Biomedical subjects

Yah-Huei Wu Chou

Publications and source records attributed to Yah-Huei Wu Chou.

10 recordsLinked to original sources

PubMed2005

DYT1 mutation in a cohort of Taiwanese primary dystonias.

To investigate the DYT1 gene mutation in Chinese ethnic, we examined a series of 200 patients with primary dystonias (11 familial and 189 sporadic), 53 of their asymptomatic relatives, 97 patients with familial or early-onset parkinsonism, and 200 healthy subjects. The GAG deletion at codon 946 was only found in three sporadic dystonia patients and seven of their asymptomatic familial members. The frequency of GAG deletion was 1.5% in dystonia patients, and was 6.7% in early-onset dystonias (< or = 26 years). We conclude that DYT1 mutation is a minor cause of primary dystonias in a cohort of Taiwanese population.

Adolescent↗

PubMed2005

Autonomic dysfunction in Machado-Joseph disease.

OBJECTIVE: Machado-Joseph disease is an autosomal dominant spinocerebellar ataxia with expanded trinucleotide repeats. Although autonomic nervous system degeneration was documented in postmortem reports, the autonomic dysfunction in patients with Machado-Joseph disease, either in clinical analysis or electrophysiological investigations, has not yet been studied in detail. METHODS: Fifteen patients with genetically confirmed Machado-Joseph disease and 34 healthy subjects were studied. The study design included a detailed questionnaire, R-R interval variation on deep breathing or Valsalva maneuver, and sympathetic skin response evoked by electrical stimulation of the median nerve or magnetic stimulation of the neck. RESULTS: Sixty-seven percent of patients had at least 3 symptoms involving different aspects of autonomic functions. Voiding problems and thermoregulatory disturbance were the most common symptoms. Ten (71%) of 14 patients had abnormal R-R interval variation with a significant reduction of the mean ratio. Prolonged latency or absence of sympathetic skin response to electrical stimulation was identified in 73% of patients and to magnetic stimulation, in 53%. R-R interval variation and sympathetic skin response showed good correlation with the functional stage. Electrical stimulation revealed the highest sensitivity, specificity, and positive predictive value compared with other tests. CONCLUSION: The present investigation documents that autonomic dysfunction is not uncommon in patients with Machado-Joseph disease and might be related to the clinical progression.

Adult↗

PubMed2005

Taiwanese cases of SCA2 are derived from a single founder.

We have assessed the haplotypes at the ATXN2 locus in Taiwanese controls and in individuals with SCA2 ataxia with both ataxic and parkinsonian features. Our intention was to determine whether a different ataxin 2 haplotypes predisposed to the two phenotypes. In fact, our analysis showed that all SCA2 mutations carriers had the same ataxin 2 haplotype: haplotype B, which accounts for only 15% of control haplotypes, implying that there is a common founder for all Taiwanese SCA2 patients.

Adult↗

PubMed2005

Mutations of the PKD2 gene in Taiwanese patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Mutation analysis in the context of clinical phenotypes helps clarify the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). Over 78 PKD2 gene mutations have been reported in the literature, but few have been described from an Asian population. This study attempted to characterize PKD2 mutations and their clinical implications among Taiwanese. METHODS: Twenty unrelated ADPKD patients with uncharacterized genotypes were screened for mutations in the PKD2 gene via single-strand conformation polymorphism (SSCP) of PCR products from genomic DNA, using previously reported PCR conditions and primers. RESULTS: This study identified two novel mutations (C681A and 2136-2137delG) and one mutation (C2407T) previously reported in a Cypriot family. Overall, we found PKD2 mutations in 15% (three out of 20) of the ADPKD patients screened. The mutations included two nonsense mutations (Y227X and R803X) and one frameshift mutation (712-715X) that could all lead to premature termination of translation. The locations of mutations in this study spanned the entire PKD2 gene on exons 2, 11, and 13 without clustering and did not influence the renal disease severity. CONCLUSIONS: The study identified two novel mutations and one recurrent mutation of the PKD2 gene in 20 Taiwanese patients. The characteristics of the mutations in this study resemble those reported among Western populations.

Adult↗

PubMed2004

Influence of age on adenomatous polyposis coli and p53 mutation frequency in sporadic colorectal cancer-rarity of co-occurrence of mutations in APC, K-ras, and p53 genes.

INTRODUCTION: Previous studies have investigated the possibility that specific mutations may be related to specific clinicopathological features. However, most previous investigations included only an average age (40-80 years) group of sporadic colorectal cancers and, moreover, studied only a single gene in isolation. Therefore, the influence of age on these mutation frequencies remains unclear, despite age being considered a risk factor for genetic mutation. MATERIALS AND METHODS: This study included 122 sporadic colorectal cancers from three different age groups and analyzed mutation frequencies of adenomatous polyposis coli (APC), K-ras, and p53 genes and microsatellite instability to determine their mutation frequencies and relationships with clinicopathological features. RESULTS: Significantly lower p53 mutation frequencies were observed among young (32 years old or younger) and old (86 years old or older) patient groups compared with an average age (39-85 years old) patient group (14.3% and 19.2% versus 51.5%, P<0.001). APC mutation frequency (11.8%) was significantly lower in highly aggressive (Dukes' stage D) tumors ( P=0.003) than in the other stage tumors (Dukes' stage A, B, and C). Additionally, simultaneous occurrence of all three genetic alterations in an individual tumor was rare (below 5%). Statistical analysis further confirmed that mutation number in Dukes' D tumors occurred less frequently than expected in other stage tumors ( P=0.008). CONCLUSIONS: Genetic alterations of sporadic colorectal cancers have different relationships with age or tumor stage. Additionally, most sporadic colorectal tumors do not necessarily require following the widely accepted genetic model, because the three key genetic mutations, APC, K-ras, and p53, rarely occur simultaneously.

Adenomatous Polyposis Coli↗

PubMed2004

The parkinsonian phenotype of spinocerebellar ataxia type 2.

BACKGROUND: We recently reported that spinocerebellar ataxia type 2 (SCA2) caused familial parkinsonism in 2 brothers with predominant symptoms of resting tremor, rigidity, and bradykinesia that responded to levodopa. OBJECTIVE: To investigate SCA2 as the possible cause of familial parkinsonism in our series and subsequently to analyze the correlation between the clinical manifestation and CAG repeat size in the ataxin-2 gene product. PATIENTS: One hundred thirty patients from 41 families with familial parkinsonism were examined for SCA2. Another 8 patients with the classic ataxic phenotype of SCA2 from 6 families were the control group. DESIGN: The length of expanded CAG repeat was analyzed by means of polymerase chain reaction. The clinical data and genetic findings in the parkinsonian phenotype were then compared with those in the ataxic phenotype. RESULTS: We found expanded CAG repeats in the ataxin-2 gene product in 7 patients from 4 families with parkin-sonism, which was about 10% of our familial parkinsonism series. The parkinsonian phenotype was characterized by resting tremor, rigidity, and bradykinesia. Only mild dysarthria, ataxic gait, and instability were noted, particularly in the late stage. Patients with the parkinsonian phenotype had an older mean +/- SD age of symptom onset (45.8 +/- 13.9 years) and shorter mean +/- SD abnormal CAG length (36.2 +/- 1.1 repeats) than did those with the ataxic phenotype (26.9 +/- 11.0 years and 43.1 +/- 3.2 repeats). Parkinsonian SCA2 responded well to levodopa. CONCLUSIONS: We conclude that SCA2 is a minor cause of familial parkinsonism, particularly in Taiwan. The parkinsonian phenotype is associated predominantly with a shorter abnormal range of CAG repeat lengths and older onset age. Because of the clinical resemblance among familial parkinsonisms, we suggest that SCA2 should be excluded in cases of familial parkinsonism.

Adolescent↗

PubMed2004

The parkinsonian phenotype of spinocerebellar ataxia type 3 in a Taiwanese family.

We report a parkinsonian phenotype of spinocerebellar ataxia type 3 (SCA3) in three female sibs from one Taiwanese family, found in a genetic analysis of 60 patients from 49 families with familial parkinsonism. Initially, all three patients presented with early onset resting tremor, rigidity, bradykinesia, and good response to levodopa. In the later stages, peripheral neuropathy developed in one sib and mild ataxia in another one. Decreased concentration of dopamine transporter in the striatum was demonstrated by (99m)Tc-TRODAT-1 SPECT imaging in the two sibs studied. Therefore, SCA3 should be considered as an important etiology of familial parkinsonism.

Adult↗

PubMed2003

The expression of mammaglobin mRNA in peripheral blood of metastatic breast cancer patients as an adjunct to serum tumor markers.

We conducted a study to compare the expression of human mammaglobin (hMAM) mRNA in breast cancer patients' peripheral blood with serum carcinoembryonic antigen (CEA) and CA 15.3. A total of 33 metastatic breast cancer patients were enrolled. The blood samples were used to test the expression of hMAM mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and CEA, CA 15.3 by radioimmunoassay. The serum CEA and CA 15.3 levels were elevated in 17 (51%) and 23 (69%) of the patients, respectively. When combined CEA with CA 15.3, the sensitivity rate raised to 78%. hMAM mRNA was detected in 18 (54%) of the 33 patients. When combined hMAM mRNA with CEA or CA 15.3, the sensitivity rate were 81% and 90%, respectively (P=0.045). In conclusion, the hMAM mRNA RT-PCR can be an adjunct in detecting metastatic breast cancer.

Adult↗

PubMed2002

Dopa-responsive parkinsonism phenotype of spinocerebellar ataxia type 2.

We report on 2 brothers, Patients 1 and 2, who presented with a similar clinical syndrome consisting of resting tumor, bradykinesia, rigidity, and dysarthria at the ages of 40 and 43 years, respectively. An excellent response to levodopa therapy was observed throughout the disease course. No gait or limb ataxia, slow saccades, or decreased tendon reflexes were detected, but unsteadiness of gait with propulsion developed recently in Patient 1 approximately 25 years after disease onset. Magnetic resonance imaging demonstrated mild atrophy of the pons and cerebellum in Patient 1 and cerebellar atrophy in Patient 2. Expanded CAG repeats, numbering 36, in one allele of the ataxin-2 gene were identified in Patient 1 only; his brother was not available for this investigation. With [(99m)Tc]TRODAT-1 single photon emission computed tomography of the brain, a significant bilateral and asymmetrical reduction of striatal dopamine transporters was found in Patient 1 compared to healthy controls. This bilateral reduction of striatal dopamine transporters resembled that observed in a set of controls with Parkinson's disease who had asymmetrical impairment. These results suggest that patients with familial parkinsonism who present with typical Parkinson's disease should be screened for the genetic defect of spinocerebellar ataxia type 2. The presynaptic impairment of nigrostriatal function is very likely to be the reason for levodopa responsiveness.

Aged↗

PubMed2002

Dopamine transporter concentration is reduced in asymptomatic Machado-Joseph disease gene carriers.

UNLABELLED: Dopamine transporter (DAT) binding is decreased in Machado-Joseph disease (MJD) patients. To further investigate the DAT activity in asymptomatic MJD (aMJD) gene carriers, we performed this prospective study using (99m)Tc-TRODAT-1 ([(99m)Tc][2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]-methyl](2-mercaptoethyl)amino]ethyl]amino]ethane-thiolato(3-)-N2,N2',S2,S2]oxo-[1R-(exo-exo)])) brain SPECT on 5 aMJD gene carriers, 10 age-matched MJD patients, and 10 age-matched healthy control subjects. METHODS: Brain SPECT images were acquired 4 h after intravenous injection of 925 MBq (25 mCi) (99m)Tc-T RODAT-1, which is known to bind specifically to the DAT on the nigrostriatal terminals. By fusing these SPECT images with a striatal atlas, obtained from MRI, binding of this tracer in the entire striatum was measured and the uptake values in bilateral striatal areas were compared between these 3 groups. RESULTS: The uptake values of the aMJD gene carriers (P < 0.001) and MJD patients (P < 0.001) displayed a significant reduction compared with those of the control subjects. The reduction was more severe in the MJD patient group (P < 0.05). Bilateral putamen-to-caudate ratios were significantly lower in the aMJD gene carrier and MJD patient groups (P < 0.001). The dopamine neuronal activity, as represented by the tracer binding, was more prominently affected in the putamen in these patients and gene carriers. CONCLUSION: (99m)Tc-TRODAT-1 brain SPECT is capable of detecting early alteration of dopamine neurons in the striatal region. Significantly, the results suggest that this impairment of presynaptic dopamine function actually occurs at an early stage, which was previously unrecognized in these aMJD gene carriers.

Adult↗