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Biomedical subjects

E K Tan

Publications and source records attributed to E K Tan.

At least 37 records · Page 2Linked to original sources
PubMed2005

The G2019S LRRK2 mutation is uncommon in an Asian cohort of Parkinson's disease patients.

A common heterozygous leucine-rich repeat kinase 2 (LRRK2) mutation 6055G > A transition (G2019S) accounts for about 3-7% of familial Parkinson's disease (PD) and 1-1.6% sporadic PD in a number of European populations. To determine the prevalence of the G1019S mutation in our Asian population, we conducted genetic analysis of this mutation in 1000 PD and healthy controls. The G2019S mutation was not detected in any of our study subjects. The prevalence of G2019S mutation is rare (< 0.1%) in our population, suggesting that occurrence of this mutation may vary amongst different ethnic races. This has important clinical implication when implementing guidelines for genetic testing.

Adolescent↗
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↗
PubMed2005

Hemidystonia precipitated by acute pontine infarct.

Hemidystonia is frequently due to an underlying structural lesion in the basal ganglia and thalamus. It has been suggested that a preserved corticospinal tract may be required for hemidystonia to manifest. We provide the first report of a patient who presented with rapid-onset hemidystonia precipitated by an acute pontine infarct demonstrated on diffusion-weighted magnetic resonance imaging. Acute dysregulation of pallidal efferents to the pedunculopontine and/or pontine afferents to the thalamus may precipitate hemidystonia.

Adult↗
PubMed2005

A variant in the HS1-BP3 gene is associated with familial essential tremor.

BACKGROUND: Genetic linkage studies have identified two susceptibility loci for essential tremor (ET) on chromosomes 3q13 (ETM1) and 2p24.1 (ETM2). Linkage disequilibrium studies in separate population samples from the United States and Singapore suggest an association between ET and loci at ETM2. METHODS: Fine mapping studies were conducted on multiplex and singleton US families linked to ETM2 using newly detected loci within the candidate interval to establish the minimal critical region (MCR) harboring an ET gene. The genes and transcripts within this interval were systematically analyzed by single-strand conformational polymorphism analysis and DNA sequencing. RESULTS: A 464-kb region between loci D2S2150 and etm1231 was defined as the MCR. The coding regions and flanking intronic splice sites of two genes and seven transcripts in this interval were evaluated for mutations. A missense mutation (828C-->G) in the transcript FLJ14249 (HS1-BP3) was identified in one US family. This mutation was found in another apparently unrelated US family with ET and was absent in 150 control samples (300 chromosomes). The 828C-->G mutation causes a substitution of a glycine for an alanine residue in the HS1-BP3 protein. The HS1-BP3 protein binds to proteins that are highly expressed in motor neurons and Purkinje cells and regulate the Ca2+/calmodulin-dependent protein kinase activation of tyrosine and tryptophan hydroxylase. CONCLUSIONS: A rare variant in the HS1-BP3 gene that is associated with essential tremor (ET) in two families is reported. This finding will facilitate research on the functional role of this gene and related genes in the pathogenesis of ET.

Adult↗
PubMed2005

Smad3 signalling plays an important role in keloid pathogenesis via epithelial-mesenchymal interactions.

Smad signalling plays important roles in developmental and cancer biology as well as in fibropathogenesis. Its role in keloid biology is not known. Epithelial-mesenchymal interactions, originally described in normal skin, have recently been established to play a significant role in keloid pathogenesis, and demonstrate the important influence of keratinocyte paracrine factor signalling on fibroblast behaviour. The present study investigated the role of downstream Smad cascade induction in this interaction. Normal fibroblasts (NF) and keloid fibroblasts (KF) were co-cultured in serum-free medium with normal keratinocytes (NK) or keloid keratinocytes (KK) for 5 days, after which fibroblast cell lysates were subjected to western blot and immunoprecipitation analysis to quantify the levels of Smad and Smad2/3/4 binding complex. In another set of experiments, wild-type (wt), Smad2-null (Smad2-/-) and Smad3-null (Smad3-/-) mouse embryonic fibroblasts (MEF) were assayed for cell proliferation and collagen production after serum-free co-culture with KK or exposure to conditioned media collected from serum-free KK/KF co-culture. Compared to normal skin, keloids expressed high basal levels of TGFbetaR1 and TGFbetaR2, Smad2, 3 and 4 and phospho-Smad2. Upregulation of TGFbetaR1 and TGFbetaR2, Smad3 and p-Smad2 was observed in KF co-cultured with KK, together with enhanced Smad3 phosphorylation and Smad2/3/4 binding complex production. When MEF-wt, MEF-Smad2-/- or MEF-Smad3-/- were co-cultured with KK or exposed to KK/KF co-culture conditioned media, enhanced proliferation and collagen production were seen in MEF-wt and MEF-Smad2-/- but not in MEF-Smad3-/- cells. The activation of Smad signalling, importantly that of Smad3, appears to be one facet of the complex epithelial-mesenchymal interactions in keloid pathogenesis, resulting in active KF proliferation and collagen-ECM production in co-culture with KK. This finding suggests the suppression of Smad signalling as a novel approach in keloid therapy.

Adolescent↗
PubMed2005

Evaluation of cell culture on the polyurethane-based membrane (Tegaderm): implication for tissue engineering of skin.

BACKGROUND: The use of polymer-based delivery systems, on which cells are cultured and transferred, improves the ease of handling and transfer of the keratinocytes. A transparent polymer also allows observation of cell growth prior to grafting as well as re-epithelialization after grafting to the wound. We have developed techniques for cultured keratinocytes on Tegaderm (3M), an inexpensive and easily available polyurethane-based wound dressing, for treatment of burn and chronic wounds. In this study, we evaluate cell culture characteristics of three different cell types, human epidermal keratinocytes, human dermal fibroblasts and pig bone marrow mesenchymal stem cells on Tegaderm membrane. METHODS: Cells were isolated from human skin or pig bone marrow and cultured on membranes for a period of five days. Cell proliferation was assessed by colorimetric assay (MTT) and scanning electron microscopy. RESULTS AND CONCLUSIONS: This study confirms that Tegaderm membranes support attachment and growths for these cell types, with those growth characteristics are similar, if not as good as that of optimal condition of tissue culture plastics. Data from our study suggest that Tegaderm membranes can be used, modified and developed further as an economical and easily available material for tissue engineered skin.

Animals↗
PubMed2005

Non-motor manifestations in essential tremor: use of a validated instrument to evaluate a wide spectrum of symptoms.

INTRODUCTION: Recent studies suggest an association between non-motor symptoms and essential tremor (ET). Few studies have assessed psychological symptoms in ET. These studies were limited to western white populations and utilized scales that were specific to only one or two psychiatric domains. By contrast, the Symptom Checklist-90R (SCL-90R) is a validated clinical scale to screen for symptoms related to a spectrum of nine different psychological domains. OBJECTIVE: To determine whether a wide spectrum of non-motor manifestations is associated with ET in patients in an Asian cohort. METHODS: Consecutive ET patients and a group of control subjects were evaluated using the SCL-90R, which is comprised of items in nine major symptom dimensions and three global indices, including the positive symptom distress index. RESULTS: ET patients (N = 84) and controls (N = 78) were similar in age (50.0+/-18.0 vs 46.0+/-14.4 years), gender and other demographic variables. ET patients had higher scores in three of nine major symptom dimensions: anxiety, phobic anxiety (p < 0.0005) and psychoticism (p = 0.005). In multivariate analysis, the anxiety (p < 0.0005) and the positive symptom distress index scores (p < 0.0005) were greater in ET patients compared to controls after adjusting for sex, age, marital status and educational level. The severity, but not duration of ET was correlated with the severity of anxiety symptoms. CONCLUSIONS: Utilizing the SCL-90R, we highlighted that ET patients reported more non-motor symptoms than healthy controls. The more frequent occurrence of anxiety symptoms in our Asian cohort extends the observation that such non-motor manifestations should be considered in the clinical management of ET.

Adult↗
PubMed2005

Prescribing pattern in Parkinson's disease: are cost and efficacy overriding factors?

Information on prescribing pattern of antiparkinsonian medications and factors influencing neurologists' choice of such drugs are important considerations in evaluating healthcare cost of Parkinson's disease (PD). We surveyed neurologists' perceived factors influencing their choice of drugs and actual prescribing pattern in PD. Three hundred and six patients at a tertiary hospital, diagnosed with idiopathic PD and who were dispensed antiparkinsonian drugs during a 6-month period were randomly selected. Patient demographics, type and dose of medications were analysed. A questionnaire survey evaluating the factors influencing choice of medications was administered to neurologists who practiced at the institution. The study population had a mean age of 64.4 years (SD +/- 9.9 years), and more than 80% were at Hoehn & Yahr stage 2-3. 92.3% of the study population were receiving levodopa and monotherapy, with levodopa being the most common treatment regimen. Patients who were prescribed levodopa were significantly older and at a later stage of disease compared to those without levodopa (p < 0.05). Only 26.8% of patients were prescribed dopamine agonists. In the survey, the neurologists cited severity of symptoms, and patients' intolerance of side effects, and efficacy as the most important factors influencing their choice of drugs. However, the actual prescribing pattern revealed a strong positive correlation of drug usage with cost subsidy by the institution. While factors affecting drug usage in PD are well recognised, cost and efficacy of a drug appear to be overriding practical factors in influencing usage pattern in clinical practice.

Aged↗
PubMed2005

Validation of a short disease specific quality of life scale for hemifacial spasm: correlation with SF-36.

BACKGROUND: A short, practical, and validated quality of life (QoL) scale for hemifacial spasm (HFS) is not currently available. OBJECTIVES: To examine the reliability and validity of a short self-rating scale (HFS-7) by comparing HFS patients with healthy controls. We also evaluated the correlation of HFS-7 with the physical and mental domains of SF-36, a generic QoL scale. METHODS: Seven self-rating items (HFS-7) were administered to HFS patients and healthy controls. In addition, HFS patients answered the SF-36 questionnaire. The validity and reliability of HFS-7 were analysed and correlation between HFS-7 and SF-36 examined. RESULTS: A total of 178 subjects were enrolled in the study, including 85 HFS patients with mean age of 54.8 (SD 11.0) years, of whom 52 (61.2%) were women, and 93 controls with mean age of 51.4 (SD 10.0) years, of whom 59 (63.4%) were women. The test-retest intraclass correlation coefficient for the seven items was between 0.75 and 0.90 and Cronbach's coefficient of reliability for the HFS-7 scale was 0.88. Every item in HFS-7 discriminated between disease and controls (p<0.0001). The HFS-7 summary index correlated with the SF-36 summary score (Spearman's correlation r = -0.28, p = 0.009), in particular the mental health summary score (r = -0.416, p<0.0001) and the emotional domain (r = -0.466, p<0.00001). CONCLUSION: HFS-7 could prove useful as a simple clinical tool to assess and monitor QoL measures in HFS patients.

Adult↗
PubMed2004

Fragile X premutation alleles in SCA, ET, and parkinsonism in an Asian cohort.

Among 367 subjects, the authors analyzed 167 patients with essential tremor, sporadic progressive cerebellar ataxia, multiple-system atrophy, and atypical parkinsonism and 200 healthy control subjects for FMR1 premutation alleles. None of the subjects carried alleles within the premutation range. These findings suggest that in the absence of other supportive clinical or imaging features, the cost-effectiveness of routine fragile X tremor/ataxia syndrome screening in this Asian cohort with movement disorders was low.

Adult↗
PubMed2004

Alpha-synuclein haplotypes implicated in risk of Parkinson's disease.

The authors examined four- and six-loci haplotype constructs (from five single nucleotide polymorphisms and three microsatellite regions) of the alpha-synuclein gene in patients with Parkinson's disease (PD) and controls in an ethnic Chinese population. Logistic regression analysis demonstrated an association of NACP-Rep1 (p = 0.002) and L478 (p < 0.0001) with risk of PD after correction for the effects of age, sex, and the other polymorphic loci. Specific four-loci and six-loci haplotypes were significantly associated with an increased or decreased risk of PD.

Adult↗
PubMed2004

Diagnosis and misdiagnosis of hemifacial spasm: a clinical and video study.

Early recognition of hemifacial spasm (HFS) is important as it can be effectively treated. 203 family physicians participated in a video "test" on HFS. Only 9.4% (19/203) were able to diagnose HFS. 94 (46.3%) of them did not know how to manage the condition. Twenty-two (10.8%) would use steroids as a treatment and 13 (6.4%) felt no treatment was needed. Only 27 (13.3%) indicated that botulinum toxin could be employed to treat HFS. The year of graduation of the doctors significantly correlated with a correct diagnosis (P<0.05). The low positive diagnostic rate (25.7%) of HFS from referrals to the movement disorder clinic corroborated findings from the video test.

Adult↗
PubMed2004

Restless legs symptoms in thyroid disorders.

Dopaminergic dysfunction is associated with thyroid disorders and restless legs syndrome (RLS). In a 'face-to-face' interview, we evaluated for RLS using the diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG) in patients diagnosed biochemically with either hyper- or hypothyroidism, and in controls without thyroid disorders. Amongst 146 consecutive patients with biochemically confirmed thyroid disorders, none satisfied all the IRLSSG criteria of RLS, similar to the control population (0.2%, 1/434). However, we found 8.2% (12/146) with RLS-like symptoms (satisfied the first 3 IRLSSG criteria) compared to 0.9% (4/434) in the controls (p < 0.0001). Four (33.3%) of these patients reported complete resolution of these symptoms after treatment for their thyroid condition. In conclusion, while RLS-like symptoms were observed in some patients with thyroid disorders, our study demonstrates no significant difference of RLS prevalence between patients with thyroid disorders and euthyroid controls.

Adolescent↗
PubMed2004

Haplotype analysis at the ETM2 locus in a Singaporean sample with familial essential tremor.

An ancestral haplotype on chromosome 2p24.1 described in an American sample with familial essential tremor (ET) was analyzed in a different ethnic sample from Singapore. Six polymorphic loci (etm1240, etm1231, etm1234, APOB, etm1241, and etm1242) in a 274-kb interval within an ET gene candidate region (ETM2) were analyzed in Singaporean individuals with a family history of ET (n = 52) and compared to Singaporean controls older than age 65 (n = 49). The allele frequencies were significantly different between cases and controls for the loci etm1234 (p = 0.0001) and APOB (p = 0.0320). An extended haplotype formed by the loci etm1231, etm1234, and APOB occurred with a frequency of 31% in Singaporean cases and in 1.8% of elderly Singaporean controls (p = 0.0005). Haplotype studies in two different population samples suggest that a disease locus for ET lies near or within the 100-kb interval between the loci etm1231 and APOB.

Adolescent↗
PubMed2004

Restless hand symptoms in carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is a nerve entrapment disorder, involving the median nerve when it passes the carpal tunnel at the wrist. Using a case-control methodology, 312 electrophysiologically confirmed CTS patients with mean age of 51.3+/-9.4 (27-74) years (81.7% women) and 100 controls with mean age of 50.4+/-9.2 (21-88) years (75% women) were examined utilising a questionnaire similar to the clinical diagnostic criteria of restless legs syndrome (RLS). Forty-four (14.1%) of the CTS patients have symptoms compatible with restless hand syndrome compared with none (0%) in the control group (p < 0.0001). The severity of CTS was not significantly associated with the motor restlessness. Our observations suggest that entrapment syndromes such as CTS can be associated with a form of restlessness in the hands, analogous to RLS.

Adult↗