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1.  Down-modulation of nucleoporin RanBP2/Nup358 impaired chromosomal alignment and induced mitotic catastrophe 
Cell Death & Disease  2013;4(10):e854-.
Chromosomal missegregation is a common feature of many human tumors. Recent studies have indicated a link between nucleoporin RanBP2/Nup358 and chromosomal segregation during mitosis; however, the molecular details have yet to be fully established. Observed through live cell imaging and flow cytometry, here we show that RNA interference-mediated knockdown of RanBP2 induced G2/M phase arrest, metaphase catastrophe and mitotic cell death. Furthermore, RanBP2 down-modulation disrupted importin/karyopherin β1 as well as the expression and localization of the Ran GTPase activating protein 1. We found that N-terminal of RanBP2 interacted with the N-terminal of importin β1. Moreover, at least a portion of RanBP2 partially localizes at the centrosome during mitosis. Notably, we also found that GTPase Ran is also involved in the regulation of RanBP2–importin β1 interaction. Overall, our results suggest that mitotic arrest and the following cell death were caused by depletion of RanBP2. Our findings point to a crucial role for RanBP2 in proper mitotic progression and faithful chromosomal segregation.
PMCID: PMC3824679  PMID: 24113188
RanBP2; Nup358; importin; karyopherin; centrosome
3.  Effect of Bio-Oss® Collagen and Collagen Matrix on Bone Formation 
to compare the amount of new bone produced by Bio-Oss® Collagen to that produced by collagen matrix in vivo.
eighteen bone defects, 5mm by 10mm were created in the parietal bone of 9 New Zealand White rabbits. 6 defects were grafted with Bio-Oss® Collagen. 6 defects were grafted with collagen matrix alone (positive control) and 6 were left empty (negative control). Animals were killed on day 14 and the defects were dissected and prepared for histological assessment. Quantitative analysis of new bone formation was made on 100 sections (50 sections for each group) using image analysis.
A total of 339% more new bone was present in defects grafted with Bio-Oss® Collagen than those grafted with collagen matrix (positive control). No bone was formed in the negative control group.
Bio-Oss® Collagen has the effect of stimulating new bone formation locally compared with collagen matrix in vivo. Bio-Oss® Collagen may be utilized as a bone graft material.
PMCID: PMC2866303  PMID: 20461225
Bone graft; Collagen; Bio-Oss® Collagen.
4.  Association of BANK1 and TNFSF4 with systemic lupus erythematosus in Hong Kong Chinese 
Genes and Immunity  2009;10(5):414-420.
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Recently, single nucleotide polymorphisms (SNPs) in BANK1 and TNFSF4 have been shown to be associated with SLE in Caucasian populations, but it is not known whether they are also involved in the disease in other ethnic groups. Recent data from our genome-wide association study (GWAS) for 314 SLE cases and 920 controls collected in Hong Kong identified SNPs in and around BANK1 and TNFSF4 to be associated with SLE risk. On the basis of the results of the reported studies and our GWAS, SNPs were selected for further genotyping in 949 SLE patients (overlapping with the 314 cases in our GWAS) and non-overlapping 1042 healthy controls. We confirmed the associations of BANK1 and TNFSF4 with SLE in Chinese (BANK1, rs3733197, odds ratio (OR)=0.84, P=0.021; BANK1, rs17266594, OR=0.61, P=4.67 × 10−9; TNFSF4, rs844648, OR=1.22, P=2.47 × 10−3; TNFSF4, rs2205960, OR=1.30, P=2.41 × 10−4). Another SNP located in intron 1 of BANK1, rs4522865, was separately replicated by Sequenom in 360 cases and 360 controls and was also confirmed to be associated with SLE (OR=0.725, P=2.93 × 10−3). Logistic regression analysis showed that rs3733197 (A383T in ankyrin domain) and rs17266594 (a branch point-site SNP) from BANK1 had independent contributions towards the disease association (P=0.037 and 6.63 × 10−8, respectively). In TNFSF4, rs2205960 was associated with SLE independently from the effect of rs844648 (P=6.26 × 10−3), but not vice versa (P=0.55). These findings suggest that multiple independent genetic variants may be present within the gene locus, which exert their effects on SLE pathogenesis through different mechanisms.
PMCID: PMC2834352  PMID: 19357697
SLE; BANK1; TNFSF4; Chinese; genetic association
5.  Effect of Quercetin on Preosteoblasts and Bone Defects 
Quercetin is a flavonol, also a phytoestrogen, available commonly in onion and apple. Our laboratory investigated its effect on MC3T3-E1 cells’ alkaline phosphatase activity in vitro and compared the amount of new bone produced by quercetin in collagen matrix to that produced by bone grafts and collagen matrix in vivo. Four bone defects, 5mm by 10mm were created in the parietal bone of 2 New Zealand White rabbits. In the experimental animal, 2 defects were grafted with quercetin solution mixed with collagen matrix. In the control animal, 2 defects were grafted with collagen matrix alone. Animals were killed on day 14 and the defects were dissected and prepared for histological qualitative assessment. Results showed that 10μM of quercetin increased alkaline phosphatase activity of MC3T3-E1 cells at 72 hours in vitro by 32%. In the experimental animal, there was new bone growing inside the bone defects. In conclusion, specific concentration of quercetin increased alkaline phosphatase activity of MC3T3-E1 cells in vitro and quercetin in collagen matrix has the effect of forming new bone across bone defects in vivo.
PMCID: PMC2685048  PMID: 19461927
Bone repair; flavonol; phytoestrogen; quercetin.
6.  Local Massage with Topical Analgesic, a Novel Treatment Modality for Temporomandibular Muscular Pain, a Case Study Report of 5 Consecutive Cases 
Temporomandibular disorders (TMDs) represent a group of painful conditions involving the muscles of mastication and the temporomandibular joint. Ping On Ointment has been used in the Chinese Orthopedics as a soothing massage balm for muscular aches, strain and sprain. If topical application of the ointment can be effective for the treatment of TMD muscular pain, it may be the long-sought-after method for safe, simple, cheap, non-invasive, and effective treatment modality of TMD muscular pain. Purpose: This report documented a case study of the first five consecutive cases using this treatment modality.
All cases resulted in complete remission of pain within one month of topical massage.
This treatment method has high potential to benefit a significant number of people and randomized control trials should be performed.
PMCID: PMC2687118  PMID: 19506702
7.  Late onset systemic lupus erythematosus in southern Chinese 
Annals of the Rheumatic Diseases  1998;57(7):437-440.
OBJECTIVE—Systemic lupus erythematosus (SLE) is a multisystem disorder that predominately affects women of the reproductive age. Onset of the disease beyond the age of 50 years is unusual. This study was undertaken to compare retrospectively the clinical and laboratory features between early and late onset (onset of disease beyond the age of 50 years) SLE patients in a Chinese population.
METHODS—Case records of all SLE patients who attended our rheumatology clinics between 1971 and 1997 were reviewed. Patients with a disease onset beyond the age of 50 years were identified. One hundred consecutive SLE patients who had their disease onset before the age of 50 were recruited as controls. The presenting clinical features, autoantibody profile, number of major organs involved, number of major relapses, and the use of cytotoxic agents in the two groups of patients were obtained and compared.
RESULTS—25 patients with late onset SLE were identified. All the female patients in the late onset group were postmenopausal. The female to male ratio was 3.2 to 1, compared with 13.3 to 1 in the control group (p<0.02). Both groups had a comparable duration of disease. There were no significant differences in the presenting features between the two groups except for a lower prevalence of malar rash (24% v 86%, p<0.0001) and a higher prevalence of rheumatoid factor (32% v 1%, p<0.0001) in the late onset patients. On subsequent visits, the late onset group had a lower prevalence of lupus nephritis (4% v 51%, p<0.001), fewer major organs involved (mean number of major organs involved; 0.3 v 0.9, p<0.02), fewer major relapses (mean number of major relapses/patient; 0.08 v 0.47, p<0.002, number of major relapses/patient year; 0.009 v 0.12, p<0.001), and required fewer cytotoxic agents for disease control (percentage of patients on cytotoxic agents; 32% v 79%, p<0.002).
CONCLUSION—Late onset SLE in Chinese tends to run a more benign course with fewer major organ involvement and fewer major relapses. The significantly higher incidence of male sex in late onset SLE and the milder disease course in the postmenopausal female patients suggest that oestrogen status may influence disease activity.

 Keywords: systemic lupus erythematosus; southern Chinese; Asians
PMCID: PMC1752656  PMID: 9797573

Results 1-8 (8)