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Biomedical subjects

Y R Wu

Publications and source records attributed to Y R Wu.

At least 19 recordsLinked to original sources
PubMed2006

alpha-Synuclein promoter RsaI T-to-C polymorphism and the risk of Parkinson's disease.

Increased alpha-synuclein expression may be involved in the pathogenesis of Parkinson's disease (PD). We investigated the association of Rep1 microsatellite and RsaI T-to-C substitution in the alpha-synuclein promoter region with the risk of PD by a case-control study. The RsaI C/C genotype and C allele were found less frequently in PD patients than in controls. A reduced risk of the Rep1-RsaI 0-C haplotype (OR = 0.57, 95% CI = 0.36-0.90) with PD was evident. The quantitative real-time PCR study showed that the alpha-synuclein mRNA expression was increased (although not significantly) in PD patients with RsaI T/T genotype or Rep1-RsaI 0-T haplotype as compared to T/C genotype or 0-C haplotype. Reporter constructs containing the RsaI C allele drove significantly lower transcriptional activity compared with the RsaI T allele in both IMR32 and 293 cells. The findings suggest that the RsaI T-to-C substitution may have a functional relevance to the susceptibility to PD.

Adult↗
PubMed2006

Apolipoprotein E, angiotensin-converting enzyme and kallikrein gene polymorphisms and the risk of Alzheimer's disease and vascular dementia.

Lipoproteins and vascular factors may play roles in the development of Alzheimer's disease (AD) and/or vascular dementia (VaD). In this study, odd ratios (ORs) and 95% confidence intervals (CIs) for apolipoprotein E (APOE), angiotensin-converting enzyme (ACE), and kallikrein (KLK1) polymorphisms were computed to test their association with the disease by a case-control study. The risk of AD was significantly increased for individuals with APOE varepsilon4 allele (OR = 3.73, 95% CI = 2.38-5.98). The risk of AD was also significant for people with ACE DD genotype, D allele, or T-D haplotype [OR (95% CI) = 4.29 (1.96-10.23), 1.90 (1.35-2.70), or 2.91 (1.71-5.10), respectively]. The above association between ACE-VaD was also strong (p = 0.0012, 0.0050, 0.0007, respectively). Reporter constructs containing the -240 A or T allele displayed similar transcriptional activity in both HEK-293 and IMR-32 cells. Thus, another putative pathogenic marker that is linked with the Alu D allele might affect the risk of AD and VaD in Taiwan.

Alzheimer Disease↗
PubMed2006

Association of tau haplotype-tagging polymorphisms with Parkinson's disease in diverse ethnic Parkinson's disease cohorts.

BACKGROUND: The overlap in the clinical and pathological features of tauopathies and synucleinopathies raises the possibility that the tau protein may be important in Parkinson's disease (PD) pathogenesis. Several MAPT polymorphisms that define the tau H1 haplotype have been investigated for an association with PD with conflicting results; however, two meta-analyses support an association between haplotype H1 and PD. METHODS: In this study, we recruited 508 patients and 611 healthy controls from Greek, Finnish and Taiwanese populations. We examined the possible genetic role of variation within MAPT in PD using haplotype-tagging single polymorphisms (SNPs) in these ethnically different PD populations. RESULTS: We identified a moderate association at SNP rs3785883 in the Greek cohort for both allele and genotype frequency (p = 0.01, p = 0.05, respectively) as well as for SNP rs7521 (genotype p = 0.02) and rs242557 (p = 0.01 genotypic, p = 0.04 allelic) in the Finnish population. There were no significant differences in genotype or allele distribution between cases and controls in the Taiwanese cohort. CONCLUSION: We failed to demonstrate a consistent association between the MAPT H1 haplotype (delineated by intron 9 ins/del) and PD in three ethnically diverse populations. However, the data presented here suggest that subhaplotypes of haplotype H1 may confer susceptibility to PD, and that either allelic heterogeneity or different haplotype composition explain the divergent haplotype results.

Adult↗
PubMed2006

Clinical characteristics of multiple sclerosis in Taiwan: a cross-sectional study.

This study reviewed the clinical characteristics of multiple sclerosis (MS) in Taiwanese patients from 1993 to 2001. Of the 75 MS patients with a mean age of onset of 35.6 +/- 12.6 years, the female-to-male ratio was 4.4 (61/14). In 42 (56%) optico-spinal MS (OS-MS) patients, the age of onset (37.6 +/- 11.1 years) tended to be older than conventional MS (C-MS) patients (33.1 +/- 14.1 years, P = 0.08). In 60 cerebrospinal fluid (CSF) specimens, raised IgG index (>0.7) and oligoclonal bands were noted in 26 (43.3%) and two (3.3%) cases, respectively. The frequency of raised IgG index was lower in OS-MS (31.3%) than in C-MS (57.1%, P = 0.07). The CSF total protein concentrations were significantly higher in OS-MS (64.5 mg/dL) than in C-MS (46.6 mg/dL, P = 0.047). The mean annual relapse rate was 54.1%, and was significantly higher within the first year (59.7%, P < 0.001). The mean annual relapse rate in OS-MS (62.7%) was significantly higher than in C-MS (41.2%, P=0.01). The differences in the annual relapse rate and total protein concentration in CSF between OS-MS and C-MS suggest probably two distinct immunopathogenesis. The higher first year relapse rate of MS patients in Taiwan may address the importance of early intervention with immunomodulatory therapy.

Adult↗
PubMed2005

Heat shock protein 70 and tumor necrosis factor alpha in Taiwanese patients with dementia.

This study was to determine whether polymorphisms of heat shock protein 70-1 (HSP70-1) and tumor necrosis factor alpha (TNF-alpha) are associated with the risk of Alzheimer's disease (AD) and vascular dementia (VaD). Using the criteria of the NINCDS-ADRDA and NINDS-AIREN, 125 AD patients, 57 VaD patients and 109 ethnically matched nondemented controls were enrolled. The HSP70-1 -110 A/C and TNF-alpha -1031 T/C, -863 C/A and -857 C/T polymorphisms were analyzed by means of genotype or haplotype association methods. None of the four genotypes examined showed a statistically significant difference in genotype distribution between the AD cases and controls. However, the HSP70-1 -110 CC genotype occurred more frequently among AD cases (p=0.0821; odds ratio: 2.08; 95% confidence interval, CI: 0.92-4.98). The overall genotype distribution among the VaD cases tended to be different at the HSP70-1 -110 and TNF-alpha -1031 sites (p=0.0604 and 0.0316, respectively). The HSP70-1 -110 CC genotype was more frequent (p=0.0459), and the association of the -110 CC genotype with VaD was evident (p=0.0207; odds ratio: 3.22; 95% CI: 1.20-8.87). The more frequent TNF-alpha -1031 TC genotype (p=0.0614) was also evidently associated with VaD (p=0.0209; odds ratio: 2.32; 95% CI: 1.14-4.78). Multivariate analysis demonstrated the synergistic effect of the HSP70-1 -110 CC and TNF-alpha -1031 TC/CC genotypes on VaD (p=0.0091; odds ratio: 10.09; 95% CI: 2.01-75.97). Haplotype analysis among TNF-alpha -1031, -863, -857 sites revealed that -1031C-857C may act as a risk haplotype among VaD cases (p=0.0132, odds ratio: 2.26; 95% CI: 1.19-4.33). Our results suggest a potential protective role for HSP70 in both VaD and AD, whereas TNF-alpha may act as a risk factor only for VaD, and not for AD.

Aged↗
PubMed2004

Analysis of polyglutamine-coding repeats in the TATA-binding protein in different neurodegenerative diseases.

Trinucleotide repeat (TNR) expansion in the gene for TATA binding protein (TBP) has recently been described as causal for spinocerebellar ataxia type 17. The normal number of repeats has been considered to be 42 or less. An intermediate range with reduced penetrance has been assumed to be 43-47 CAA/CAG repeats. We examined this gene in 30 patients with autosomal-dominant cerebellar ataxia (ADCA), 35 patients with sporadic ataxia, 11 patients with Huntington's disease (HD), 351 patients with idiopathic Parkinson's disease (PD), 105 patients with Alzheimer's disease (AD), and 291 controls with no history of neurodegenerative disease. Three patients (one with sporadic PD and two with AD) carrying more than 42 TNRs in the TBP gene were identified. This reveals that the phenotype associated with CAG/CAA expansion in the TBP gene may be heterogeneous.

Aged↗
PubMed2004

DNA haplotype analysis of CAG repeat in Taiwanese Huntington's disease patients.

We studied the expanded CAG repeat and adjacent CCG repeat in 53 Huntington's disease (HD) patients and 172 unrelated normal subjects matched to the patients for ethnic origin. The range of the CAG repeat varied from 38 to 109 in the HD patients and from 10 to 29 in the control group. A significant negative correlation was found between the age at onset and the CAG expansion, with no significant influence of the adjacent CCG repeat on the age at onset by multiple regression analysis. Allelic association using CCG repeat and 2 flanking dinucleotide repeat markers within 150 kb of the HD gene revealed linkage disequilibrium for 2 of 3 markers. Haplotype analysis of 24 HD families using these markers identified 3 major haplotypes underlying 87.5% of HD chromosomes. The data suggested frequent haplotypes in the Taiwanese population on which one or more mutational events leading to the disease occurred.

Alleles↗
PubMed2004

Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson's disease.

DNA tests in normal subjects and patients with ataxia and Parkinson's disease (PD) were carried out to assess the frequency of spinocerebellar ataxia (SCA) and to document the distribution of SCA mutations underlying ethnic Chinese in Taiwan. MJD/SCA3 (46%) was the most common autosomal dominant SCA in the Taiwanese cohort, followed by SCA6 (18%) and SCA1 (3%). No expansions of SCA types 2, 10, 12, or dentatorubropallidoluysian atrophy (DRPLA) were detected. The clinical phenotypes of these affected SCA patients were very heterogeneous. All of them showed clinical symptoms of cerebellar ataxia, with or without other associated features. The frequencies of large normal alleles are closely associated with the prevalence of SCA1, SCA2, MJD/SCA3, SCA6, and DRPLA among Taiwanese, Japanese, and Caucasians. Interestingly, abnormal expansions of SCA8 and SCA17 genes were detected in patients with PD. The clinical presentation for these patients is typical of idiopathic PD with the following characteristics: late onset of disease, resting tremor in the limbs, rigidity, bradykinesia, and a good response to levodopa. This study appears to be the first report describing the PD phenotype in association with an expanded allele in the TATA-binding protein gene and suggests that SCA8 may also be a cause of typical PD.

Age of Onset↗
PubMed2004

The use of evoked potentials for clinical correlation and surgical outcome in cervical spondylotic myelopathy with intramedullary high signal intensity on MRI.

OBJECTIVE: To investigate the use of motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) for clinical significance and surgical outcome in patients with cervical spondylotic myelopathy (CSM) with intramedullary high signal intensity on T2 weighted MRI. METHODS: Forty nine patients were scored according to the modified Japanese Orthopaedic Association (JOA) score for cervical myelopathy. MEP and SEP studies were performed and the results were categorised as normal or abnormal. Thirty nine patients who had received surgical decompression were re-evaluated after 6 months. Surgical outcome was represented by the recovery ratio of the JOA score. RESULTS: Abnormal MEPs were observed in 44 patients (arm: 43; leg: 30). Abnormal SEPs were found in 32 patients: (median: 24; tibial: 23). Patients with abnormal SEPs had a worse JOA score than those with normal SEPs. Thirty nine patients received surgical treatment. Patients younger than 55 had better recovery ratios than those who were 55 or older (p = 0.005, two sample Student's t test). Patients with normal median SEPs also had better recovery ratios than those with abnormal median SEPs (p = 0.007, two sample Student's t test). Among median SEP variables, only N9-20 was significantly associated with recovery ratio (p = 0.016, stepwise linear regression), with age factor controlled (p = 0.025, stepwise linear regression). CONCLUSION: Arm MEP was the most sensitive EP test for detecting myelopathy in patients with chronic CSM. Median and tibial SEPs correlated well with the severity of myelopathy while normal median SEPs correlated with good surgical outcome. Among median SEP variables, only N9-20 correlated with surgical outcome.

Adult↗
PubMed2003

Mapping QTLs and candidate genes for rice root traits under different water-supply conditions and comparative analysis across three populations.

To investigate the genetic factors underlying constitutive and adaptive morphological traits of roots under different water-supply conditions, a recombinant inbred line (RIL) population derived from a cross between the lowland rice variety IR1552 and the upland rice variety Azucena with 249 molecular markers, was used in cylindrical-pot experiments. Eighteen QTLs were detected for seminal root length (SRL), adventitious root number (ARN), and lateral root length (LRL) and lateral root number (LRN) on the seminal root at a soil depth of from 3 to 6 cm under flooding and upland conditions. One identical QTL was detected under both flooding and upland conditions. The relative parameters under the two water-supply conditions were also used for QTL analysis. Five QTLs for upland induced variations in the traits were detected with the positive alleles from Azucena. A comparative analysis was performed for the QTLs detected in this study and those reported from two other populations with Azucena as a parent. Several identical QTLs for root elongation were found across the three populations with positive alleles from Azucena. Candidate genes were screened from ESTs and cDNA-AFLP clones for comparative mapping with the detected QTLs. Two genes for cell expansion, OsEXP2 and endo-1,4-beta-D-glucanase EGase, and four cDNA-AFLP clones from root tissues of Azucena, were mapped on the intervals carrying the QTLs for SRL and LRL under upland conditions, respectively.

Blotting, Northern↗
PubMed2001

Orthostatic tremor arises from an oscillator in the posterior fossa.

We tested the hypotheses that orthostatic tremor is generated by a central oscillator and that the tremor is expressed through spinal Ib interneurons. Six patients with orthostatic tremor were examined. The tremor was reset by electrical stimulation over the posterior fossa at intensities that were below the threshold for a motor evoked potential (MEP) but was not reset by transcranial magnetic stimulation over the motor cortex that did produce an MEP. It is argued that the oscillator involves the cerebellum or brainstem. The inhibition of voluntary EMG produced by stimulation over tendons, which has been attributed to effects from Golgi tendon organs (GTO), was not modulated in synchrony with the tremor. We were unable to demonstrate, therefore, that the tremor is expressed through GTO interneurons with this method.

Aged↗
PubMed2001

Does stimulation of the GPi control dyskinesia by activating inhibitory axons?

A 69-year-old woman with Parkinson's disease and levodopa-induced dyskinesias had a deep brain stimulation (DBS) electrode inserted into the right globus pallidus internus (GPi). During the operation, the GPi was mapped with dual microelectrode recordings. Stimulation through one microelectrode in GPi inhibited the firing of GPi neurons recorded with another microelectrode 600--1,000 microm distant. The inhibition could be obtained with pulse widths of 150 micros and intensities as low as 10 microA. Single stimuli inhibited GPi neurons for approximately 50 ms. Trains of 300 Hz stimuli inhibited GPi neuron firing almost completely. Postoperatively, stimulation through macroelectrode contacts located in the posterior ventral pallidum controlled the patient's dyskinesias. The effect could be obtained with pulse widths of 50 micros and frequencies as low as 70--80 Hz. We postulate stimulation of the ventral pallidum controls dyskinesias by activating large axons which inhibit GPi neurons.

Action Potentials↗
PubMed1998

Haemophilus influenzae meningitis in adults.

Haemophilus influenzae meningitis is rare in adults. We reviewed the microbiological records of cerebrospinal fluid (CSF) and blood cultures and the medical records of patients with bacterial meningitis admitted to Chang Gung Memorial Hospital from January 1978 to May 1996. Haemophilus influenzae meningitis was found in six adult patients, accounting for 1.8% of 326 bacteriologically proven adult cases of meningitis diagnosed between January 1984 and May 1996. Predisposing conditions included head trauma and/or neurosurgical procedure in four patients and an extracranial extension of a pituitary adenoma in a diabetic patient. None of them had altered consciousness on the day of treatment. A CSF cell count less than 500 x 10(6) leukocytes/liter was noted in three patients. Antibiotic therapy was successful in all patients. Thus, predisposing conditions, particularly head trauma and/or neurosurgical procedure, are commonly present in adult patients with H. influenzae meningitis. Patients with the infection may have a low cellular count in the CSF that may be readily misinterpreted as meningitis caused by other pathogens.

Adult↗
PubMed1996

Case report: Pontine haemorrhage following iohexol lumbar myelography.

A case of pontine haemorrhage following lumbar myelography using iohexol is described. Stress, inducing transient hypertension during the procedure, with superimposed neurotoxicity from contrast medium (iohexol) is suggested as a possible mechanism. No brain stem lesion was seen on the initial brain CT scan, possibly because of the high attenuation of the contrast medium in the subarachnoid space. A delayed CT brain scan demonstrated the pontine haemorrhage and was necessary to confirm the diagnosis.

Cerebral Hemorrhage↗
PubMed1996

Vocal cord paralysis as an initial sign of multiple system atrophy in the central nervous system.

Multiple system atrophy (MSA) of the central nervous system has been recognized as a rare cause of stridor secondary to vocal cord paralysis. This respiratory problem usually occurs in the later stages of the disease. We report the case of a 53-year-old man who presented with bilateral vocal cord paralysis accompanied by stridor and sleep apnea, which were relieved by a tracheostomy. Two years after the onset of stridor, he developed extrapyramidal and cerebellar signs combined with severe autonomic failure. Magnetic resonance imaging of the brain revealed atrophy of the brainstem and cerebellum. This clinical picture is consistent with the diagnosis of MSA. Vocal cord paralysis preceding any other neurologic and autonomic manifestations has been infrequently described. This case should remind clinicians that MSA should be considered in the differential diagnosis of vocal cord palsy of undetermined origin.

Atrophy↗
PubMed1995

Rimmed, vacuolar distal myopathy in two Taiwanese siblings.

Distal myopathy with rimmed vacuoles (DMRV) is a rare disease that has not previously been reported in Taiwan. This paper reports two siblings with DMRV. Each showed a different pattern of disease progression, one being slowly and the other rapidly progressive. Both patients' initial symptoms appeared in early adulthood, manifesting as muscular wasting and weakness of the legs, especially in the distal muscles. Severe generalized involvement of skeletal muscles, with sparing of the facial, extraocular, bulbar, intercostal and diaphragm muscles was recognized in the advanced stage. The striking finding in their muscle biopsy specimens was the presence of "rimmed" vacuoles. Magnetic resonance imaging showed more severe involvement of the anterior compartment muscles of the lower legs. DMRV is thought to be inherited as an autosomal recessive trait and is distinguishable from other types of distal myopathy on the basis of clinical and pathologic findings. The literature on the subject is reviewed with emphasis on the differences between distal myopathic syndromes.

Adult↗
PubMed1990

Unique role of oxygen in regulation of hepatic monooxygenation and glucuronidation.

The purpose of this study was to evaluate the hypothesis that NADPH supply in intact cells is regulated by oxygen tension. This was accomplished by studying monooxygenation in perfused livers from Ah locus-responsive C57BL/6J mice, where rates of monooxygenation are high. Elevation of flow rate decreases the hepatic O2 gradient and increases O2 delivery to the organ. Under these conditions, rates of p-nitroanisole O-demethylation were 2-3 times higher in perfused livers from fed or fasted mice at high (10 ml/min) compared with normal (5 ml/min) flow rates. Rates of monooxygenation were directly proportional to oxygen tension (half-maximal rates occurred with approximately 400 microM O2). On the other hand, rates were independent of oxygen concentration in isolated microsomes where NADPH was supplied in excess. The decrease in rate due to diminished O2 concentration in the intact organ could not be attributed to hypoxia, because O2 tension in the effluent perfusate exceeded 50 microM even when influent perfusate was saturated with 25% O2 and ATP/ADP ratios were in the normal range. Thus, monooxygenation of p-nitroanisole in perfused mouse liver is dependent on oxygen tension. Similarly, glucuronidation of p-nitrophenol was oxygen dependent in the intact organ but not in isolated microsomes supplemented with UDP-glucuronic acid. Taken together, these data support the hypothesis that, at high oxygen tensions (e.g., in periportal regions of the liver lobule), mitochondrial activity is increased, which in turn enhances NADPH and UDP-glucuronic acid turnover, leading to accelerated rates of monooxygenation and glucuronidation in intact cells. In support of this idea, NH4Cl, which utilizes NADPH for urea synthesis, inhibited monooxygenation in the perfused mouse liver at high but not low flow rates. Thus, important phase I and II detoxification reactions are regulated indirectly by the hepatic oxygen gradient, via mechanisms involving cofactor supply, when cytochrome P-450 is not limiting.

Animals↗