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Biomedical subjects

Y Yuen

Publications and source records attributed to Y Yuen.

9 recordsLinked to original sources
PubMed2006

Exploring the relationship between caffeine intake and essential tremor.

BACKGROUND: It has been suggested that environmental factors may be associated with essential tremor (ET). This study was carried out to evaluate the association of caffeine intake with ET. METHOD: In a case control study, patients diagnosed with ET and healthy controls underwent a standardized questionnaire interview to evaluate the exposure to coffee and tea intake. A multivariate logistic regression analysis was carried out to evaluate the association of caffeine intake and other environmental factors with risk of ET. RESULTS: 179 subjects including 79 ET patients and 100 controls matched for age, gender and ethnicity were included in the analysis. Univariate analysis revealed that caffeine consumption in ET patients was higher than control group (median and 90th percentile range: 2300 (0, 9000) mg-years versus 1500 (0, 6090) mg-years, p=0.01). However, the multivariate logistic regression analysis demonstrated that caffeine was no longer a significant factor associated with ET (p=0.119). There was no significant correlation between amount of caffeine intake and disease duration (Spearman's r=0.194; p=0.202) or total tremor score (Spearman's r=0.045; p=0.771) in ET patients. CONCLUSION: Caffeine consumption was not associated with risk of ET in our study population. Further studies are needed to investigate the significance of gene-environmental interaction in ET.

Adult↗
PubMed2006

The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence.

Evidence of LRRK2 haplotypes associated with Parkinson's disease (PD) risk was recently found in the Chinese population from Singapore, and a common LRRK2 missense variant, Gly2385Arg, was independently detected as a putative risk factor for PD in the Chinese population from Taiwan. To test the association between the Gly2385Arg variant in a large case-control sample of Chinese ethnicity from Singapore, and to perform functional studies of the wild type and Gly2385Arg LRRK2 protein in human cell lines. In a case-control study involving 989 Chinese subjects, the frequency of the heterozygous Gly2385Arg genotype was higher in PD compared to controls (7.3 vs. 3.6%, odds ratio = 2.1, 95% CI: 1.1-3.9, P = 0.014); these values yield an estimated population attributable risk (PAR) of approximately 4%. In a multivariate logistic regression analysis with the disease group (PD vs. controls) as the dependent variable and the genotype as an independent factor with adjustments made for the effect of age and gender, the heterozygous Gly2385Arg genotype remained associated with an increased risk of PD compared to wild type genotype (odds ratio = 2.67, 95% CI: 1.43-4.99, P = 0.002). The glycine at position 2385 is a candidate site for N-myristoylation, and the Gly2385Arg variant replaces the hydrophobic glycine with the hydrophilic arginine, and increases the net positive charge of the LRRK2 WD40 domain. In transfection studies, we demonstrated that both the wild type and Gly2385Arg variant LRRK2 protein localize to the cytoplasm and form aggregates. However, under condition of oxidative stress, the Gly2385Arg variant was more toxic and associated with a higher rate of apoptosis. Our study lends support to the contention that the Gly2385Arg is a common risk factor for PD in the Chinese population. Our bioinformatics and in-vitro studies also suggest that the Gly2385Arg variant is biologically relevant and it might act through pro-apoptotic mechanisms.

Aged↗
PubMed2006

Genetic analysis of SCA2, 3 and 17 in idiopathic Parkinson's disease.

Recent reports of SCA2 and SCA3 patients who presented with levodopa responsive parkinsonism have generated considerable interest as they have implications for genetic testing. It is unclear whether ethnic race alone or founder effects within certain geographical region explain such an association. In this study, we conducted genetic analysis of SCA2, 3, 17 in an ethnic Chinese cohort with early onset and familial Parkinson's disease (PD) and healthy controls. A total of 191 subjects comprising of 91 PD and 100 healthy controls were examined. We identified one positive case of SCA2 in an early-onset sporadic PD patient who had CAG 36 repeats, yielding a prevalence of 2.2% in early-onset sporadic PD patients and less than 1.0% in our study PD population. The size of the repeats was lower than the expanded repeats (38-57) in SCA2 patients with ataxia in our population. All the children of the patient were physically normal even though some of them carried the repeat expansion of similar size. No cases and controls were positive for SCA3 and SCA17. We do not think routine screening of SCA2, SCA3 and SCA17 for all idiopathic PD patients is cost-effective in our ethnic Chinese population. However, SCA2 should be a differential diagnosis in young onset sporadic PD when genetic mutations of other known PD genes have been excluded.

Adult↗
PubMed2005

Analysis of LRRK2 functional domains in nondominant Parkinson disease.

A comprehensive sequence analysis of 29 exons that code for the functional domains of LRRK2 in 160 nondominant Parkinson disease (PD) patients was performed. Novel variant screening in a further 470 sporadic PD patients and 630 controls revealed two novel variants (R1067Q and IVS33 + 6 T>A), which are likely to be pathogenic in five patients. One patient presented initially with a typical essential tremor phenotype, expanding the phenotypic spectrum of LRRK2 mutations.

Adult↗
PubMed2005

Impaired transcriptional upregulation of Parkin promoter variant under oxidative stress and proteasomal inhibition: clinical association.

We provided data to show that the transcriptional activity of wildtype -258T in the parkin promoter region was significantly higher than the -258G variant in human cell lines. The transcriptional activity of wildtype -258T was significantly increased under oxidative stress by hydrogen peroxide, but this was not observed for the -258G variant. The transcriptional upregulation was significantly higher for wildtype -258T compared to -258G variant at 0.1, 0.2 and 0.4 mM of hydrogen peroxide. Similar results were obtained when the cells were treated with a proteasome inhibitor, MG132.Furthermore, in a case control study involving 753 subjects, we demonstrated that the parkin promoter -258G variant was associated with an increased risk of sporadic Parkinson's disease (PD) in the elderly ethnic Chinese population. Our clinical and laboratory data provide corroborative evidence that some older individuals who have the -258G variant may have a higher risk of developing PD.

Age Factors↗
PubMed2005

Differential expression of splice variant and wild-type parkin in sporadic Parkinson's disease.

BACKGROUND: Altered splicing of parkin under cellular stress could lead to changes in gene expression and altered protein activity. The causative role of parkin in sporadic Parkinson's disease (PD) is unknown. OBJECTIVES: We described a parkin splice variant (SV) in the substantia nigra and leukocytes of sporadic PD patients. Using a case control methodology, we investigated the exon 4 SV (E4SV) and wild-type parkin expression in the leukocytes of sporadic PD patients and healthy individuals. METHODS/RESULTS: We identified a parkin E4SV in the substantia nigra and leukocytes of sporadic PD patients and controls by reverse transcriptase-polymerase chain reaction (PCR). The exon 4 (122 bp) deletion resulted in a reading frame shift over the junction of exons 3-5 and a stop codon (tga) 17 bp downstream from exon 3. The translated truncated protein was associated with a total loss of the two-RING finger functional domain. Utilizing TaqMan real-time PCR with probes located across the junction of exons 3-4 or 3-5, we demonstrated an over-expression of E4SV/wild-type parkin ratio in the leukocytes of sporadic PD patients compared to age-, gender-, and race-matched controls (p<0.0005). A multivariate regression analysis demonstrated that the ratio of E4SV/wild-type parkin expression increased with age in PD patients, but this was not observed in the controls (p<0.0005). CONCLUSION: The relative expression of E4SV/wild type parkin was increased in sporadic PD compared to healthy controls. Based on our observations, further functional studies to determine the pathophysiologic role of E4SV in sporadic PD patients will be of importance.

Aged↗
PubMed1992

Cardiac life support training: the Ministry of Health's experience.

This study reviews the records of all cardiac life support training courses conducted at the Ministry of Health's Life Support Training Centre situated in Singapore General Hospital over a six period from 1985 to 1990. A total of 1,789 persons were trained in Basic Life Support (BCLS), 65 as BCLS Instructors, 267 in Advanced Cardiac Life Support (ACLS), 276 in Emergency Cardiac Care (ECC) and 24 in Emergency Cardiac Defibrillation (ECD). These courses have involved a total of 1111 doctors, 1248 nurses and 62 ancillary staff. At the end of the course, 90.7% of those learning BCLS agreed that they would use their CPR skills, if required. Only 60% felt they would use mouth-to-mouth ventilation. Of 415 who expressed an interest in becoming instructors, 15.7% have, to-date, been trained. While more than 80% of persons learning, ACLS were doctors, only 25% of these were willing to instruct. There are currently 14 ACLS instructors. The ECC courses were modified from the ACLS course and taught to Emergency Room doctors only. It was found to be immensely popular with 98% expressing benefit. The ECD programme trained emergency ambulance nurses in the use of semi-automatic electrical defibrillators. The marked increased in yearning for cardiac life support skills amongst medical and nursing staff has been a major factor in the proliferation of life support training programmes at the Centre. Nurturing this enthusiasm is the key to ensuring that the programmes continue to expand for the benefit of both inpatients and the out-of-hospital lay public.

Attitude of Health Personnel↗
PubMed1989

A pilot study on intensive lipid lowering--a new approach to cardiac rehabilitation.

The deleterious effects of raised plasma lipids on the progression of coronary artery disease has been well established. Recent research data suggests that intensive lipid lowering represents a new approach to Cardiac Rehabilitation. There was a total of twenty-four participants with twenty-one (87.5%) males and three (12.5%) females. There were seventeen Chinese (70.8%), six Indians (25%) and one Malay (4.2%). Their ages ranged from group forty to forty-nine, five participants (20%); fifty to fifty-nine, twelve participants (50%); sixty to sixty-nine, six participants (25%) and seventy to seventy-nine, one participant (5%). In this study, twelve individuals were treated with Cholestyramine, seven by Gemfibrozil, four by Clofibrate and three by Bezafibrate. The duration of antilipid treatment ranged from two to eighteen months (mean eight months). Side effects were reported in twelve patients (50%) on Cholestyramine who complained of constipation while one (4%) on Bezafibrate had abnormal liver function tests (raised SGOT and SGPT). All patients had been on an exercise and diet control program for one year which they were enrolled in an intensive lipid-lowering protocol. The pre and post treatment lipid profiles with lipid-lowering agents showed 18% reduction for Triglycerides, 15% reduction for Total Cholesterol, 5% increase for HDL-Cholesterol, 19% decrease in LDL Cholesterol, 19% decrease in Total Cholesterol: HDL ratios. The initial results suggest that an intensive lipid-lowering strategy in a Cardiac Rehabilitation Program appears to have a beneficial effect on lipid profiles and represents an expanded approach to lipid management involving exercise, nutrition and pharmacological intervention.

Adult↗