Biomedical subjects

Seng-Sheen Fan

Publications and source records attributed to Seng-Sheen Fan.

10 recordsLinked to original sources

PubMed2006

Polymorphism in the IL-1alpha (-889) locus associated with elevated risk of primary open angle glaucoma.

PURPOSE: Recent laboratory evidence indicates that the inflammatory cytokine, interleukin-1 (IL-1), has either protective or adverse effects on primary open angle glaucoma (POAG). Inheritance of the IL-1alpha (-889) polymorphism (the T allele), previously shown to increase IL-1 production, has been associated with an elevated risk of Alzheimer's disease. The neuronal injuries associated with Alzheimer's disease have a number of similarities with the optic nerve changes often seen with POAG. In this report we have explored the possible association between the IL-1alpha (-889) polymorphism and the development of POAG. METHODS: Chinese patients with POAG (156) were recruited and compared with 167 healthy chinese controls. Genomic DNA was amplified by polymerase chain reaction, followed by enzymatic restriction fragment length polymorphism technique (PCR-RFLP). Patients and controls were genotyped for the C/T polymorphism at position -889 of the IL-1alpha gene promoter region. RESULTS: The frequency of the IL-1alpha (-889) T allele (21% versus 13%, respectively; p=0.007) and the carriers of the IL-1alpha (-889) T allele (37% versus 25%; p=0.019, OR 1.76, 95%CI 1.1-2.83) were greater in POAG patients compared with controls. There is a higher risk of POAG associated with homozygosity for the IL-1alpha (-889) T allele (TT genotype) compared with the control population (CC genotype; 5% versus 1%, respectively, p=0.04; OR 5.1, 95% CI 1.19-21.66). CONCLUSIONS: The IL-1alpha (-889) T allele polymorphism, previously shown to increase IL-1 gene expression, may be a risk factor in the development of POAG.

Adult↗

PubMed2006

The TGFbeta1 gene codon 10 polymorphism contributes to the genetic predisposition to high myopia.

PURPOSE: Transforming growth factor-beta (TGFbeta), a multifunctional growth factor that plays a key role in the remodeling of scleral tissue, may be involved in the predisposition and pathophysiology of high myopia. Our aim was to examine the association between myopia and the polymorphisms within codon 10 of the TGFbeta1 gene. METHODS: This was a case control study. The study group contained participants who had high myopia and a spherical equivalent greater than -6.00 D. The control group was composed of medical students whose spherical equivalent was less then -0.5 D. All volunteers in this study were over 16 years old and had never undergone ocular surgery. Genotyping was conducted by restriction fragment length polymorphism, and the results were compared between myopia patients and control subjects. RESULTS: The frequency of the CC genotype in TGFbeta1 codon 10 differed significantly between patients in the high myopia group (n=201) and individuals in the control group (n=86; p<0.001). People with either the CT or TT genotype had a lower probability of having high myopia with a spherical equivalent greater than -6.00 D than those with the CC genotype. Furthermore, there was a higher frequency of the C allele in the high myopia group than with the control group (p<0.001, OR=1.83, CI=1.27-2.63). CONCLUSIONS: The frequency of the CC homozygote in the high myopia group was much higher than in the control group, indicating people with the CC homozygote may be at a higher risk of developing high myopia. Varied expression of this gene may contribute to the genetic predisposition to high myopia in Chinese Taiwanese.

Adolescent↗

PubMed2006

The role of Ca2+ on the DADS-induced apoptosis in mouse-rat hybrid retina ganglion cells (N18).

Diallyl disulfide (DADS), a component of garlic, has been shown to induce growth inhibition and apoptosis in human cancer cell types. The present studies were designed to investigate the effects of DADS on mouse-rat hybrid retina ganglion cells (N18) to better understand its effect on apoptosis and apoptosis-related genes in vitro. Cell viability, cell cycle analysis, reactive oxygen species (ROS), Ca2+ production, mitochondria membrane potential, apoptosis induction, associated gene expression and caspases-3 activity were examined by flow cytometric assay and/or Western blot. After 24-h treatment with DADS, a dose- and time-dependent decrease in the viability of N18 cells was observed and the approximate IC50 was 27.6 microM. The decreased percentage of viable cells are associated with the production of ROS then followed by the production of Ca2+ which is induced by DADS. DADS induced apoptosis in N18 cells via the activation of caspase-3. DADS increased the protein levels of p53, cytochrome c and phosphated JNK within 24 h of treatment and it decreased the levels of Bcl-2 and those factors may have led to the mitochondria depolarization of N18 cells. DADS induced apoptosis were accompanied by increased levels of Ca2+ and decreased mitochondrial membrane potential which then led to release the cytochrome c, cleavage of pro-caspase-3. Deleted levels of Ca2+ by BAPTA-AM 10 microM (intracellular calcium chelator) then led to decrease DADS-induced apoptosis. Inhibition of caspase-3 activation by inhibitor (z-VAD-fmk) completely blocked DADS-induced apoptosis on N18 cells. The results indicated that oxidative stress modulates cell proliferation and Ca2+ modulates the cell death induced by DADS.

Allyl Compounds↗

PubMed2005

Association of E-cadherin gene 3'-UTR C/T polymorphism with primary open angle glaucoma.

PURPOSE: E-cadherin (E-CDH) is one of the most important cell surface glycoproteins involved in cell morphogenesis. In primary open angle glaucoma (POAG), the extracellular matrixes of trabecular meshwork and lamina cribrosa in the optic nerve head are out of balance. We suspected that E-CDH by way of metalloproteinases is closely related to POAG. We therefore investigated the relationship between CDH-1 gene 3' untranslated region (3'-UTR) polymorphism and POAG patients in order to support this hypothesis. PATIENTS AND METHODS: We enrolled 60 POAG patients and 103 healthy volunteers from the Department of Ophthalmology at the China Medical University Hospital, Taichung, Taiwan, ROC. None of the control subjects had a history of eye disease and all underwent the same examination as the POAG patients. PCR-based analysis of the restriction fragment length polymorphism was used to test the CDH-1 gene 3'-UTR polymorphism. All statistical analyses were performed by the chi(2) test. RESULT: There was a significant difference in the distribution of the CDH-1 gene 3'-UTR C/T polymorphism between POAG patients and the normal controls (p <0.000). The odds ratio of the 'C' allele was al so significantly different between both groups (odds ratio = 5.510, 95% confidence interval = 3.171-9.574). CONCLUSION: CDH-1 is closely related to metalloproteinase and plays an important but not well-understood role in the onset and progression of POAG. The exact role of CDH-1 in POAG could be resolved by the posttranslated products of the gene and the protein-protein interaction of the gene products in the future.

3' Untranslated Regions↗

PubMed2005

Using Drosophila eye as a model system to characterize the function of mars gene in cell-cycle regulation.

Human hepatoma up-regulated protein (HURP), a cell-cycle regulator, is found consistently overexpressed in human hepatocellular carcinoma. At present, the function of HURP in cell-cycle regulation and carcinogenesis remains unclear. In database mining, we have identified a mars gene in Drosophila, which encodes a protein with a high similarity to HURP in its guanylate kinase-associated protein (GKAP) motif. Overexpression but not down-regulation of mars in eye discs resulted in a higher mitotic index along with a high frequency of mitotic defects, including misalignment of chromosomes and mispositioned centrosomes, at the second mitotic wave (SMW). The consequence of mitotic defects impairs cell-cycle progression, and causes cell death posterior to the furrow. Immunocytochemical studies also have indicated that the expression of Mars is cell cycle regulated, and that its subcellular localization is dynamically changed during cell-cycle progression. Furthermore, we also demonstrated that the first 198 amino acids at the N-terminus of Mars are responsible for the degradation of Mars in non-mitotic cells. Together, we report the use Drosophila eye as a model system to characterize the function of the mars gene in cell-cycle regulation.

Amino Acid Motifs↗

PubMed2005

Distribution of oxidation enzyme eNOS and myeloperoxidase in primary open angle glaucoma.

Genetic factors and the influence of superoxide are known to play roles in the etiology of glaucoma. We evaluated the association between primary open angle glaucoma (POAG) and two polymorphisms in the epithelial nitric oxide synthase (eNOS) gene, and one polymorphism in the myeloperoxidase (MPO) gene. We enrolled 66 patients with POAG and 100 healthy volunteers in this study. The polymorphisms in the eNOS and the polymorphism MPO -463 G-to-A in the MPO gene were resolved by polymorphism polymerase chain reaction (PCR). There were no significant differences in the distribution of the eNOS intron -4 (P=0.481), eNOS promotor -786 (P=0.555), and MPO -463 (P=0.292) gene polymorphisms between the POAG patients and the volunteers (P-values=0.481, 0.555, and 0.292, respectively). None of the alleles from either gene differed between the groups (P-values=0.483, 0.554, and 0.183, respectively). Superoxide is closely related to glaucoma, and eNOS and MPO are two important enzymes in the free radical pathway. However, polymorphisms of the eNOS intron-4, eNOS promotor -786, and MPO -463 gene polymorphisms did not reveal significant differences between POAG patients and controls in our study. The use of these agents and other superoxide-related genes for clinical applications requires further investigation.

Adult↗

PubMed2004

Transporter associated with antigen processing gene 1 codon 333 and codon 637 polymorphisms are associated with primary open-angle glaucoma.

INTRODUCTION: Genetic factors in the immune system are widely suspected to have a role in the etiology of glaucoma. In this study, we evaluated the association between primary open-angle glaucoma (POAG) and the transporter associated with antigen processing (TAP) gene polymorphisms. The TAP gene polymorphisms we evaluated were TAP1-1 codon 333 A/G (Ile-Val), TAP1-2 codon 637 (Asp-Gly), TAP2-1 codon 379 (Val-Ile), TAP2-2 codon 665 (Thr-Ala) and codon 687 (Stop-Gln), and TAP2-3 codon 565 (Ala-Tht). Due to the lack of predictive markers for glaucoma, many glaucoma patients are only diagnosed when their visual acuity and visual field has irreversibly deteriorated. Our aim was to confirm whether or not the TAP1 and TAP2 genes can be used to identify suspectability to glaucoma. METHODS: Sixty-six patients with POAG and 105 healthy volunteers were enrolled in this case-control study. We resolved the TAP1 and TAP2 gene polymorphisms by PCR-based analysis. RESULTS: There was a significant difference in the distribution of TAP1-1 codon 333 and TAP1-2 codon 637 gene polymorphisms (p = 0.0375 and 0.01, respectively) between POAG patients and healthy controls. However, there was no significant difference between the two groups in TAP2-1 codon 370, TAP2-2 codon 665, and TAP2-3 codon 565 (p = 0.273, 0.19, and 0.131, respectively). In TAP1-1 codon 333, there was a significant difference between the "GG" homozygote and "GA" heterozygote (OR 4.32; 95% CI 1.336, 13.969). In TAP1-2 codon 637, there was a significant difference between the "GG" homozygote and "GA" heterozygote (OR 15; 95% CI 1.733, 129.860). There was also a significant difference between "GG" homozygote and "AA" homozygote (OR 10.8; 95% CI 1.286, 91.880). Therefore, TAP1-1 codon 333 and TAP1-2 codon 637 gene polymorphisms were useful genetic markers of POAG. The prevalence of the TAP1-2 "GG" homozygote differs significantly between POAG patients and healthy controls, although in the alleles of the both TAP genes, there were no significant differences between the two groups. CONCLUSION: The immune system acts as an arbiter to help determine whether under stress a neuronal cell will survive or sacrifice itself to injuries. TAP1-1 and TAP1-2 play an important role in the immune system. TAP1-1 and TAP1-2 gene polymorphisms may, by way of post-transcriptional changes and altered regulation of gene expression, be involve the immune system in the development of POAG.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Insulin-like growth factor-II gene polymorphism is associated with primary open angle glaucoma.

Hypoxia and ischemia play important roles in the onset and progression of glaucoma. Insulin-like growth factors (IGF) are important neurotrophic agents that respond to hypoxia-ischemia. In this study, we enrolled 60 primary open angle glaucoma (POAG) patients and 104 healthy volunteers from the China Medical College Hospital. Among the polymorphism of IGFs gene, exon 9 Apa I C/T gene polymorphism is the most frequently seen. The polymorphism was observed following polymerase chain reaction based restriction analysis used to to resolve the relationship between IGF-II exon 9 Apa I C/T gene polymorphism and POAG. The distribution of the IGF-II exon 9 gene polymorphism showed statistical differences in the distribution of genotype frequencies between POAG patients and normal controls (P=0.010). The odds ratio of C/C homozygote was 0.266 (95% confidence interval=0.636 approximately 0.111). IGF-II is an important neurotrophic agent and regulates the suffering of POAG. C/C homozygote of IGF-II exon 9 Apa I C/T gene polymorphism is a useful marker of POAG in Chinese.

Adult↗

PubMedDate not supplied

Dynactin affects extension and assembly of adherens junctions in Drosophila photoreceptor development.

Drosophila eye development is a progressive process including cell fate determination, pattern formation, and rhabdomere morphogenesis. During eye development, a dramatic change in cell shape, which involves turning and extension of the photoreceptor apical surface, occurs in the early pupal stages. It is known that assembly and extension of adherens junctions (AJs) play an important role in this process. In the present study, I show that mutation of the largest subunit of dynactin complexes encoded by Glued (Gl) affects the extension and assembly of Ajs in developing photoreceptors. In Gl(1)/(+) mutants and transgenic flies expressing the dominant negative form of Glued, the AJs failed to properly assemble and extend. In addition, the morphogenesis of rhabdomeres was also affected in these flies. Taken together, these results suggest that the extension and assembly of AJs as well as determination of the rhabdomere domain in photoreceptor development are Gl dependent.

Adherens Junctions↗

PubMedDate not supplied

Use of gain-of-function study to delineate the roles of crumbs in Drosophila eye development.

The cell polarity gene, crumbs (crb)), has been shown to participate in the development and degeneration of the Drosophila retina. Mutations in CRB1, the human homologue of Drosophila crb, also result in retinitis pigmentosa and Leber congenital amaurosis. In this study, we used the gain-of-function approach to delineate the roles of CRB in developing Drosophila eye. In the third-instar larval stage, eye development is initiated with photoreceptor differentiation and positioning of photoreceptor nuclei in the apical cellular compartment of retinal epithelium. In the pupal stage, differentiated photoreceptors begin to form the photosensitive structures, the rhabdomeres, at their apical surface. Using GMR-Gal4 to drive overexpression of the Crb protein at the third-instar eye disc, we found that differentiation of photoreceptors was disrupted and the nuclei of differentiated photoreceptors failed to occupy the apical compartment. Using HS-Gal4 to drive Crb overexpression in pupal eyes resulted in interference with extension of the adherens junctions and construction of the rhabdomeres, and these defects were stage-dependent. This gain-of-function study has enabled us to delineate the roles of Crb at selective stages of eye development in Drosophila.

Adherens Junctions↗