yao-Dong Jiang Peng Wu Hui-Jian Zhang 《第一军医大学学报》2005,25(3):357-359
OBJECTIVE: To evaluate the clinical effects of nephron-sparing surgery in patients with early-stage small renal cell carcinoma. METHODS: Nephron-sparing surgery was performed in 21 patients with renal cell carcinoma including 1 with solitary kidney, 3 with unilateral tumor and contralateral renal compromise, and 17 with unilateral tumor and normal contralateral kidney. The diameter of the tumors ranged from 1.5 to 6.0 cm, with a mean of 2.8 cm. The tumor diameter in 17 patients with normal contralateral kidney was less than 4 cm (mean 2.5 cm) and the average diameter in 4 patients with contralateral renal compromise was 4.2 cm. Sixteen cases were in stage T(1), 4 in stage T(2), and 1 in stage T(3). Of the 21 patients, 4 underwent tumor enucleation, 10 polar nephrectomy and 7 wedge resection. RESULTS: All patients were followed up for an average of 40.8 months (7 to 66 months). One patient suffered a right lung and mediastinum metastasis 3 years after the surgery later and 1 with chronic glomerulonephritis required dialysis 27 months after the operation. No surgical complication or local recurrence were found in other patients. CONCLUSION: As a safe and effective therapy for early-stage small renal cell carcinoma, nephron-sparing surgery can be considered as the gold-standard therapy for patients with lesions less than 4 cm in T(1) and T(2) stages of localized unilateral tumor with normal contralateral kidney. 相似文献