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Biomedical subjects

Piu Chan

Publications and source records attributed to Piu Chan.

At least 19 recordsLinked to original sources
PubMed2006

A common A340T variant in PINK1 gene associated with late-onset Parkinson's disease in Chinese.

Parkinson's disease (PD) is a complex neurodegenerative disease with genetic risk factors. Common variants in genes implicated in hereditary forms of parkinsonism may be predisposing factors for sporadic PD. Recent studies have demonstrated that mutations in PINK1 (PARK6 locus) gene, encoding PTEN-induced kinase 1, are associated with both familial recessive and sporadic early onset parkinsonism. In order to assess whether the coding variant A340T contributes to the risk of late-onset PD, we performed an association study of 539 PD patients with an onset age at or older than 50 and 525 controls in Chinese Han. Genotyping was performed by denaturing high performance liquid chromatography (DHPLC) combined with sequencing analyses. The A-allele frequency was 6.2% in PD and 4.2% in controls (p=0.0404), while G/A genotype frequencies were 12.4% in PD and 8.4% in the controls (p=0.0350). Our results yielded significant evidence for disease association between PINK1 A340T and PD with later onset (OR 1.55, 95% CI 1.04-2.32, p=0.0393), thus suggesting that PINK1 A340T variant may contribute to the risk for late-onset PD in Chinese.

Aged↗
PubMed2006

Rotigotine treatment partially protects from MPTP toxicity in a progressive macaque model of Parkinson's disease.

Clinical DA agonist monotherapy trials, which used in vivo imaging of the DA transporter (DAT) to assess the rate of progression of nigrostriatal degeneration, have failed to demonstrate consistent evidence for neuroprotection. The present study aims at reconciling these experimental and clinical data by testing the protective property of the continuously delivered D3/D2/D1 dopamine receptor agonist rotigotine. Using a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned (MPTP) macaque model that mimics the progression of Parkinson's disease in vivo ([99mTc]-TRODAT-1 single photon emission computed tomography (SPECT)) and ex vivo ([125I]-nortropane DAT labelling) endpoints were evaluated. After 38 days of treatment followed by two weeks of washout, rotigotine-treated animals were significantly less parkinsonian than the vehicle-treated ones. Such behavioural difference is the consequence of a partial protection of the DA terminals as could be confirmed by ex vivo DAT labelling. However, the protection of nerve terminals was not detected using SPECT. The data suggest that rotigotine exerts partial protection but that conventional imaging would not be able to identify such protection.

Animals↗
PubMed2006

Quantitative analysis along the pyramidal tract by length-normalized parameterization based on diffusion tensor tractography: application to patients with relapsing neuromyelitis optica.

In this study, we introduced a length-normalized parameterization method to establish anatomical correspondence of white matter fiber tracts across subjects and applied this method to investigate the presence of abnormal diffusion along the pyramidal tract (PYT) of relapsing neuromyelitis optica (RNMO) patients without visible brain lesions. In this approach, the part of the PYT between the lowest slice of the cerebral peduncle and the uppermost slice of the lateral ventricle was reconstructed to establish the anatomical correspondence across subjects using diffusion tensor tractography. Then it was parameterized by normalizing its length and dividing equally the normalized length into a certain number of segments, so that the comparability of each segment across subjects along the PYT was established. Tract-specific diffusion indices, including directionally averaged diffusivity (D(av)), fractional anisotropy (FA), primary diffusivity (lambda(1)) and transverse diffusivity (lambda(23)), were obtained from each segment. Thus, the distribution maps of these indices along the PYT were obtained. The distribution maps of D(av), FA, and lambda(23) of RNMO patients were significantly different from those of healthy controls, especially in the lower part of the PYT. The differences may be caused by secondary degeneration to lesions in the spinal cord. In conclusion, a length-normalized parameterization method is proposed to establish anatomical correspondence for the PYT. Compared with existed methods, a major merit of our method is to provide comparability across subjects along the PYT on the basis of diffusion tensor tractography and to make it possible for the quantitative analysis along the fiber tract. This method can also be used to quantitatively analyze other white matter fiber tracts between two definite anatomic landmarks in many neurological or psychiatric diseases.

Adult↗
PubMed2006

Discriminative analysis of relapsing neuromyelitis optica and relapsing-remitting multiple sclerosis based on two-dimensional histogram from diffusion tensor imaging.

It is difficult to completely differentiate patients with relapsing neuromyelitis optica (RNMO) from relapsing-remitting multiple sclerosis (RRMS) for their similarities in clinical manifestation. In this study, we proposed a novel approach, using two-dimensional histogram of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the brain derived from diffusion tensor imaging (DTI) as classification feature, to discriminate patients with RNMO from RRMS. In this approach, two-dimensional principal component analysis (2D-PCA) was used to extract feature and reduce dimensionality of matrix-formed data efficiently. Then linear discriminant analysis (LDA) was performed on these extracted features to find the best projection direction to separate patients with RNMO from RRMS. Finally, a minimum distance classifier was generated on the basis of projection scores. The correct recognition rate of our method reached 85.7%, validated by the leave-one-out method. This result was much higher than that using feature of ADC or FA separately (59.5% for ADC, 76.2% for FA). In conclusion, the proposed method on the basis of combined features is more effective for classification than those merely using the features separately, and it may be helpful in differentiating RNMO from RRMS patients.

Diffusion Magnetic Resonance Imaging↗
PubMed2006

Oxidative stress induces nuclear translocation of C-terminus of alpha-synuclein in dopaminergic cells.

Growing evidence suggests that oxidative stress is involved in the neuronal degeneration and can promote the aggregation of alpha-synuclein. However, the role of alpha-synuclein under physiological and pathological conditions remains poorly understood. In the present study, we examined the possible interaction between the alpha-synuclein and oxidative stress. In a dopaminergic cell line MES23.5, we have found that the 200microM H(2)O(2) treatment induced the translocation of alpha-synuclein from cytoplasm to nuclei at 30min post-treatment. The immunoactivity of alpha-synuclein became highly intensive in the nuclei after 2h treatment. The protein translocated to nucleus was a 10kDa fragment of C-terminus region of alpha-synuclein, while full-length alpha-synuclein remained in cytoplasm. Thioflavine-S staining suggested that the C-terminal fragment in the nuclei has no beta-sheet structures. Our present results indicated that 200microM H(2)O(2) treatment induces the intranuclear accumulation of the C-terminal fragment of alpha-synuclein in dopaminergic neurons, whose role remains to be investigated.

Active Transport, Cell Nucleus↗
PubMed2006

Isolation and in vitro characterization of pancreatic progenitor cells from the islets of diabetic monkey models.

Recent studies on the identification of stem/progenitor cells within adult mouse and human pancreatic islets have raised the possibility that autologous transplantation might be used in treating type 1 diabetes. However, it is not yet known whether such stem/progenitor cells are impaired in type 1 diabetic patients or diabetic animal models. The latter would also allow us to test the efficacy of autologous transplantation in large animal models prior to clinical applications. The present study aims to determine the existence of stem/progenitor cells in the islets of diabetic monkey models and to assess the proliferation and differentiation potential of such cells in vitro. Our results indicate that there are pancreatic progenitor cells in the adult pancreatic islets in both normal and type 1 diabetic monkeys. The isolated pancreatic progenitor cells can be greatly expanded in culture. Upon the removal of growth medium, these cells spontaneously form islet-like cell clusters, which could be further induced to secrete insulin by inductive factors. Furthermore, the secretion of insulin and C-peptide from the islet-like cell clusters responds to glucose and other stimuli, indicating that the differentiated cells not only resemble beta-cells but also possess the unique biological function of beta-cells. This study provides a foundation for further characterization of adult pancreatic progenitor cells and autologous transplantation using pancreatic progenitor cells in treating diabetic monkeys.

Animals↗
PubMed2005

Association between acyl-coenzyme A: cholesterol acyltransferase gene and risk for Alzheimer's disease in Chinese.

There is a compelling body of evidence indicating an association between cholesterol and Alzheimer's disease (AD). Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1), an endoplasmic-reticulum-resident enzyme that catalyses the formation of cholesteryl esters (CEs) from cholesterol and long-chain fatty acids, modulates the generation of beta amyloid peptide (Abeta). A single nucleotide polymorphism rs1044925 in the sterol O-acyltransferase 1 (SOAT1), the gene encoding ACAT1, has been reported to be association with an increased risk for sporadic AD (SAD) in European population. In the present study, we examined the association of the SOAT1 rs1044925 polymorphism with SAD in our northern Han-Chinese (107 cases, 118 age and gender-matched controls) sample using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. There was no genotypic (chi(2)=0.030, OR 0.942, 95% CI=0.478-1.857) or allelic (chi(2)=0.021, OR 0.955, 95% CI=0.508-1.794) association between SAD and controls, even when the data were stratified by APOEvarepsilon4 carrier status. Our results indicate that the polymorphism rs1044925 in the 3'UTR of SOAT1 gene does not affect the risk of SAD in the northern Han-Chinese.

3' Untranslated Regions↗
PubMed2005

Alpha-synuclein and dopamine metabolism.

alpha-Synuclein (alpha-Syn), a 140-amino-acid protein richly expressed in presynaptic terminals in the central nervous system, has been shown to play a central role in the pathogenesis of Parkinson's disease. Although the normal functions of alpha-Syn remain elusive, accumulating evidence shows that the molecule is involved in multiple steps related to dopamine metabolism, including dopamine synthesis, storage, release, and uptake. The regulatory effect of alpha-Syn on dopamine metabolism is likely to tone down the amount of cytoplasmic dopamine at nerve terminals, thereby limiting its conversion to highly reactive oxidative molecules. Formation of alpha-Syn protofibrils triggered by factors such as gene mutations and environmental toxins can make the molecule lose its normal functions, leading to disrupted homeostasis of dopamine metabolism, increased cytoplasmic dopamine levels, and enhanced oxidative stress in dopaminergic neurons. The enhanced oxidative stress will, in turn, exacerbate the formation of alpha-Syn protofibrils and drive the neurons into a vicious cycle, which will finally result in the selective degeneration of the dopaminergic neurons associated with Parkinson's disease.

Animals↗
PubMed2004

Inhibition of tyrosine hydroxylase expression in alpha-synuclein-transfected dopaminergic neuronal cells.

Although the aberrant expression of alpha-synuclein (alpha-Syn) is toxic to dopaminergic neurons, little is known about the correlation between the abnormality of alpha-Syn and the expression of tyrosine hydroxylase (TH), a rate-limiting enzyme for the synthesis of dopamine neurotransmitter. In this study, the MES23.5 rat dopaminergic cell line transfected with wild-type human alpha-Syn cDNA (h alpha-Syn) construct was used to investigate the association between alpha-Syn and TH. Immunocytochemical staining and Western blot for TH showed that the TH expression was greatly decreased in h alpha-Syn-transfected cells. Northern blot confirmed that the TH mRNA level was also dramatically reduced. Reduction of TH protein levels did not affect the growth and proliferation of the transfected cells. No apparent cell injury or death was observed. These results suggest that an abnormal expression of alpha-Syn may inhibit TH synthesis in dopaminergic cells.

Animals↗
PubMed2003

Association between genetic variation of CACNA1H and childhood absence epilepsy.

Direct sequencing of exons 3 to 35 and the exon-intron boundaries of the CACNA1H gene was conducted in 118 childhood absence epilepsy patients of Han ethnicity recruited from North China. Sixty-eight variations have been detected in the CACNA1H gene, and, among the variations identified, 12 were missense mutations and only found in 14 of the 118 patients in a heterozygous state, but not in any of 230 unrelated controls. The identified missense mutations occurred in the highly conserved residues of the T-type calcium channel gene. Our results suggest that CACNA1H might be an important susceptibility gene involved in the pathogenesis of childhood absence epilepsy.

Age of Onset↗